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MEDICAL TERMINOLOGY and THE HUMAN BODY

Lecture notes by Professor Mutombo Nkulu-N’Sengha

California State University Northridge, Los Angeles

TABLE OF CONTENTS

HOW MEDICAL TERMS ARE CONSTITUTED (GREEK AND LATIN)

LEXICON OF MAJOR BODY SYSTEMS

(Contains: A. terms; B. Diseases; C. Procedures)
and comprises 3 sections:
Overview
Basics
Odds and ends

Systems addressed here:

1. Circulatory system
2. Respiratory system
3. Nervous system
4. Digestive system

5. Urinary system
6. Male reproductive system
7. Female reproductive system
8. Musculoskeletal system
Musculoskeletal system diseases
Musculoskeletal system procedures
Musculoskeletal system medical record
9. The Brain
10. Cancer terms

MEDICINE CABINET (TERMINOLOGY FOR DRUGS)

BASICS

HOW MEDICAL TERMS ARE CONSTITUTED

Before we can start in with some new and interesting medical terms, you need to learn a few fundamentals of how
medical terminology is constructed as a language.

There are three basic parts to medical terms: root, prefix and suffix

a word root (usually the middle of the word and its central meaning), a prefix (comes at the beginning and usually
identifies some subdivision or part of the central meaning), and a suffix (comes at the end and modifies the central
meaning as to what or who is interacting with it or what is happening to it).
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It is worth noting that prefix and suffix changes can alter the meaning of a term without changing its central
meaning by keeping the root the same.

It is important to note that some words are polysemic. For instance, the Latin word for evil, “malum,” also means
apple. The Latin root is found in such words as malady and malignant.

An example of Word root:

therm = heat; hypothermia (less heat); thermometer (measuring heat)

Let’s look at a real medical term and take it apart.

Myocarditis
(prefix) (root) (suffix)
myo = muscle card = heart itis = inflammation
Don’t get blown away by that big, intimidating word! We haven’t introduced word roots yet. I just wanted to
demonstrate the major parts of a medical term.

Prefix change:

Myocarditis = muscle layer of heart inflamed

Pericarditis = outer layer of heart inflamed
Endocarditis = inner layer of heart inflamed
Suffix change:

Cardiologist = a physician specializing in the heart

Cardiomyopathy = damage to heart muscle layer
Cardiomegaly = enlargement of the heart
Again, we haven’t introduced heart terms yet. These basics are just to introduce the parts of medical terms and
demonstrate how moving the parts around modifies the central meaning without changing the “root” (cardio).

Useful Prefixes and Suffixes

Following, in no particular order, are frequently used word beginnings (prefixes) and word endings (suffixes) used
to make up many medical terms.

-itis = inflammation tonsillitis, appendicitis (you know these!)

-osis = abnormal condition cyanosis (of blueness, due to cold or low oxygen)
-ectomy = to cut out (remove) appendectomy, tonsillectomy (you know these too!)
-otomy = to cut into tracheotomy (to cut into the windpipe,
temporary opening)
-ostomy = to make a colostomy (to make a permanent opening in colon)
“mouth”
a/an = without, none anemia (literally no blood but means few red cells)
micro = small microstomia (abnormally small mouth, see “stomy” in colostomy above?)
macro = large macrostomia (abnormally large mouth)
mega/ -megaly = enlarged megacolon (abnormally large colon = large intestine)
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-scopy/ -scopic = to look, observe colonoscopy (look into colon)

Just a few more that you will see and hear over and over again.

-graphy/ -graph = recording mammography (imaging the breasts)

an image
-gram = the image (X-ray) mammogram
Whenever you see these endings, -graphy, -graph, -gram, they relate to recording an image such as an X-ray, CT or
MRI scan or a written recording with pen and moving paper. Mammography is the process of recording, i.e. the
machine and procedure. Mammogram is the image itself, the X-ray. A recording of heart activity is called an
electrocardiogram using an electrocardiograph. A recording of brain activity is an electroencephalogram and the
medical procedure and machine is called electroencephalography (whew, what a mouthful!).

-ology/ -ologist = study, specialize in cardiologist, nephrologist (study

the heart, the kidneys)
To see a lung specialist, you would visit a pulmonologist. To see a specialist in nerve and brain disease, make an
appointment with a neurologist. If you have a bad eye infection, you may be referred to an ophthalmologist. Your
rheumatism acting up? You would want to find a physician specializing in rheumatology.

Word Roots for Organs

Before we start learning specific medical terms for various systems of the body, we need to know word roots that
identify major organs in the body.

Stomato = mouth stomatitis

Dento = teeth dentist
Glosso/linguo = tongue glossitis, lingual nerve
Gingivo = gums gingivitis
Encephalo = brain encephalitis
Gastro = stomach gastritis
Entero = intestine gastroenteritis
Colo = large intestine colitis, megacolon
Procto = anus/rectum proctitis, proctologist
Hepato = liver hepatitis, hepatomegaly
Nephro/rene = kidney nephrosis, renal artery
Orchido = testis orchiditis, orchidectomy
Oophoro = ovary oophorectomy
Hystero/metro =uterus hysterectomy,
endometritis
Salpingo = uterine tubes hysterosalpingogram
Dermo = skin dermatitis
Masto/mammo = breast mammography, mastectomy
Osteo = bones osteoporosis
Cardio = heart electrocardiogram (ECG)
Cysto = bladder cystitis
Rhino = nose rhinitis (runny nose!)
Phlebo/veno = veins phlebitis, phlebotomy
Pneumo/pulmo = lung pneumonitis, pulmonologist
Hemo/emia = blood hematologist, anemia
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Note that some organs have more than one word root. Example: “masto” and “mammo”. Typically, one is derived
from the Greek and one from Latin. Go figure! But, you need to know both roots because you may see either of
them used.

The word ending “-itis” is going to be used repeatedly. It means inflammation, and I want to make sure you know
what that means. An infected cut is an inflammation. “Pink eye” is an inflammation. But, four things must be
present to define inflammation: pain, redness, heat and swelling (dolor, rubor, calor and tumor in Latin!). But,
inflammation of an internal organ such as the stomach or kidney must be defined by a physician relying on signs and
symptoms, and, possibly, the need for a biopsy (tissue sample) to examine under a microscope by a specialist in
identifying the causes of diseased tissues, a pathologist

Having clarified how words are composed, we now cover a few items that don’t fit into any particular system. Next,
we start organ systems!

Technicolor terms

Leuk/o = white leukemia (overabundance of white blood cells)

melan/o = black melanoma (black tumor of the skin)
cyan/o = blue cyanosis (blueness may be due to cold or not enough oxygen in blood)
xanth/o = yellow xanthoma (yellow tumor)
Tumor talk

Adding – oma (a swelling) to organ and tissue word roots names tumors. Not all tumors are malignant (cancerous).
Many are benign (not life-threatening).

Aden/o = gland adenoma

Lip/o = fat lipoma
My/o = muscle myoma
Lymph/o = lymph tissue lymphoma
Carcin/o = malignant carcinoma
Osteo/o = bone osteoma
Directions, please?

Endo = within, inside of endoscopy (to inspect the inside of an organ or space with a lighted instrument)
Peri = around perianal (around the anus)
Circum = around circumcise (cut around)
Retro = behind retrosternal (behind the breastbone)
Epi = upon, on top epidermis (the top or outermost layer of skin)
Trans = through transurethral (through the urinary exit duct)
Intra = within intravenous (inside the veins, e.g. IV fluids)
Sub = below subclavian (below the clavicle = collar bone)
In review, the word parts that make up medical terminology are prefixes, suffixes and word roots. The most typical
sequence is prefix, word root, suffix with the word root being central but this is not always the case. In the interests
of simplification, I have taken some liberties with formal construction, putting a hyphen in front of a suffix to
indicate it is added to the end of a word, example, -itis. Prefixes and word roots I have shown as freestanding word
parts. You may have noticed that sometimes I have added a slash and a vowel, example, melan/o. These are called
combining forms which make it easier to attach to other word parts, and, hopefully, making them easier to
pronounce. Just so you know!

Signs and symptoms : what’s the difference?

A symptom is something you observe and complain about to the physician. “Doctor, I have a fever”.
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A sign is something the physician observes and/or can measure.

LEXICON OF MAJOR BODY SYSTEMS

(Contains: A.terms; B. Diseases; C. Procedures)
and comprises 3 sections:
Overview
Basics
Odds and ends

Systems addressed here:

1. Circulatory system
2. Respiratory system
3. Nervous system
4. Digestive system

5. Urinary system
6. Male reproductive system
7. Female reproductive system
8. Musculoskeletal system
Musculoskeletal system diseases
Musculoskeletal system procedures
Musculoskeletal system medical record
9. Cancer terms

MEDICINE CABINET (TERMINOLOGY FOR DRUGS_

1. Circulatory System

Circulatory system terms

Cardi/o = heart Endocarditis, myocarditis, pericarditis (inflammation of the lining,

the muscle layer, the outer layer of the heart)
Brady/tachy = slow/fast Bradycardia (rate<60) tachycardia (rate>100)
Angi/o = vessel Angiography, angiogram (X-ray of artery)
Veno/phlebo = vein Venogram (X-ray of veins), phlebitis (inflammation of veins)
-stasis = to stop Hemostasis (to stop bleeding), hemostat (a clamp-like instrument)
-cyte = cell Erythrocytes, leucocytes (red, white blood cells)
Hem/o, -emia = blood Hypoxemia (low oxygen), hematosalpinx (blood in the uterine tubes)

Circulatory System Diseases

Atherosclerosis– Literally, “hardening of the fatty stuff.” High fat diets can lead to formation of fatty plaques lining
blood vessels. These fatty areas can become calcified and hard leading to arteriosclerosis, hardening of the arteries.
When blood vessels become less stretchable, blood pressure rises and can result in heart and kidney damage and
strokes. Double cheese bacon burger, anybody?
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Myocardial infarction (MI)– You know we are talking about heart muscle, right, myocardial? An infarction is
blockage of blood flow resulting in death of muscle tissue. Layman’s language for this is a “heart attack.” The
blockage occurs in one of the arteries of the heart muscle itself, a coronary artery. Depending upon how much tissue
dies, a victim of an MI may survive and undergo cardiac rehabilitation, strengthening the remaining heart muscle, or
may die if too much muscle tissue is destroyed. Did you exercise at the gym this week?

Mitral prolapse, stenosis, regurgitation– Blood flows through four chambers in the heart separated by one-way
valves. A major valve is the one separating the upper and lower chambers on the left side of the heart. The left side
is especially important because freshly oxygenated blood returning from the lungs is circulated out of the heart to
the rest of the body. The left valve, called atrioventricular, for the chambers it separates, is also called the mitral
valve, because it is shaped like an upside down Bishop’s hat, a miter. If the flaps of this valve tear away due to
disease, the process is called prolapse, “a falling forward.” This results in leakage and backward flow called
“regurgitation” (get the picture?). Sometimes a valve is abnormally narrow causing partial obstruction constricting
flow. Stenosis means “a narrowing.”

Angina pectoris– Literally, “pain in the chest.” But, this is a special kind of pain associated with the heart and is
distinctive as “crushing, vise-like”, and often accompanied by shortness of breath, fatigue and nausea. Anginal pain
indicates not enough blood is getting to the heart muscle, and the heart is protesting and begging for more. People
with a history of angina often take nitroglycerine tablets to relieve the pain by increasing blood flow to the heart
muscle.

Arrhythmia, dysrhythmia, and Ischemia

(Doctor listening to a patient's heartbeat")

Abnormal heart rates and rhythms all have special names like ventricular tachycardia, fibrillation, but generically are
termed arrhythmias or dysrhythmia, meaning “no rhythm” and “abnormal rhythm.”

There are fine distinctions between the two, but they are often used interchangeably.

Ischemia– Sometimes the heart muscle is not getting enough blood flow, more importantly, the oxygen the blood
carries is insufficient to sustain muscle which has a very high metabolic rate, and oxygen demand. The term loosely
means “not quite enough blood.” Typically, the patient suffers angina pain (see above) and they may think they are
having a heart attack. And, they may be!

Circulatory System Procedures

Cardiologist – a physician specializing in the diagnosis and treatment of diseases of the circulatory system,
especially, the heart. However, after diagnosis, he/she may refer to a cardiovascular surgeon. A cardiologist does not
do surgery.

Hematologist – a physician specializing in diseases of the blood.

Electrocardiogram (ECG/EKG) – a printout recording of the electrical activity of the heart. A frequently used
instrument in the hands of a cardiologist.

Echocardiography – using ultra high frequency sound waves (beyond human hearing), similar to “sonar,” to form
an image of the inside of the heart. This procedure can demonstrate valve damage, congenital (before birth) defects
and other abnormalities.

Cardiac catheterization – a long hollow tube, a catheter, can be threaded into an artery up into the heart. Then
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material opaque to X-rays can be released into the blood flow through the heart imaging the details of coronary
arteries. Typically used to identify a blockage and location in the coronary circulation.

Phlebotomist/venipuncturist – the specially trained nurse or technician draws blood for lab tests and may also start
IV’s (intravenous fluids). The Greek and Latin versions of “cutting into a vein.”

2. Respiratory System

Respiratory system terms

Rhin/o Nose Rhinitis, rhinorrhea (inflammation of and “runny” nose)

Laryng/o Larynx, “voice box”* Laryngotomy, Laryngectomy (cutting into, surgically removing the larynx)
Trache/o Trachea, “windpipe” Tracheotomy, tracheostomy (temporary and permanent openings)
Bronch/o Lung air passageways Bronchoscopy (looking into the bronchi)
Pne/u, -pnea Breath, air, lung Tachypnea, dyspnea, apnea (accelerated, difficult/painful, cessation of breathing)
Pulmo/o Lung Pulmonary artery
-ptysis Spitting (coughing) Hemoptysis (spitting or coughing up blood from lungs)
-plasty Reconstruction Rhinoplasty (surgical reconstruction of nose)

*Adam’s apple – Everyone is familiar with the bulge in the front of the neck we call an ‘Adam’s apple.’ This
structure, termed the laryngeal prominence, is a cartilage in the ‘voice box’ or larynx. Testosterone, the male
hormone, enlarges the larynx in males which also lengthens the vocal cords lowering the voice at puberty.

Respiratory System Diseases

Pneumoconiosis – literally, “an abnormal condition of dust in the lungs.” A generic name for conditions where
toxic particles become trapped in the lungs and cause symptoms and disability such a “black lung” or “miner’s lung”
disease. Terms specific to the particulate matter may be given such as asbestosis.

Epistaxis – want a fancier name for a “nosebleed?” You got it!

Cystic fibrosis – an inheritable disease that affects not only the lungs but other systems producing mucous such as
the digestive system. Patients suffer frequent lung infections that are hard to treat because mucous is thick and
sluggish and result in increased scarring (fibrosis) of the lungs. They also take multiple enzyme pills because of
digestive abnormalities related to abnormal mucous production.

Emphysema (COPD) – Chronic Obstructive Pulmonary Disease, of which emphysema is one of, results in
progressive destruction of the air sacs in the lungs and loss of respiratory membrane for oxygen exchange. The bane
of long term smokers.

Atelectasis – a collapsed lung. Literally, “an imperfect expansion” in Greek.

Respiratory System Procedures

Pulmonologist – a physician specializing in diseases of the lungs. Patients needing surgery are referred to a general
surgeon.

Pulmonary angiography – special X-rays of the vessels of the lungs.

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Laryngoscopy – visual examination of the larynx.

Endotracheal intubation – passing a special air-tube into the trachea so oxygen can be reliably supplied directly to
the lungs without risk of inhaling vomit from the stomach. Typically done for surgery or whenever general
anesthesia is administered among other situations where the patient’s airway must be secured.

3. Nervous System

Nervous system terms

Cephal/o Head Cephalgia (a headache)

Encephal/o Inside the head (brain) Encephalitis (inflammation of the brain) Anen
brain)
Mening/o Membranes surrounding the brain and spinal cord Meningitis (inflammation of the membranes)
Myel/o Spinal cord Myelogram (X-ray of the spinal cord)
Neur/o Nerve Neuroma (tumor) Neuritis (inflammation)
Dys Difficult, painful, abnormal Dyslexia (difficulty reading)
-cele Hernia, abnormal protrusion of structure out of normal Meningomyelocele (protrusion of membranes
anatomical position
-pathy Disease, abnormality Encephalopathy (disease of the brain) Neurop
nerves)
-plasia Development, formation, growth Aplasia (no development) Hyperplasia (over d
-plegia Paralysis Hemiplegia (paralysis of one side of the body
of all four limbs)

Nervous System Diseases

Multiple Sclerosis – Literally, “many hardenings,” MS is a disease of unknown cause that manifests as multiple
hard plaques of degeneration of the insulating layer of nerve fibers in the central nervous system. The loss of
insulation allows “short circuiting” of nerve impulses. Depending upon where the degeneration occurs, patients may
suffer paralysis, sensory disturbances or blindness.

Cerebrovascular accident (CVA) – the fancy name for a “stroke”. A blood vessel in the brain may burst causing
internal bleeding. Or, a clot may arise in a brain blood vessel (a thrombus), or arise elsewhere (embolus) and travel
to get stuck in a brain vessel which then deprives brain tissue of oxygen. Depending upon the area of the brain
involved, the patient may suffer paralysis, loss of speech or loss of vision.

Transient Ischemic Attack (TIA) – “Ischemia” was introduced previously in the circulatory diseases module
referring to the heart. It literally means “not quite enough blood”. A short period of insufficient blood supply to the
brain can have the same signs and symptoms as a stroke such as weakness in an arm, a partial loss of vision, but the
problem lasts less than 24 hours. People who get TIA’s are at increased risk of having a stroke in the future.

Epilepsy – a Greek word for “seizure.” Convulsions is another term used. Seizures may have many causes and not
all seizures are epilepsy. High fevers in young children may trigger seizures which are short in duration, easily
controlled and, typically, have no permanent aftereffects. Epilepsy is a specific condition which may occur at any
age, seizures are more intense, longer lasting in duration, and recur with some frequency. The condition may be
controlled with medication, or if unresponsive to drugs, may require surgery.

Aphasia – loss of speech. The speech centers are located on the left side of the brain in a majority of people. If
someone suffers a “stroke” (cerebrovascular accident-CVA), or traumatic brain injury, and it involves the left side of
the brain, they may suffer speech impediments that vary over a spectrum of problems from difficulty in finding the
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right word, speaking slowly and with difficulty, or complete loss of speech. Actually, there are two speech centers.
Injury described above involves the motor speech area, the area of the brain that produces language by integrating
thoughts of speech with the movements of the larynx, lips and tongue. There is a second speech area, the receptive
or sensory area, that enables us to understand speech. Injury to the latter results in still fluent speech, but the
individual does not understand what they are hearing.

Nervous System Procedures

Neurologist – a physician specializing in diseases of the brain, spinal cord and nerves. He/she may refer a patient to
a neurosurgeon. Neurologists do not do surgery.

Lumbar (spinal) puncture or tap (LP) – introducing a needle between the lower bony vertebrae of our spinal
column allows a physician to sample the fluid, cerebrospinal fluid (CSF), surrounding the brain and spinal cord. Lab
tests on the fluid are used for diagnostic purposes such as presence of bacteria in meningitis, special proteins in
multiple sclerosis, or blood cells.

Brain scan – introducing a radioactive element into the blood can image possible tumors in the brain. The
radioactive dose is very low and detectable only with special, very sensitive instruments that are much more
sophisticated than the old Geiger counters.

Electroencephalography (EEG) – Wow, what a mouthful, but take it apart. Starting at the end of the word: an
image (in this case a written recording) of the brain’s electrical activity. EEGs are used to diagnose different types of
seizure disorders such as epilepsy, brain tumors, and are used in sleep research to identify stages of sleep.

Computed tomography (CT) – a specialized X-ray machine that takes multiple images of a body area from
different angles and has a computer that integrates the multiple images into “slices” of the body. The resolution is
much better than standard X-rays and there is better differentiation of types of tissue (bone, air, solid organ).

Magnetic Resonance Imaging (MRI) – Although the image produces the “slices” through the body seen by CT
(see above), no X-rays are involved. The patient’s body is placed in a strong magnetic field. Radio pulses affect the
resonance or “spin” of atoms in the tissues. A computer analyzes this information to show subtle differences in
tissue molecular structure producing very high resolution and better differentiation of soft tissue, such as a tumor
within the liver.

4. Digestive System
Digestive system terms

Gastr/o Stomach Gastritis, Gastrectomy

Hepat/o Liver Hepatitis (inflammation of), hepatoma (tumor of)
Chol/e Gall, bile Cholecystitis, cholecystectomy (inflammation of, removal of gallbladder)
Cyst/o Bladder, sac (see above)
Emes/o Vomit Emesis (vomiting), emetic (stimulating vomiting), antiemetic (stopping vomiting)
Lith/o Stone Cholelithotomy (removal of gall stones)
Lapar/o Abdominal wall Laparotomy (cutting into the abdomen)
-centesis To puncture Abdominocentesis (puncturing and draining)
-tripsy To crush Cholelithotripsy (smashing gall stones with sound waves)
-rrhea Flow, discharge Diarrhea
-iasis Abnormal condition Cholelithiasis (presence of gall stones causing symptoms)
(-osis)
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Digestive System Diseases

Gastroesophageal Reflux Disease (GERD) –Severe “heartburn” in laymen’s language. Weakness of the valve
between the esophagus and stomach may allow stomach acid to reflux (regurgitate, backup) into the esophagus and
irritate and inflame the lining. This results in chest pain which can mimic that of angina (pain of cardiac ischemia or
an MI).

Jaundice – Literally means “yellow” in French. Yellowing of the skin and whites of the eyes from a backup of bile
metabolic by-products from the blood into body tissues. May result from blockage of the ducts draining bile from
the liver into the intestines or excessive breakdown of red blood cells. Hemoglobin from destroyed RBCs is broken
down, and in part, ends up in bile secretions.

Diverticulosis/diverticulitis – Small pouches may form along the walls of the large intestine called diverticuli
which if symptomatic, causing discomfort to the patient, is called diverticulosis. These abnormal outpocketings may
collect and not be able to empty fecal material which can lead to inflammation, diverticulitis.

Cirrhosis – Literally, “orange-yellow” in Greek. A degenerative disease of the liver that often develops in chronic
alcoholics, but can have other causes. The name refers to the gross appearance of the organ.

Portal hypertension – A potential complication of chronic alcoholism resulting in liver damage and obstruction of
venous blood flow through the liver. The rising blood pressure in the veins between the gastrointestinal tract and
liver causes engorgement of veins around the umbilicus (navel). The characteristic radiating pattern of veins is
called a “caput medusae” (head of Medusa). Medusa was the “snake-haired lady” in Greek mythology.

Esophageal varices – bulging, engorged veins in the walls of the esophagus are often a complication of chronic
alcoholism (see portal hypertension). The thin-walled, swollen veins are at risk of tearing resulting in severe,
possibly fatal, bleeding.

Dysphagia – Difficulty swallowing. May be related to GERD (see above), esophageal tumor or other causes.

Crohn’s Disease – a chronic inflammatory disease primarily of the bowel. Typical symptoms are abdominal pain,
weight loss, diarrhea. There may also be rectal bleeding that can lead to anemia. Special X-rays and tests are needed
to differentiate Crohn’s from other diseases with similar symptoms.

Peritonitis – Inflammation of the lining of the abdominal cavity. Before antibiotics, people would die from
peritonitis if an inflamed appendix burst. Indications of peritonitis are called “peritoneal signs”: tender abdomen,
rebound pain (pain when manual pressure released from examining abdomen), board-like rigidity of abdominal
muscles, no bowel sounds (gurgles). The peritoneal membrane is very sensitive to exposure to foreign substances.
Contact with blood, bile, urine, pus will cause peritoneal signs.

Digestive System Procedures/specialists

Gastroenterologist – a physician specializing in diseases of the digestive system including esophagus, stomach and
intestines. These specialists do not do surgery. Patients needing surgery are referred to a general surgeon.

Proctologist – a physician specializing in diseases of the rectum and anus. Proctology is a surgical subspecialty.

Guaiac test (Hemoccult, Fecult) – a special chemical test to identify blood in the stool (feces). Blood in the stool
may have many causes including cancer and hemorrhoids.

>Upper GI series – a series of X-rays of the esophagus and stomach and small intestines having the patient swallow
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a “milkshake” of barium. The element barium is opaque, i.e. blocks , X-rays. This procedure may be used to identify
problems with swallowing, stomach ulcers, twisting of the small intestines.

Lower GI series – a series of X-rays using a barium enema to show the large intestine and rectum. This procedure
can be used to identify problems such as diverticulitis/diverticulosis, and tumors.

Endoscopy – use of a flexible fiberoptic instrument attached to a video camera that can be used to directly visualize
the esophagus, stomach and large bowel. Special names may be used for each area explored such as colonoscopy.

Ultrasonography (ultrasound) – a procedure using high frequency sound waves to visualize internal organs.
Primarily used to visualize abdominal and pelvic organs, such as the pregnant uterus.

Digestive System Medical Record

You should be getting pretty good at making sense of medical terminology. But, nothing beats practical application!
Following is an abstract of a simulated patient’s medical record. Note words in italics. Take them apart. Look for the
“root” meaning. Read the record and answer the questions that follow to yourself. If you can’t think of the meaning,
hover your cursor over the word for a tip.

A 48 year old male complains of abdominal discomfort after meals, especially, high fat meals. At those times he
also has aching in his right shoulder and back. An ultrasound of the upper abdomen revealed cholelithiasis. A
consult with a gastroenterologist determined that cholelithotripsy was considered but it was decided that
a laparoscopic cholecystectomy would be the first procedure attempted. If complications were encountered then
an open cholecystectomy would be performed.

Significant medical history: patient had a coronary angiography performed at age 46 following
suspected myocardial infarct.

What is the diagnosis (the patient’s current medical problem)?

Did the procedure performed to aid in the diagnosis involve use of X-rays?
Was a specialist appropriate to the diagnosis consulted?
What treatments were considered?
What significant event was in the patient’s medical history?
What procedure was performed in the patient’s medical history?
In plain English

A 48-year-old male complains of abdominal discomfort after meals, especially, high fat meals. At those times he
also has aching in his right shoulder and back. A procedure using high frequency sound waves to image the upper
abdomen revealed stones in the gallbladder. A consult with a specialist in diseases of the digestive tract determined
that crushing the gallbladder stones with sound waves was considered but it was decided that a removal of the
gallbladder using a scope and instruments inserted into the abdominal wall would be the first procedure attempted. If
complications were encountered then opening up the abdomen and removing the gallbladder would be performed.

Significant medical history: The patient had a heart attack. The patient’s heart arteries were imaged by injecting a
dye opaque to X-rays into an artery to show area of blockage of blood flow to heart muscle.

Surprised at how much you understood? I’m not!

Before taking the quiz, you may want to check back to “Basics” and review the word stems for mouth, tongue,
gums, stomach, small and large intestines and liver.
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5. Urinary System

Urinary system terms

Nephr/o, ren/o Kidney Nephritis, renal artery

Hydro/o Water Hydronephrosis (abnormal condition involving
back up of urine into the kidney
Cyst/o Bladder Cystitis, cystectomy (inflammation of,
removal of bladder)
Pyel/o Renal collecting ducts Pyelogram (X-ray of the collecting ducts)
Ur/o, -uria Urine Polyuria, anuria (frequent urination,
no urine formation)
Olig/o Scanty, less than normal Oliguria (reduced urine formation)
-pexy To surgically reattach, fix in normal position Nephropexy (surgically attach kidney
in normal anatomical position)

Urinary System Diseases

Nephrolith – a kidney stone.

Urethritis – inflammation of the urethra, the final pathway for urine in both sexes, and the common pathway for
urine and semen in the male.

Nocturia – frequently getting up and urinating during the night.

Enuresis – involuntary release of urine, most often in reference to “bedwetting.”

Urinary System Procedures

Nephrologist – I am hoping by now, you would know this is a physician specializing in kidney diseases.

Urologist – a physician specializing in the genitourinary tract, which includes kidneys, urinary bladder and urethra
of both men and women and the prostate and testes in men.

Cystoscopy – looking into the urinary bladder with a fiberoptic instrument.

Intravenous pyelogram – special X-rays showing the drainage pattern of the kidneys. A dye opaque to X-rays is
injected into a vein. After a waiting period for the blood and dye to pass through the kidneys, X-rays can be taken of
the collecting system of the kidney, ureter and bladder.

Retrograde pyelogram – personally, I prefer the former procedure! In this procedure a dye opaque to X-rays is
flushed backwards up the urethra and bladder and up the ureters to the kidneys.

Voiding cystourethrogram – take this apart starting at the end of the word: an imaging technique (X-ray)
displaying the urethra and bladder while urinating! How did the opaque dye get into the bladder? One guess then see
retrograde pyelogram above.

Dialysis – a procedure for cleansing the blood of waste products in individuals with complete kidney failure or who
have had kidneys removed by surgery. With the in-hospital procedure, the patient’s blood is circulated through a
machine that removes waste products. The blood is recirculated back into the patient.
 13

Lithotripsy – Crushing kidney stones with sound waves. Unlike cholelithotripsy (crushing of gallstones), which is
no longer done, the sludge from crushing kidney stones has an easy direct pathway out of the body (down the ureter
to the bladder and out the urethra). Nephrolithotripsy is an elective procedure that may spare a patient surgery.

6. Male Reproductive System

Male reproductive system terms

Orchid/o, test/o Testes (male gonad) * Orchiditis, orchidectomy, testicular artery, testosterone (male sex hormone)
Balan/o Head of the penis Balanitis
Andr/o Male Androgenic (stimulating maleness), androgynous (characteristics of male and female a
Prostat/o Prostate Prostatitis, prostatectomy
Vas/o Vessel, duct Vas deferens, vasectomy (duct carrying semen from testes, cutting the duct)
-rrhaphy To suture Herniorrhaphy (surgical correction of inguinal hernia)
*Testis – Did you know that testis, testify, testimonial and testament all share a common root meaning? Testis
means “witness” in Latin. As the testis witnesses to manhood, you may witness to the truth at trial, proclaim your
favorite brand of corn flakes or witness to your final wishes in your will. If you die without a will, you die
“intestate,” without having witnessed.

Male Reproductive System Diseases

Hypospadias – literally “below the fleshy spike.” A condition in which the external urinary meatus (opening) opens
anywhere below the tip of the penis rather than at the tip.

Hydrocele – a fluid filled sac partially surrounding the testis. Manifests itself as a swelling on the side of the
scrotum. May cause discomfort. Can be surgically corrected. And, who would most likely be doing the surgery? A
urologist!

Varicocele – dilated and twisted veins of the testis, sort of “hemorrhoids” of the scrotum! Manifests itself as a
swelling on the side of the scrotum which may look and feel like a “bag of worms.” May be surgically corrected if
causing discomfort. This condition may also cause reduced sperm count and male sterility due to sluggish blood
flow elevating testicular temperature.

Cryptorchidism – literally “hidden testicle.” A condition of lack of descent of one or both testes into the scrotum. If
not corrected, usually by surgery, before puberty, can lead to sterility and increased risk of testicular cancer.

Benign prostatic hypertrophy (BPH) – swelling of the prostate gland which surrounds the base of the male
bladder and urethra causing difficulty urinating, dribbling, and nocturia (remember that word? See urinary system).
The bane of old men! BPH becomes more common as men age.

Transurethral resection of the prostate (TURP) – the surgical cure for BPH. An instrument inserted through the
penile urethra is used to partially cut away the prostate to relieve obstruction of the urinary tract.

Prostate Specific Antigen (PSA) – PSA is a marker protein for prostate cell secretions which can be detected with a
lab test. A rising PSA may be an early sign of prostate cancer, although there may be other causes including false
positive tests. How often should men get a PSA test? Check in with The Prostate Cancer Foundation.

Male Reproductive System Medical Record

Following is an abstract of a simulated patient’s medical record. Read the record and define each term in italics. If
you can’t think of the meaning, hover your cursor over the word for a tip.
 14

A 55 year old male complains of nocturia, three to four times a night.He also states that he has difficulty getting
urination started, has a small stream, and dribbles after he finishes. Sometimes he has feelings of urgency. A review
of organ systems reveals that his angina, which he treats with nitroglycerine tablets, is increasing in frequency.

A rectal exam reveals prostatic hypertrophy without nodules, most likely BPH. Patient was scheduled for an ECG
and coronary angiography. A referral was made to a urologist for evaluation for a TURP.

Recent medical history: hemoptysis two months ago. Bronchoscopy was unremarkable.

Past medical history: cholelithiasis treated with cholelithotripsy at age 52. Varicocelectomy at age 28.
Appendectomy at age 24.

In plain English

A 55 year old male complains of having to get up at night to urinate, three to four times a night. He also states that
he has difficulty getting urination started, has a small stream, and dribbles after he finishes. Sometimes he has an
urgent need to urinate. A review of organ systems reveals that his cardiac related chest pain, which he treats with
nitroglycerine tablets, is increasing in frequency.

A rectal exam reveals an enlarged prostate without nodules, most likely Benign Prostatic Hypertrophy (nonlife-
threatening enlargement of the prostate). Patient was scheduled for an electrocardiogram (recording of the electrical
activity of the heart) and X-rays of the arteries of the heart. A referral was made to a specialist in diseases of the
male reproductive system and lower urinary tract for possible transurethral resection of the prostate (partial internal
removal of prostatic tissue).

Recent medical history: spitting up blood from the lungs two months ago. Passing a fiberoptic instrument into the
lung passageways did not determine a cause.

Past medical history: gallstones treated with high frequency sound waves smashing stones to small particles that can
pass in the stool at age 52. Removal of enlarged testicular veins at age 28. Removal of appendix at age 24.

Reproductive System Mythology

Greek and Roman mythology is alive and well!

Term Description God/godess

Hymen Membrane surrounding entrance of vagina Hymen – the Greek god of marriage
Aphrodisiac A chemical purported to stimulate sexual desire Aphrodite- The Greek goddess of love
Venereal disease A sexually transmitted infectious disease Venus – the Roman goddess of love
Hermaphroditism A condition where both ovarian and testicular tissue are Hermaphroditus* – the offspring of Herm
found in the same individual looked female but had male genitalia
Priapism A continuous, painful erection Priapus – the Roman god of male potenc
Satyriasis A condition of compulsive sexual desire in men. Satyr- a woodland deity part man and par
chasing nymphs.

In Greek mythology, Hermaphroditus was the son of Hermes, messenger of the gods, and Aphrodite, the goddess of
love. He was a handsome young man. One day while swimming in a woodland pool, one of the Naiads, nymphs of
wells, springs and ponds, spied him and instantly fell in love with him. She swam out to him, embraced him
professing her love. He rejected her advances. Angry at being rejected, she prayed to the gods that they never be
separated again. The ancient gods had a whimsical, sometimes cruel, sense of humor and bound their bodies into
one, ever inseparable. Be careful what you ask for? The curse of the answered prayer?

In classic art, Hermaphroditus is portrayed as a woman with male genitalia. True hermaphrodites exist, although
they are rare, but most commonly have a male-type body with ambiguous genitalia. Internally, both ovarian and
 15

testicular tissue are present either as separate organs or an ovotestis. Related sex structures are poorly developed or
absent.

7. Female Reproductive System

Female reproductive system terms

Hyster/o, metr/ Uterus Hysterectomy, endometritis (inflammation of the lining of uterus)

Salping/o, -salpinx Uterine tube Salpingitis, hematosalpinx (blood in the uterine tube)
Colp/o Vagina Colporrhaphy (suturing a tear), colpoplasty (surgical reconstruction), colposcopy (v
Oophor/o Ovary Oophorectomy, oophoropexy (surgery fixation, reattachment)
Men/o Menstruation Menarche (first), dysmenorrhea (painful menstruation)
Mamm/o, mast/o Breast Mammogram, mastectomy
-pareunia, coitus Intercourse Dyspareunia (painful intercourse), precoital, postcoital (before and after intercourse

Female Reproductive System Diseases

Endometriosis – a condition involving colonization of the abdominal/pelvic cavity with islands of endometrial
tissue. Endometrium is the lining layer of the uterus which sloughs off with each menstruation. If endometrial tissue
flushes up the uterine tube and spills into the abdomen (peritoneal cavity), the clots of endometrial tissue can attach
to abdominal organs such as the bladder, rectum, intestinal loops and then cycle along with the uterus in response to
monthly changes in ovarian hormones. Bleeding into the abdomen irritates the lining membrane, the peritoneum,
and causes abdominal pain.

Pelvic inflammatory disease (PID) – although males have a closed abdominal cavity, the female abdominal cavity
has a direct anatomical path from the outside world via the female reproductive tract. Bacteria can make their way
up the vagina, through the uterus, and traverse the uterine tubes which open into the abdominal cavity. Inflammation
of the lining of the abdominal cavity, the peritoneum, causes abdominal pain. Although there are many potential
causes of PID, gonorrheal infection is one of them. Chronic Inflammation of the uterine tubes can occlude them
resulting in infertility.

Prolapsed uterus – the uterus is almost directly above the vagina. In fact, the cervix, the neck region, of the uterus
extends into the upper vagina. Ligaments hold the uterus in proper position so that it does not prolapse or herniate
into the vagina. Severe prolapse can result in the uterine cervix protruding from the vaginal opening. Surgical repair
is typically required to restore the uterus to its proper anatomical position.

Female Reproductive System Procedures

Obstetrician – literally “midwife” in Latin. A physician specializing in the diagnosis and management of pregnancy
and delivering babies.

Gynecologist – a physician specializing in diseases of the female reproductive system and surgery of this area. Most
physicians currently specialize in combined practice of OB/GYN.

Episiotomy – a surgical procedure cutting into the perineal area, the area between the vagina and anus in order to
prevent tearing of tissues when the baby’s head traverses the vaginal opening.

Hysterosalpingogram – special X-rays of the uterus and uterine tubes involving passing an opaque dye backwards
up through the uterus to determine if the tubes are patent. Since the tubes are open into the abdominal (peritoneal)
 16

cavity, if patent, dye should spill out of the end of the tubes and be manifest on the X-ray.

Colposcopy – using a magnifying instrument to inspect the interior of the vagina and cervix, the entrance to the
uterus.

Dilation and curettage (D & C) – dilating the cervix, the entrance into the uterus, and passing instruments that
enable scraping off superficial layers of the endometrium. May be done as an early therapeutic abortion, or
following a normal pregnancy to remove residual tissue remaining in the uterus, or may be done as a diagnostic
procedure to examine lining tissue of the uterus.

Mammoplasty – Surgical reconstruction of the breast may involve breast enlargement or reduction or cosmetic
reconstruction after mastectomy. What are the risk factors of developing breast cancer? Check out this women’s
health link for answers.

Pudendal block – An anesthetic administered to block sensation around the lower vagina and perineum. This
facilitates performing an episiotomy (see above) allowing passage of the baby’s head while avoiding uncontrolled
tearing of tissues. By the way, pudendal, an ancient name for external genitalia, means “that which we should be
ashamed of” in Latin. Even Adam and Eve wore fig leaves!

Female Reproductive System Terms of Pregnancy

-gravida Pregnancy Nulligravida (never pregnant), primigravida (first-time pregnant), multigravid

-para Live birth Nullipara (no live births), multipara (many live births)
Part/o, toc/o Labor/birth/delivery Prepartum, postpartum (before and after delivery), dystocia (difficult delivery)
EXAMPLE: On an OB patient’s chart you may see the abbreviations: gravida 3, para 2. This means three
pregnancies, two live births. The OB patient, currently pregnant with her third baby, will become a Gravida 3, Para
3 after giving birth.

Complications of pregnancy

Abruptio placentae– (Latin, “breaking off”). Premature separation of a normally implanted placenta before full
term. Occurs in only about 1% of pregnancies. However, it has a 20-40% fetal mortality rate and is a significant
contributor to maternal mortality.

Placenta previa– (Latin, “leading the way”). A placenta implanted over the cervical region of the uterus blocking
the entrance to the birth canal. Occurs in less than one percent of pregnancies, but can cause significant bleeding and
require a complicated delivery.

Eclampsia (toxemia of pregnancy )- a serious and life-threatening condition that may develop during pregnancy
involving hypertension, convulsions and coma. A less severe form, preeclampsia, may develop but can be managed
if identified and treated early.

Ectopic pregnancy– (Greek, “out of place”). A pregnancy implanted anywhere outside of the uterus. The uterine
tube (Fallopian tube) is the most common location, also called a “tubal pregnancy”. The abdominal cavity is the
least common location. Occurs in about 2% of pregnancies. When it occurs, it is a surgical emergency, because the
uterine tube cannot sustain tremendous expansion like the uterus. Eventually, the uterine tube will rupture with
severe, possibly fatal, hemorrhaging.

8. Musculoskeletal system
 17

Musculoskeletal system terms

Oste/o Bone Osteitis, osteoma, osteocyte

Chondr/o Cartilage Chondritis, chondroma, chondrocyte
Arthr/o Joint Arthritis, arthroplasty
Myel/o Bone marrow Myeloma
Ten/o, tendin/o Tendon (binds muscle to bone) Tendonitis, tenorrhaphy
Ligament/o Ligament (binds bone to bone) Ligamentous injury
Burs/o Bursa, “bag”, (shock absorber between tendons and Bursitis
bones)
My/o, myos/o Muscle Myoma, myositis
-malacia Softening Osteomalacia, chondromalacia
-porosis Porous Osteoporosis
-asthenia Weakness, loss of strength Myasthenia gravis
-trophy Development, stimulation, maintenance Atrophy (shriveling of muscles), hypertrophy (increas
muscles)
-algia, algesia Pain Myalgia, arthralgia, analgesia (take away pain
I have long since stopped defining what “-itis” means, or “-oma.” Do you remember what “-plasty” means, or how
about “-rrhaphy”? These word parts were introduced in previous modules. This program is all about building word
roots, prefixes and suffixes into medical terms. The ultimate goal is for you to be able to figure out the meaning of
new terms, or, at least, not be intimidated about looking it up in a medical dictionary.

Musculoskeletal System Diseases

Arthritis – As we age, our joint tissues become less resilient to wear and tear and start to degenerate manifesting as
swelling, pain, and oftentimes, loss of mobility of joints. Changes occur in both joint soft tissues and the opposing
bones, a condition called osteoarthritis. A more serious form of disease is called rheumatoid arthritis. The latter is an
autoimmune disease wherein the body produces antibodies against joint tissues causing chronic inflammation
resulting in severe joint damage, pain and immobility.

Osteoporosis – “Porous bone.” The bane of the old, especially, women. The hard, rock-like quality of bone is
dependent upon calcium. When too much calcium is dissolved from bones or not enough replaced, bones lose
density and are easily fractured. Estrogen, the female sex hormone, helps maintain proper calcium levels in bones.
Once the ovaries stop producing the hormone, women are at higher risk of developing osteoporosis. A collapse of
bony vertebrae of the spinal column results in loss of height and stooped posture. Hip fractures are a common
occurrence.

Osteomalacia – “Soft bones.” If not enough calcium is deposited during early childhood development, the bones do
not become rock-hard, but rubbery. Both adequate calcium in the diet and vitamin D, primarily, from normal
sunlight exposure or supplementation, are necessary for normal bone development. Before vitamin supplementation
to milk, “rickets,” another name for osteomalacia in children, was common resulting in the classic bowed legs of the
afflicted child.

Carpal tunnel syndrome – People whose job involves repeated flexing of their wrist (typing, house painting) may
develop tingling and/or pain in their thumb, index and middle fingers along with weakness of movements of the
thumb, especially, grasping an object. The main nerve for finely controlled thumb movements passes through a
bony/ligamentous canal on the bottom of the wrist. Repetitive flexing movements may inflame and thicken the
ligament over the “tunnel” through the carpal (wrist) bones trapping and compressing the nerve.

Tendonitis– Repeated strain on a tendon, attachment of a muscle to bone, can inflame the tendon resulting in pain
and difficulty with movement involving the muscle. Tendons have a poor blood supply; therefore, they typically
take a long time to heal on the order of six weeks or more.
 18

Rotator cuff tear – Muscles surrounding the shoulder joint are involved in rotating the shoulder with upper arm and
hand forward and backward, among other movements. The tendons of these muscles also contribute to the structural
strength of the shoulder joint. Hard, fast movements, such as in tennis and baseball can tear one of these tendons
resulting in pain and decreased mobility of the shoulder. Surgery may be needed to repair a torn tendon.

Bursitis – A bursa is a small, closed bag with a minimum amount of lubricatory fluid that serves as a shock absorber
where bones make close contact and to minimize trauma and friction where tendons cross bones and joints.
Inflammation leads to pain and immobility in a joint area.

Muscular dystrophy – Muscular dystrophy is a group of inherited diseases in which the muscles that control
movement progressively weaken. The prefix, dys-, means abnormal. The root, -trophy, refers to maintaining normal
nourishment, structure and function. The most common form in children is called Duchenne muscular dystrophy and
affects only males. It usually appears between the ages of 2 to 6 and the afflicted live typically into late teens to
early 20s.

Myasthenia gravis – “Muscular weakness, profound”. This is an autoimmune disease that involves production of
antibodies that interfere with nerves stimulating muscle contractions. Face and neck muscles are the most obviously
affected, manifesting as drooping eyelids, double vision, difficulty swallowing and general fatigue. There is no
actual paralysis of muscles involved, but a rapid fatiguing of function.

Lupus erythematosus – An autoimmune disease wherein the body produces antibodies against a variety of organs,
especially connective tissues of skin and joints. Mild Lupus may involve a distinctive butterfly-shaped rash over the
nose and cheeks. Mild lupus may also involve myalgia and arthralgia (remember these words?) Severe or systemic
lupus (SLE) involves inflammation of multiple organ systems such as the heart, lungs, or kidneys. By the way, lupus
means “wolf” in Latin. Maybe a reference to the facial rash that might give a patient a wolf-like appearance.

Musculoskeletal System Procedures

Orthopaedist – “To straighten up children.” Orthopaedics is a surgical subspecialty that in the past devoted much of
its time to treating musculoskeletal deformities in children. Now with improved prenatal diagnosis and better
nutrition, orthopaedists still treat children with spine and limb deformities but also adults with complicated bone
fractures, damaged tendons or ligaments, or needing surgery to replace a damaged hip or knee joint.

Rheumatologist – “To study the flux of fluids.” Say, what? Rheuma is an old medical term for a watery discharge.
Among other diseases, rheumatologists treat joint diseases such as the various forms of arthritis including
rheumatoid arthritis. Inflamed joints accumulate “fluid” and swell among other signs and symptoms. This medical
subspecialty also evaluates and treats osteoporosis, tendonitis, gout and lupus among many other chronic
musculoskeletal pain disorders.

Osteopath/osteopathic physician (D.O.) – The name sounds like a specialty limited to bone disease, but actually,
osteopathic physicians are one of two arms of the medical profession that differ in history and philosophy. At one
time there were many kinds of medical schools originating from various philosophies; allopathic, osteopathic,
homeopathic. Osteopathy originated in the 1890s in response to despair at the lack of effectiveness of many forms of
then primitive treatments. Osteopathy developed an emphasis on the influence of the musculoskeletal system and its
interrelationship to other body systems. D.O.s make use of osteopathic manipulation (bones, ligaments, joints) along
with medication, surgery and all other medical treatments used by M.D. physicians. Also, preventive care has
always been a major emphasis of osteopathic care. M.D.s and D.O.s are licensed by all state medical boards. Learn
about the doctor of osteopathic medicine program at Des Moines University.

Podiatrists, traditionally known as “foot doctors,” are surgical subspecialists in diseases and structural problems of
the feet. They not only provide care for corns, calluses, ingrown toenails and heel spurs, but also treat foot and ankle
injuries, deformities and diseases. Many systemic diseases manifest signs and symptoms in appearance of the feet
such as poor wound healing in diabetes. They also can prescribe special shoes and inserts to treat chronic foot pain
 19

and walking problems. Podiatrists may further specialize in sports medicine, geriatrics or diabetic foot care. Learn
about the doctor of podiatric medicine program at Des Moines University.

Physical therapist – This health care professional has at least two years of specialized training beyond a college
degree. PTs are rehabilitation specialists treating a multitude of medical problems including patients recovering from
joint surgery, limb amputation, a stroke, heart attack and suffering with chronic neuromuscular diseases. In addition
to other treatment modalities, they teach patients exercises to strengthen their body, increase mobility and how to
prevent recurrence of injury. Learn about the doctor of physical therapy program at Des Moines University.

Arthroscopy – A fiberoptic instrument is introduced into a joint cavity in order to visualize surfaces of bones
entering into a joint, find tears in internal joint structures and evaluate sources of inflammation.

Bone scan – A radioactive element in very small amounts, not enough to cause any radiation injury to the patient, is
introduced into the blood stream. The specially selected element accumulates in bone and using a much more
sophisticated version of the old Geiger Counter instrument, the distribution of the element is used to diagnose
potential bone tumors among other bone pathologies.

Electromyography – A big, scary word! But, you are experienced by now in taking them apart. I like to start at the
end and work backward: “a recording of muscle electrical activity.” Fine needles are introduced into muscles in
order to make recordings of contractile activity. This procedure is useful in evaluating causes of paralysis,
diagnosing muscular dystrophy and other neuromuscular disorders.

Muscle biopsy – Cutting out a small tissue sample of muscle in order to examine it under a microscope. This
procedure can be useful in diagnosing muscular dystrophy and other neuromuscular disorders.

Musculoskeletal System Medical Record

Following is an abstract of a simulated patient medical record. Identify each italicized word. If the meaning doesn’t
come right away, take apart the word. If you recognize the organ involved, use the context to help you figure out the
full meaning. Terms are not limited to musculoskeletal system. Remember, this is a cumulative exercise! If you
can’t think of the meaning, hover your cursor over the word for a tip.

A 62 year old male comes to his family physician complaining of pain in his right knee. He walks with a limp which
he says is getting worse and is related to an old football injury. During the course of the examination he reveals that
he also suffers from a “nervous bladder” with polyuria, dysuria and nocturia, but denies hematuria. He smokes two
packs a day, breaths are wheezy and he is short of breath, but denies hemoptysis.

Physical exam: right knee was swollen, warm and had limited range of motion which was painful to perform. Mild
exercise increases wheezing and causes dyspnea. Examination of the heart size reveals cardiomegaly.
No hepatomegaly or splenomegaly was found upon abdominal examination.

Current medication: Prevacid for gastroesophageal reflux disease, nitroglycerine for angina pectoris.

Past medical history: GERD diagnosed with esophagogastroduodenoscopy (EGD). Angina pectoris diagnosed with
treadmill test, cardiac scan and cardiac catherization.

Past surgical history: orchidopexy for cryptorchidism at age nine, tonsillectomy, appendectomy.

Family medical history: mother has chronic nephritis; will be starting dialysis.

Recommended treatments: refer to pulmonologist to evaluate possible emphysema. Refer to orthopaedist

for arthroscopic evaluation of knee. Refer to urologist to evaluate for prostatic hypertrophy, possible cystoscopy.
Office phlebotomist drew specimens for lab work.
 20

Get a piece of paper and pencil and write down two column headings: “Signs” and “Symptoms.” Then take the
following items and put them under the proper heading. You remember the difference between a sign and a
symptom, right? You might want to review the context of these items in the case above before deciding.

Item: cardiomegaly, pain in right knee, right knee is swollen, nervous bladder.pr

In plain English

A 62 year old male comes to his family physician complaining of pain in his right knee. He walks with a limp which
he says is getting worse and is related to an old football injury. During the course of the examination he reveals that
he also suffers from a “nervous bladder” with frequent urination, painful/difficult urination and getting up at night to
urinate, but denies blood in the urine. He smokes two packs a day, breaths are wheezy and he is short of breath, but
denies coughing up blood.

Physical exam: right knee was swollen, warm and had limited range of motion which was painful to perform. Mild
exercise increases wheezing and causes difficulty breathing. Examination of the heart size reveals an enlarged heart.
No enlargement of the liver or spleen was found upon abdominal examination.

Current medication: Prevacid for severe heartburn, nitroglycerine for chest pain related to the heart.

Past medical history: GERD diagnosed with visual examination of the esophagus, stomach and duodenum with a
fiberoptic instrument. Angina pectoris diagnosed with treadmill test, injecting a radioactive element into blood
stream to evaluate heart structure and function and threading a hollow tube through arteries to the heart to inject dye
opaque to X-rays to demonstrate coronary arteries.

Past surgical history: surgical fixation of the testis for undescended testicles at age nine, removal of tonsils, removal
of appendix.

Family medical history: mother has chronic inflammation of kidneys; will be starting medical procedure cleansing
waste from blood in kidney failure.

Recommended treatments: refer to specialist in lung diseases to evaluate possible destruction of lung membranes
needed for oxygen exchange. Refer to specialist in musculoskeletal diseases for visualization of joints with a
fiberoptic instrument (evaluation of knee). Refer to specialist in lower urinary tract diseases and diseases of the male
reproductive tract to evaluate for enlargement of the prostate, possible visualization of the interior of the bladder
with a fiberoptic instrument. Office technician or nurse trained to “cut into veins” to draw blood drew specimens for
lab work.

By the way, what the patient complains of or describes are symptoms: knee hurts, frequent urination. What the
doctor observes and/or measures are signs: right knee is swollen, enlarged heart.

9. THE BRAIN

n The brain is one of the largest and most complex organs in the human body. It is made up of more than
100 billion nerves that communicate in trillions of connections called synapses. The brain is made up
of many specialized areas that work together: • The cortex is the outermost layer of brain cells. Thinking
and voluntary movements begin in the cortex. • The brain stem is between the spinal cord and the rest of
the brain. Basic functions like breathing and sleep are controlled here. • The basal ganglia are a cluster of
structures in the center of the brain. The basal ganglia coordinate messages between multiple other brain
areas. • The cerebellum is at the base and the back of the brain. The cerebellum is responsible for
coordination and balance.
n The brain is also divided into several lobes: • The frontal lobes are responsible for problem solving and
judgment and motor function. • The parietal lobes manage sensation, handwriting, and body position. •
 21

The temporal lobes are involved with memory and hearing. • The occipital lobes contain the brain's visual
processing system.
n The brain is surrounded by a layer of tissue called the meninges. The skull (cranium) helps protect the brain
from injury

Brain & Nervous System Health

n Brain Conditions
n Headache: There are many types of headaches; some can be serious but most are not and are generally
treated with analgesics/painkillers.
n Stroke (brain infarction): Blood flow and oxygen are suddenly interrupted to an area of brain tissue, which
then dies. A blood clot, or bleeding in the brain, are the cause of most strokes.
n Brain aneurysm: An artery in the brain develops a weak area that swells, balloon-like. A brain aneurysm
rupture can causes a stroke.
n Subdural hematoma: Bleeding within or under the dura, the lining inside of the skull. A subdural hematoma
may exert pressure on the brain, causing neurological problems.
n Meningitis: Inflammation of the lining around the brain or spinal cord, usually from infection. Stiff neck,
neck pain, headache, fever, and sleepiness are common symptoms.
n Encephalitis: Inflammation of the brain tissue, usually from infection with a virus. Fever, headache, and
confusion are common symptoms.
n Traumatic brain injury: Permanent brain damage from a traumatic head injury. Obvious mental impairment,
or more subtle personality and mood changes can occur.
n Parkinson's disease: Nerves in a central area of the brain degenerate slowly, causing problems with
movement and coordination. A tremor of the hands is a common early sign.

n Epidural hematoma: Bleeding between the tough tissue (dura) lining the inside of the skull and the skull
itself, usually shortly after a head injury. Initial mild symptoms can progress rapidly to unconsciousness
and death, if untreated.
n Intracerebral hemorrhage: Any bleeding inside the brain.
n Concussion: A brain injury that causes a temporary disturbance in brain function. Traumatic head injuries
cause most concussions.
n Cerebral edema: Swelling of the brain tissue in response to injury or electrolyte imbalances.
n Brain tumor: Any abnormal tissue growth inside the brain. Whether malignant (cancer) or benign, brain
tumors usually cause problems by the pressure they exert on the normal brain.
n Glioblastoma: An aggressive, malignant brain tumor (cancer). Brain glioblastomas progress rapidly and are
very difficult to cure.
n Hydrocephalus: An abnormally increased amount of cerebrospinal (brain) fluid inside the skull. Usually
this is because the fluid is not circulating properly
n Normal pressure hydrocephalus: A form of hydrocephalus that often causes problems walking, along with
dementia and urinary incontinence. Pressures inside the brain remain normal, despite the increased fluid.

n Huntington's disease: An inherited nerve disorder that affects the brain. Dementia and difficulty controlling
movements (chorea) are its symptoms.
n Epilepsy: The tendency to have seizures. Head injuries and strokes may cause epilepsy, but usually no
cause is identified.
n Dementia: A decline in cognitive function resulting from death or malfunction of nerve cells in the brain.
Conditions in which nerves in the brain degenerate, as well as alcohol abuse and strokes, can cause
dementia.
n Alzheimer’s disease: For unclear reasons, nerves in certain brain areas degenerate, causing progressive
dementia. Alzheimer’s disease is the most common form of dementia.
n Brain abscess: A pocket of infection in the brain, usually by bacteria. Antibiotics and surgical drainage of
the area are often necessary.
n Concussion (Traumatic Brain Injury)
n a concussion is most often caused by a sudden direct blow or bump to the head.
 22

n The most common and least serious type of traumatic brain injury is called a concussion. The word comes
from the Latin concutere, which means "to shake violently. According to the CDC, between 2001 and
2009, an estimated 173,285 people under age 19 were treated in hospital emergency rooms for concussions
related to sports and recreation activities. Other causes include car and bicycle accidents, work-related
injuries, falls, and fighting.
n The brain is made of soft tissue. It's cushioned by spinal fluid and encased in the protective shell of the
skull. When you sustain a concussion, the impact can jolt your brain. Sometimes, it literally causes it to
move around in your head. Traumatic brain injuries can cause bruising, damage to the blood vessels, and
injury to the nerves.
n The result? Your brain doesn't function normally. If you've suffered a concussion, vision may be disturbed,
you may lose equilibrium, or you may fall unconscious. In short, the brain is confused. That's why people
see stars when they get brain shocks.

n What Is Hypertension?
n Hypertension, or high blood pressure, is a common condition that will catch up with most people who live
into older age. Blood pressure is the force of blood pressing against the walls of the arteries. When it's too
high, it raises the heart's workload and can cause serious damage to the arteries. Over time, uncontrolled
high blood pressure increases the risk of heart disease, stroke, and kidney
n Hypertension and Stress
n Stress can make one's blood pressure spike, but there's no evidence that it causes high blood pressure as an
ongoing condition. However, stress may affect risk factors for heart disease, so it may have an indirect
connection to hypertension. Stress may lead to other unhealthy habits, such as a poor diet, alcohol use, or
smoking, which can contribute to high blood pressure and heart disease.
n Hypertension and Weight
n Being overweight places a strain on the heart and increases your risk of high blood pressure. That is why
diets to lower blood pressure are often also designed to control calories. They typically call for cutting fatty
foods and added sugars, while increasing fruits, vegetables, lean protein, and fiber. Even losing 10 pounds
can make a difference.
n Hypertension and Alcohol
n Drinking too much alcohol can increase your blood pressure. Guidelines from the American Heart
Association state that if you drink alcohol, you should limit the amount to no more than two drinks a day
for men, or one a day for women. They define a drink as one 12-ounce beer, four ounces of wine, 1.5
ounces of 80-proof spirits, or one ounce of 100-proof spirits.
n Hypertension and Caffeine
n If caffeine can make you jittery, can it also raise your blood pressure? It might have a temporary effect, but
studies haven't shown any link between caffeine and the development of hypertension. You can safely
drink one or two cups a day, according to the American Heart Association.
n Hypertension and Pregnancy
n Gestational hypertension is a kind of high blood pressure that occurs in the second half of pregnancy.
Without treatment, it may lead to a serious condition called preeclampsia that endangers both the mother
and baby. The condition can limit blood and oxygen flow to the baby and can affect the mother's kidneys
and brain. After the baby is born, the mother’s blood pressure usually returns to its normal level.
n Hypertension and Medicine
n Cold and flu medicines that contain decongestants are one of several classes of medication that can cause
blood pressure to rise. Others include NSAID pain relievers, steroids, diet pills, birth control pills, and
some antidepressants. If you have high blood pressure, talk to you doctor about what drugs and
supplements you are taking that may affect blood pressure.

Brain Treatments
n Thrombolytics: Clot-busting medicines injected into the veins can improve or cure some strokes if given
within a few hours after symptoms start.
n Antiplatelet agents: Medicines like aspirin and clopidogrel (Plavix) help prevent blood clots. This can
reduce the chance of a stroke.
 23

n Cholinesterase inhibitors: These medicines can improve brain function slightly in mild or moderate
Alzheimer’s disease. They do not slow or prevent Alzheimer’s disease.
n Antibiotics: When a brain infection is caused by bacteria, antibiotics can kill the organisms and make a
cure more likely.
n Levodopa: A medicine that increases brain levels of dopamine, which is helpful in controlling symptoms of
Parkinson’s disease.

n Brain surgery: An operation on the brain can cure some brain tumors. Brain surgery may be performed any
time increased pressure in the brain threatens brain tissue.
n Ventriculostomy: A drain is placed into the natural spaces inside the brain (ventricles). Ventriculostomy is
usually performed to relieve high brain pressures.
n Craniotomy: A surgeon drills a hole into the side of the skull to relieve high pressures.
n Lumbar drain: A drain is placed into the fluid around the spinal cord. This can relieve pressure on the brain
and spinal cord.
n Radiation therapy: If cancer affects the brain, radiation can reduce symptoms and slow the cancer's growth.

Treatment: The DASH Diet

n You may be able to lower your blood pressure by switching to a better diet. The DASH Diet -- Dietary
Approaches to Stop Hypertension -- involves eating more fruits, vegetables, whole-grain foods, low-fat
dairy, fish, poultry, and nuts. You should eat less red meat, saturated fats, and sweets. Reducing sodium in
the diet can also have a significant effect.
n Treatment: Exercise
n Regular exercise helps lower blood pressure. Adults should get about 150 minutes of moderate-intensity
exercise every week. That could include gardening, walking briskly, bicycling, or other aerobic exercise.
Muscle-strengthening activities are recommended at least two days a week and should work all major
muscle groups.

n Treatment: Diuretics
n Diuretics are often the first choice if diet and exercise changes aren't enough. Also called "water pills," they
help the body shed excess sodium and water to lower blood pressure. That means you'll urinate more often.
Some diuretics may deplete the body's potassium, causing muscle weakness, leg cramps, and fatigue. Some
can increase blood sugar levels in diabetics. Erectile dysfunction is a less common side effect.
n Treatment: Beta-blockers
n Beta-blockers work by slowing the heart rate, which means that the heart doesn't have to work as hard.
They are also used to treat other heart conditions, such as an abnormal heart rate called arrhythmia. They
may be prescribed along with other medications. Side effects can include insomnia, dizziness, fatigue, cold
hands and feet, and erectile dysfunction.
n Treatment: ACE Inhibitors
n ACE inhibitors reduce the body's supply of angiotensin II -- a substance that makes blood vessels contract
and narrow. The result is more relaxed, open (dilated) arteries, as well as lower blood pressure and less
effort for the heart. Side effects can include a dry cough, skin rash, or dizziness, and high levels of
potassium. Women should not become pregnant while taking an ACE inhibitor.
n Treatment: ARBs
n Instead of reducing the body's supply of angiotensin II, these drugs block receptors for angiotensin -- as if
placing a shield over a lock. This blockade prevents the chemical's artery-tightening effects, and lowers
your blood pressure. ARBs can take several weeks to become fully effective. Possible side effects include
dizziness, muscle cramps, insomnia, and high levels of potassium. Women should not become pregnant
while taking this medication.
n Treatment: Calcium Channel Blockers
n Calcium channel blockers slow the movement of calcium into the cells of the heart and blood vessels. Since
calcium causes stronger heart contractions, these drugs ease the heart's contraction and relax the blood
vessels. They can cause dizziness, heart palpitations, swelling of the ankles, and constipation. Take them
with food or milk and avoid grapefruit juice and alcohol because of possible interactions.
 24

n Treatment: Other Medications

n Other medications that relax the blood vessels include vasodilators, alpha blockers, and central agonists.
Side effects can include dizziness, a fast heart beat or heart palpitations, headaches, or diarrhea. Your
doctor may suggest them if other blood pressure medications are not working well enough or if you have
another condition.
n Treatment: Complementary Therapies
n Meditation can put the body into a state of deep rest, which can lower blood pressure. Yoga, tai chi, and
deep breathing also help. These relaxation techniques should be combined with other lifestyle changes,
such as diet and exercise. Be aware that herbal therapies may conflict with other drugs you take, and some
herbs actually raise blood pressure. Tell your doctor if you take herbal or other dietary supplements.
n Living With High Blood Pressure
n Hypertension is often a life-long condition. It's important to take your medications and continue to monitor
your blood pressure. If you keep it under control, you can reduce the risk of stroke, heart disease, and
kidney failure.

MAJOR CHEMICAL ELEMENTS OF THE HUMAN BODY

n Almost 99% of the mass of the human body is made up of six elements: oxygen, carbon, hydrogen,
nitrogen, calcium, and phosphorus.
n Only about 0.85% is composed of another five elements: potassium, sulfur, sodium, chlorine, and
magnesium. All are necessary to life.
n The remaining elements are trace elements, of which more than a dozen are thought to be necessary
for life, or play a role in good health (e.g., fluorine, which hardens dental enamel but seems to have
no other function).
n Because water constitutes almost 70% of the human body, Oxygen and Hydrogen are the most
abundant elements in the human body (almost 75%)
n The elemental composition of the human body can be looked at from the point of view of either mass
composition, or atomic composition.
n To illustrate both views, the adult male human body is approximately 57% water, and water is 11%
hydrogen by mass but 67% by count of atoms (i.e. 67 atomic percent).
n Thus, most of the mass of the human body is oxygen, but most of the atoms in the human body are
hydrogen atoms.
n Body composition may also be analyzed in terms of molecular type (e.g., water, protein, connective tissue,
fats (or lipids) apatite (in bones), carbohydrates (such as glycogen and glucose) and DNA. In terms of
tissue type, the body may be analyzed into water, fat, muscle, bone, etc. In terms of cell type, the body
contains hundreds of different types of cells, but notably, the largest number of cells contained in a human
body (though not the largest mass of cells) are not human cells, but consist of bacteria (bacterial cells)
residing in the normal human gastrointestinal tract.

n Oxygen (O) a component of water and other compounds; oxygen gas is essential for respiration
n Hydrogen (H) a component of water and most other compounds in the body.
n Carbon (C) found in all organic molecules. It is what makes the crucial difference between organic and
inorganic matter
n Nitrogen (N) found in proteins, nucleic acids, and other organic compounds; 78% of the air we breathe
is nitrogen but only 21% oxygen.

n Phosphorus (P) found in the nucleus of every cell in the body (including white blood cells), nucleic
acids, high-energy compounds, and phosphate buffer system; a major component of outer bone; combines
 25

with such elements as iron, potassium, sodium, magnesium and calcium; necessary for the reproductive
system and sexual function; necessary for muscle tissue and growth; an essential nutrient for the nerves.
n Sulphur (S) found in many amino acids as well as thiamine and biotin; necessary for developmental and
neurological processes and for synthesis of collagen; detoxifies; increases blood circulation; reduces
muscle cramping and back pain; removes inflammation; assists in the healing of muscles; helps the liver
produce choline; an important element in nerves and the myelin sheath; stimulates flow of bile; regulates
heart and brain function; promotes healthy skin, nails, and hair; helps lubricate joints.

n Pottasium (K) – important for proper membrane function, nerve impulses, and muscle contractions; major
cation in cytoplasm; a primary electrolyte and alkalizer; attracts oxygen to tissues; helps eliminate toxins
from the body.
n Selenium (Se) a powerful antioxidant; vital to the immune system; major part of apoptosis (normal cell
death in the body); helps maintain cell integrity; supports heart function; helps slow the aging process;
delays oxidation of polyunsaturated fatty acids.
n Sodium (Na) – stored in stomach walls, joints, and gallbladder; helps prevent blood clotting; important for
membrane function, nerve impulses, and muscle contractions; major cation in body fluids; contributes to
the alkalinity of the lymph and blood; works with the bicarbonate buffer system in the digestive tract to
prevent hydrochloric acid from burning stomach walls; helps retain calcium and cholesterol liquid in the
body; helps with excretion of carbon dioxide (CO2).
n
n Germanium (Ge) helps activate various organs to attract more oxygen; expels harmful pollutants and
pathogens from the body; helps maintain a strong immune system by assisting in the production of killer
cells and T-suppresser cells; assists in electron transmissions.
n Iodine (I) a major component of thyroid hormones (thyroxine and T3); necessary for the metabolism of
fats and such minerals as calcium, silica, and phosphorus; essential for spleen, liver, and brain function;
neutralizes albumin.
n Iron (Fe) essential for oxygen transport and energy capture; component of hemoglobin, myoglobin, and
cytochromes in cell respiration.
n Magnesium (Mg) required for activation of several enzymes; vital for strong bones and teeth; essential
for brain and liver function; calms nerves; promotes cell growth; increases tissue elasticity; necessary for
metabolism of ATP-ADP.
n Manganese (Mn) cofactor for some enzymes; because it is found with lecithin, it is involved in the
synthesis of fatty acids and cholesterol; strengthens nerves and thought processes; element in body linings
and connective tissues; helps with eyesight; enhances body s recuperative abilities and resistance to disease.
n Boron (B) assists and improves retention of calcium, magnesium, and phosphorus; necessary for brain
function, memory and alertness as well as for the activation of vitamin D.
n Calcium (Ca) found mainly in bones and teeth important for membrane function, nerve impulses,
muscle contractions, and blood clotting.
n Chlorine (Cl) important for membrane function and water absorption; chloride is the major anion in
body fluids and part of hydrochloric acid (HCl) in gastric juices.
n Chromium (Cr) master regulator of insulin; potent metabolic hormone in the metabolism of proteins,
carbohydrates, and fats; assists neurotransmitters; helps with the function of the brain, thyroid, and
hormonal balance.
n Cobalt (Co) a vital part of vitamin B12; stimulates numerous enzymes; helps build red blood cells and
with iron absorption.
 26

n Copper (Cu) involved in the synthesis of hemoglobin, melanin, and elastin; an enzyme cofactor; part of
some cytochromes in cell respiration; assists in phospholipid synthesis, protein metabolism, vitamin C
oxidation, and the formation of RNA.

NUTRIENTS AND HEALTH

There are eight key nutrients that are necessary to remain healthy. These include protein, water, vitamin D, vitamin
C, iron, the B vitamins, fat, as well as carbohydrates.

THE SIX MAJOR NUTRIENTS AND THEIR PRIMARY FUNCTIONS

WATER: Dissolves and carries nutrients, removes waste, and regulates body temperature
PROTEIN: builds new tissues, antibodies, enzimes, hormones, and other compounds
MINERALS: help build bones and teeth; aid in muscle function and nervous system activity
CARBOHYDRATE: provides energy
FAT: provides long-term energy insulation, and protection
VITAMINS: facilitate use of other nutrients; involved in regulating growth and manufacturing hormones

PROTEINS
n Everything in life needs protein to live,
n Protein is a macro nutrient necessary for the proper growth and function of the human body. There is
considerable debate over the amount of protein a person needs to consume per day, the current
recommended daily intake (RDI) for protein is 46 grams for women aged 19-70, and 56 grams for men
aged 19-70. Any excess protein is turned into energy by the body, and it is controversial whether this
excess protein causes a strain on the liver.
n A deficiency in protein leads to muscle atrophy, and impaired functioning of the human body in general.
n High protein foods include meat, fish, cheese, beans, lentils, yogurt, eggs, nuts, and seeds. vegetables can
be a great source of protein.
n

A WORD ON IRON AND CALCIUM

n Iron (Fe) is the most abundant element on the planet earth. It can be found in outer and inner core. This
element is playing very crucial role the human’s health.
n Our body requires around 100 miligrams per day of Fe.
n Males of average height have about 4 grams of iron in their body, females about 3.5 grams; children will
usually have 3 grams or less. These 3-4 grams are distributed throughout the body in hemoglobin, tissues,
muscles, bone marrow, blood proteins, enzymes, ferritin, hemosiderin, and transport in plasma.
n Iron regulates DNA synthesis, growth, healing, immune function, reproduction and even metabolism.
n Without iron our red blood cells would not be able to carry oxygen. Hemoglobin and Myoglobin are the
two proteins in red blood cells that are responsible for delivering oxygen via blood and muscles.
n When you climb a hill, run or ride a bike you get a better athletic performance if more oxygen is delivered
to your muscles.
n SOURCES:
n Best sources of Iron is eggs, dried beans, dried fruits, apples, whole grains, red meat, fish such as tuna and
salmon.
n Iron from Meat and eggs is better absorbed than that from plants.
 27

n Approximately 50% of pregnant women, 20% of women, and 3% of men have Fe deficiency
n People who have iron deficiency suffer irritability, general weakness, hair loss, grooved nails, brittle nails,
or pale skin
n Understanding iron metabolism is also important for understanding diseases of iron overload, such as
hereditary hemochromatosis, and iron deficiency, such as iron deficiency anemia.
n Calcium (1.5%) is the most common mineral in the human body — nearly all of it found in bones and
teeth. Ironically, calcium's most important role is in bodily functions, such as muscle contraction and
protein regulation.
n Calcium is the most plentiful mineral found in the human body. The teeth and bones contain the most
calcium. Nerve cells, body tissues, blood, and other body fluids contain the rest of the calcium.
Function
n Calcium is one of the most important minerals for the human body. Calcium helps form and maintain
healthy teeth and bones. Proper levels of calcium over a lifetime can help prevent osteoporosis.
n Calcium helps your body with:
n Building strong bones and teeth
n Clotting blood
n Sending and receiving nerve signals
n Squeezing and relaxing muscles
n Releasing hormones and other chemicals
n Keeping a normal heartbeat

n Food Sources
n CALCIUM AND DAIRY PRODUCTS
n Many foods contain calcium, but dairy products are the best source. Milk and dairy products such as
yogurt, cheeses, and buttermilk contain a form of calcium that your body can absorb easily.
n Whole milk (4% fat) is recommended for children ages 1 to 2. Adults and children over the age of 2 should
drink low-fat (2% or 1%) or skim milk and other dairy products. Removing the fat will not lower the
amount of calcium in a dairy product.
n Yogurt, most cheeses, and buttermilk are excellent sources of calcium and come in low-fat or fat-free
versions.
n Milk is also a good source of phosphorus and magnesium, which help the body absorb and use calcium.
n Vitamin D is needed to help the body use calcium. Milk is fortified with vitamin D for this reason.
OTHER SOURCES OF CALCIUM
n Green leafy vegetables such as broccoli, collards, kale, mustard greens, turnip greens, and bok choy or
Chinese cabbage are good sources of calcium.
n Other sources of calcium that can help meet your body's calcium needs:
n Salmon and sardines canned with their soft bones
n Almonds, Brazil nuts, sunflower seeds, tahini, and dried beans
n Blackstrap molasses
n Calcium is added to several food products, such as orange juice, soy milk, tofu, ready-to-eat cereals, and
breads. These are a very good source of calcium for persons who do not eat a lot of dairy products or who
are on a vegan diet.
n Ways to make sure you receive or absorb the calcium in your diet:
n Cook foods in a small amount of water for the shortest possible time to keep more calcium in the foods you
eat.
n Be careful about what you eat with calcium-rich foods. Certain fibers, such as wheat bran and foods with
oxalic acid (spinach and rhubarb) can bind with calcium and prevent it from being absorbed.

Calcium
Calcium is required for the construction of bone; it forms part of the substance cementing together the walls of
adjacent cells; and it is vital in the responsiveness to stimuli of muscle and nerve cells, which determines their
excitability. The main sources of calcium are milk and milk products; meat, in which it is bound to proteins; and
vegetables, in which it is bound to phytates (phytic acid) and oxalates (the salt of oxalic acid).
 28

The absorption of calcium is influenced by conditions within the lumen of the small intestine. The acid secretion
from the stomach converts the calcium to a salt, which is absorbed primarily in the duodenum. Unabsorbed calcium
is precipitated in the ileum and is excreted in the feces. Lactose, the sugar of milk, aids calcium absorption, whereas
excess fatty acid and high concentrations of magnesium and oxalates interfere with it.

Calcium is absorbed across the brush border of the enterocyte cell membrane by a mechanism that requires energy.
Vitamin D is essential to this process, and, when it is deficient, the active transport of calcium stops. Parathyroid
hormone (parathormone) and growth hormone from the pituitary gland also influence calcium absorption. An
average diet contains 1,200 mg of calcium, one-third of which is absorbed. In the passage of the blood through the
kidney, 99 percent of the circulating calcium is reabsorbed. Thus, in kidney failure as well as in malabsorption
states, excessive losses of calcium occur. In calcium deficiency, calcium is resorbed from the bone, which thereby
weakens and softens the skeletal structure.

Magnesium

Magnesium is the ninth most abundant element in the universe, but it is the eleventh most abundant
element by mass in the human body. Magnesium is a mineral that is present in relatively large amounts in
the body. Researchers estimate that the average person’s body contains about 25 grams of magnesium,
and about half of that is in the bones. Magnesium is important in more than 300 chemical reactions that
keep the body working properly.

Its ions are essential to all cells. They interact with polyphosphate compounds such as ATP, DNA, and
RNA. Hundreds of enzymes require magnesium ions to function. Magnesium compounds are used
medicinally as common laxatives, antacids (e.g., milk of magnesia), and to stabilize abnormal nerve
excitation or blood vessel spasm such as in eclampsia.

People get magnesium from their diet, but sometimes magnesium supplements are needed if
magnesium levels are too low. Dietary intake of magnesium may be low, particularly among
women. An easy way to remember foods that are good magnesium sources is to think fiber. Foods
that are high in fiber are generally high in magnesium. Dietary sources of magnesium include legumes,
whole grains, vegetables (especially broccoli, squash, and green leafy vegetables), seeds, and nuts
(especially almonds). Other sources include dairy products, meats, chocolate, and coffee. Water with a
high mineral content, or “hard” water, is also a source of magnesium. People take magnesium to
prevent or treat magnesium deficiency. Magnesium deficiency is not uncommon in the US. It’s particularly
common among African Americans and the elderly. Magnesium is also used as a laxative for
constipation and for preparation of the bowel for surgical or diagnostic procedures. It is also used as an
antacid for acid indigestion. Some people use magnesium for diseases of the heart and blood vessels
including chest pain, irregular heartbeat, high blood pressure, high levels of “bad” cholesterol called low-
density lipoprotein (LDL) cholesterol, low levels of “good” cholesterol called high-density lipoprotein (HDL)
cholesterol, heart valve disease (mitral valve prolapse), and heart attack. Magnesium is also used for
treating attention deficit-hyperactivity disorder (ADHD), anxiety, chronic fatigue syndrome (CFS), Lyme
disease, fibromyalgia, leg cramps during pregnancy, diabetes, kidney stones, migraine headaches, weak
bones (osteoporosis), premenstrual syndrome (PMS), altitude sickness, urinary incontinence, restless leg
syndrome, asthma, hayfever, multiple sclerosis, and for preventing hearing loss. Athletes sometimes
use magnesium to increase energy and endurance. Some people put magnesium on their skin to
treat infected skin ulcers, boils, and carbuncles; and to speed up wound healing. Magnesium is also used
as a cold compress in the treatment of a severe skin infection caused by strep bacteria (erysipelas) and
as a hot compress for deep-seated skin infections. Some companies that manufacturer
magnesium/calcium combination supplements promote a 2:1 or 3:1 ratio as being ideal for absorption of
these elements. However, there is no credible research to support this claim. Claims that coral calcium
products have ideal combinations of magnesium and calcium to cure a variety of diseases and conditions
are being carefully evaluated by the US Food and Drug Administration (FDA) and US Federal Trade
 29

Commission (FTC).
How does it work?
Magnesium is required for the proper growth and maintenance of bones. Magnesium is also required for
the proper function of nerves, muscles, and many other parts of the body. In the stomach, magnesium
helps neutralize stomach acid and moves stools through the intestine.

There's some evidence that eating foods high in magnesium and other minerals can help prevent high
blood pressure in people with prehypertension.

Intravenous or injected magnesium is used to treat other conditions, such as eclampsia during pregnancy
and severe asthma attacks. Magnesium is also the main ingredient in many antacids and laxatives.

Severe magnesium deficiencies are rare. They're more likely in people who:

Have kidney disease

Have Crohn's disease or other conditions that affect digestion
Have parathyroid problems
Take antibiotics or drugs for diabetes and cancer
Are older adults
Abuse alcohol
Health care providers sometimes suggest that people with these conditions take magnesium
supplements.

Proton pump inhibitors (PPIs) a common type of medicine used to treat acid reflux, have also been tied to
low magnesium levels. Examples of PPIs include dexlansoprazole ( Dexilant), esomeprazole ( Nexium),
lansoprazole ( Prevacid), omeprazole ( Prilosec, Zegerid), pantoprazole ( Protonix), and rabeprazole (
Aciphex). If you take any of these medicines on a long-term basis, your health care provider may check
your magnesium level with a blood test.

Magnesium is a chemical element with symbol Mg and atomic number 12. It is a shiny gray solid which
bears a close physical resemblance to the other five elements in the second column (Group 2, or alkaline
earth metals) of the periodic table: they each have the same electron configuration in their outer electron
shell producing a similar crystal structure.
It is synthesized in large, aging stars from the sequential addition of three helium nuclei to a carbon
nucleus. When such a star explodes as a supernova, much of its magnesium is expelled into the
interstellar medium, where it can be recycled into new star systems. Consequently, magnesium is the
eighth most abundant element in the Earth's crust[6] and the fourth most common element in the Earth
(below iron, oxygen and silicon), making up 13% of the planet's mass and a large fraction of the planet's
mantle. It is the third most abundant element dissolved in seawater, after sodium and chlorine.[7]
In commerce, the chief use for the metal is as an alloying agent to make aluminium-magnesium alloys,
sometimes called magnalium or magnelium. Since magnesium is less dense than aluminium, this alloy is
prized for its properties of lightness combined with strength.

An average diet contains around 300 mg of magnesium, of which two-thirds is absorbed. Half of the absorbed
magnesium is excreted by the kidneys, which can regulate the amount within a range of 1 to 150 millimoles per day.
This control is subject to the influences of the parathyroid hormone parathormone and the thyroid hormone
calcitotonin. Magnesium is important to neuromuscular transmission. It is also an important cofactor in the enzymic
processes that form the matrix of bone and in the synthesis of nucleic acid. Magnesium deficiency can result from
the overuse of diuretics and from chronic renal failure, chronic alcoholism, uncontrolled diabetes mellitus, and
intestinal malabsorption.
 30

Magnesium has an inverse relationship with calcium. Thus, if food is deficient in magnesium, more of the calcium
in the food is absorbed. If the blood level of magnesium is low, calcium is mobilized from bone. The treatment of
hypocalcemia due to malabsorption includes administration of magnesium supplements.

Hematinics
Hematinics are substances that are essential to the proper formation of the components of blood. Examples of
hematinics include folic acid, vitamin B12, and iron. In addition, vitamin D, which helps maintain the health of
bones—the reservoirs of new blood cells—may also have a role in protecting hemoglobin and in stimulating the
formation of new blood cells.

Folic acid
Folic acid (pteroylglutamic acid) is necessary for the synthesis of nucleic acids and for cell replication. Folic acid
deficiency results in an impaired maturation of red blood cells (erythrocytes). Folates are synthesized by bacteria
and plants and are hydrolyzed to folic acid in the intestine. Milk and fruit are the main sources of folic acid,
providing on average 500 micrograms daily. Folic acid is stored in the liver.

The hydrolysis of the folates, a necessary step to absorption, takes place on the brush borders of jejunal enterocytes
and is completed on lysosomes (structures within the cell that contain various hydrolytic enzymes and are part of the
intracellular digestive system). When hydrolysis of folates is disturbed, anemia develops. This process is interfered
with by certain drugs, especially phenytoin, used in the management of epilepsy, and by the long-term use of
sulfonamides in the suppression of disease. A methyl group is added to pteroylglutamic acid in the enterohepatic
circulation in the liver and is excreted in the bile. Approximately 100 micrograms are utilized each day. The method
of absorption is uncertain.

Vitamin B12
Vitamin B12, also called cobalamin because it contains cobalt, is essential to the formation of blood cells. It is a
coenzyme that assists the enzymes responsible for moving folate into the cell interior. Vitamin B12 is a product of
bacterial metabolism. Although bacteria in the colon also produce vitamin B12, it cannot be absorbed at that site.
Vitamin B12 occurs in a bound form in food and is liberated by proteolytic activity in the stomach and small
intestine. It then binds with intrinsic factor (IF), a glycoprotein produced by the same parietal cells that form
hydrochloric acid. Intrinsic factor is essential to transport, and the B12 protein complex, known as transcobalamin II,
is necessary to transfer the vitamin from the intestine to the rest of the body. Once the IF is attached, further
proteolytic digestion of the bound vitamin is prevented. Absorption is confined to the distal 100 cm of ileum,
especially the last 20 cm, where the complex binds to receptors in the brush border of the enterocytes. The process is
slow; it takes three hours from its presentation in food to its appearance in the peripheral blood via the enterohepatic
circulation and hepatic veins. The daily requirement of vitamin B12 is one microgram. Vitamin B12 is stored
primarily in the liver.

Iron

Iron is necessary for the synthesis of hemoglobin, the oxygen-carrying compound of the red blood cells. It also has
an important role as a cofactor in intracellular metabolism. The main dietary sources are meat, eggs, nuts, and seeds.
The average daily diet contains approximately 20 mg of iron; humans are unable to excrete iron that has been
absorbed in excess of the daily requirement of 1 mg.

The acid in the stomach prevents the formation of insoluble complexes, as does vitamin C. Some amino acids from
dietary protein stabilize the iron in low molecular weight complexes. Phosphates and phytates of vegetable origin,
some food additives, and the inhibition of acid secretion impede the absorption of iron. Iron is almost wholly
absorbed in the duodenum by a process that involves metabolic activity requiring energy. Most of the iron remains
trapped in the surface enterocytes and is lost when the cells die and are shed into the intestine. The amount of iron
 31

lost seems to be related in some way to the state of the body’s iron stores, although this can be overcome if very
large doses of iron are taken orally. Alcohol in the stomach and duodenum increases the rate of absorption.
Transport of the iron from the enterocyte is achieved by binding to a carrier, a plasma protein called transferrin.
From the intestine it passes into the portal circulation and the liver. When the loss of iron is increased, as in
excessive menstruation and in bleeding disorders, the rate of absorption is stepped up from less than 1 mg per day to
1.5 mg or more.

Vitamin D
Vitamin D is essentially a hormone and is available from two sources. First, under the influence of photosynthesis
made possible by ultraviolet rays from the Sun, a sterol compound from the liver (dehydrocholesterol) is converted
to vitamin D3. This supplies enough vitamin D3 for human needs. In the absence of exposure to sunlight, dietary
supplements become necessary. Eggs, liver, fortified bread, and milk are the main sources of vitamin D. Deficiency
of vitamin D occurs when there is lack of sunlight and inadequate vitamin D in the diet. It may also result from
disease or after resection of the small intestine, which may cause malabsorption. In these circumstances softening of
bone (osteomalacia) and rickets may occur.

In the jejunum vitamin D is incorporated along with bile salts and fatty acids into the micelles, and, subsequently, as
the provitamin D1, vitamin D is absorbed in the ileum and then passes into the circulation via the portal vein. A
specific bloodborne protein, an alpha-1–globulin, carries it to the liver, where the process of chemical change to the
active hormone begins by hydroxylation to cholecalciferol. The derivatives are conveyed from the liver to various
tissues, including the skin, bone, and parathyroid glands. In the intestine vitamin D influences the permeability of
the brush borders of the enterocytes to calcium.
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Vitamin D levels can influence hemoglobin production in the body. For example, persons with low levels of vitamin
D may develop anemia, and hemoglobin levels in these individuals can be increased by vitamin D supplements.
Although the mechanism by which vitamin D influences hemoglobin production is unclear, research has suggested
that it may protect the oxygen-carrying molecule via a protective anti-inflammatory action. Vitamin D has also been
shown to augment the production of red blood cells in the presence of erythropoietin, a hormone produced primarily
in the kidneys that influences the rate of red cell production.

VITAMINS AND THEIR FUNCTION IN THE BODY

Vitamin, any of several organic substances that are necessary in small quantities for normal health and growth in
higher forms of animal life. Vitamins are distinct in several ways from other biologically important compounds such
as proteins, carbohydrates, and lipids. Although these latter substances also are indispensable for proper bodily
functions, almost all of them can be synthesized by animals in adequate quantities. Vitamins, on the other hand,
generally cannot be synthesized in amounts sufficient to meet bodily needs and therefore must be obtained from the
diet or from some synthetic source. For this reason, vitamins are called essential nutrients. Vitamins also differ from
the other biological compounds in that relatively small quantities are needed to complete their functions. In general
these functions are of a catalytic or regulatory nature, facilitating or controlling vital chemical reactions in the
body’s cells. If a vitamin is absent from the diet or is not properly absorbed by the body, a specific deficiency
disease may develop.

Vitamins are usually designated by selected letters of the alphabet, as in vitamin D or vitamin C, though they are
also designated by chemical names, such as niacin and folic acid. Biochemists traditionally separate them into two
groups, the water-soluble vitamins and the fat-soluble vitamins.
The vitamins
vitamin alternative names/forms biological function symptoms of deficiency
Water-soluble
 32

component of a coenzyme in
impairment of the nerves and
thiamin vitamin B1 carbohydrate metabolism; supports
heart muscle wasting
normal nerve function
component of coenzymes required
inflammation of the skin,
for energy production and lipid,
riboflavin vitamin B2 tongue, and lips; ocular
vitamin, mineral, and drug
disturbances; nervous symptoms
metabolism; antioxidant
component of coenzymes used
broadly in cellular metabolism, skin lesions, gastrointestinal
niacin nicotinic acid, nicotinamide
oxidation of fuel molecules, and fatty disturbances, nervous symptoms
acid and steroid synthesis
component of coenzymes in
metabolism of amino acids and other
pyridoxine, pyridoxal, nitrogen-containing compounds; dermatitis, mental depression,
vitamin B6
pyridoxamine synthesis of hemoglobin, confusion, convulsions, anemia
neurotransmitters; regulation of
blood glucose levels
impaired formation of red blood
component of coenzymes in DNA
cells, weakness, irritability,
folate, folacin, synthesis, metabolism of amino
folic acid headache, palpitations,
pteroylglutamic acid acids; required for cell division,
inflammation of mouth, neural
maturation of red blood cells
tube defects in fetus
cofactor for enzymes in metabolism
of amino acids (including folic acid) smoothness of the tongue,
vitamin B12 cobalamin, cyanocobalamin and fatty acids; required for new cell gastrointestinal disturbances,
synthesis, normal blood formation, nervous symptoms
and neurological function
weakness, gastrointestinal
as component of coenzyme A,
disturbances, nervous
pantothenic essential for metabolism of
symptoms, fatigue, sleep
acid carbohydrate, protein, and fat;
disturbances, restlessness,
cofactor for elongation of fatty acids
nausea
dermatitis, hair loss,
cofactor in carbohydrate, fatty acid,
biotin conjunctivitis, neurological
and amino acid metabolism
symptoms
swollen and bleeding gums,
antioxidant; synthesis of collagen,
soreness and stiffness of the
carnitine, amino acids, and
joints and lower extremities,
vitamin C ascorbic acid hormones; immune function;
bleeding under the skin and in
enhances absorption of non-heme
deep tissues, slow wound
iron (from plant foods)
healing, anemia
Fat-soluble
normal vision, integrity of epithelial
ocular disturbances leading to
cells (mucous membranes and skin),
retinol, retinal, retinoic acid, blindness, growth retardation,
vitamin A reproduction, embryonic
beta-carotene (plant version) dry skin, diarrhea, vulnerability
development, growth, immune
to infection
response
calciferol, calatriol (1,25-
dihydroxy vitamin D1 or
maintenance of blood calcium and
vitamin D hormone), defective bone growth in
vitamin D phosphorus levels, proper
cholecalciferol (D3; plant children, soft bones in adults
mineralization of bones
version), ergocalciferol (D2;
animal version)
 33

antioxidant; interruption of free

alpha-tocopherol, tocopherol,
vitamin E
tocotrienol
phylloquinone, menaquinone,
vitamin K
menadione, naphthoquinone
radical chain reactions; protection of peripheral neuropathy,
polyunsaturated fatty acids, cell breakdown of red blood cells
membranes
synthesis of proteins involved in
impaired clotting of the blood
blood coagulation and bone
and internal bleeding
metabolism

Biological significance of vitamins

Vitamins are organic compounds that are necessary for body metabolism and, generally, must be provided from the
diet. For centuries many diseases of dietary deficiency had been recognized, although not well defined. Most of the
vitamin deficiency disorders were biochemically and physiologically defined in the late 19th and early 20th
centuries. The discovery of thiamin (vitamin B1)...
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Discovery and original designation

Some of the first evidence for the existence of vitamins emerged in the late 19th century with the work of Dutch
physician and pathologist Christiaan Eijkman. In 1890 a nerve disease (polyneuritis) broke out among his laboratory
chickens. He noticed that the disease was similar to the polyneuritis associated with the nutritional disorder beriberi.
In 1897 he demonstrated that polyneuritis was caused by feeding the chickens a diet of polished white rice but that it
disappeared when the animals were fed unpolished rice. In 1906–07 British biochemist Sir Frederick Gowland
Hopkins observed that animals cannot synthesize certain amino acids and concluded that macronutrients and salts
could not by themselves support growth.

In 1912—the same year that Hopkins published his findings about the missing nutrients, which he described as
“accessory” factors or substances—a Polish scientist, Casimir Funk, demonstrated that polyneuritis produced in
pigeons fed on polished rice could be cured by supplementing the birds’ diet with a concentrate made from rice
bran, a component of the outer husk that was removed from rice during polishing. Funk proposed that the
polyneuritis arose because of a lack in the birds’ diet of a vital factor (now known to be thiamin) that could be found
in rice bran. Funk believed that some human diseases, particularly beriberi, scurvy, and pellagra, also were caused
by deficiencies of factors of the same chemical type. Because each of these factors had a nitrogen-containing
component known as an amine, he called the compounds “vital amines,” a term that he later shortened to
“vitamines.” The final e was dropped later when it was discovered that not all of the vitamins contain nitrogen and,
therefore, not all are amines.

In 1913 American researcher Elmer McCollum divided vitamins into two groups: “fat-soluble A” and “water-
soluble B.” As claims for the discovery of other vitamins multiplied, researchers called the new substances C, D,
and so on. Later it was realized that the water-soluble growth factor, vitamin B, was not a single entity but at least
two—only one of which prevented polyneuritis in pigeons. The factor required by pigeons was called vitamin B1,
and the other factor, essential for rats, was designated vitamin B2. As chemical structures of the vitamins became
known, they were also given chemical names, e.g., thiamin for vitamin B1 and riboflavin for vitamin B2.

Regulatory role

The vitamins regulate reactions that occur in metabolism, in contrast to other dietary components known as
macronutrients (e.g., fats, carbohydrates, proteins), which are the compounds utilized in the reactions regulated by
the vitamins. Absence of a vitamin blocks one or more specific metabolic reactions in a cell and eventually may
disrupt the metabolic balance within a cell and in the entire organism as well.
Britannica Stories
 34

With the exception of vitamin C (ascorbic acid), all of the water-soluble vitamins have a catalytic function; i.e., they
act as coenzymes of enzymes that function in energy transfer or in the metabolism of fats, carbohydrates, and
proteins. The metabolic importance of the water-soluble vitamins is reflected by their presence in most plant and
animal tissues involved in metabolism.

Some of the fat-soluble vitamins form part of the structure of biological membranes or assist in maintaining the
integrity (and therefore, indirectly, the function) of membranes. Some fat-soluble vitamins also may function at the
genetic level by controlling the synthesis of certain enzymes. Unlike the water-soluble ones, fat-soluble vitamins are
necessary for specific functions in highly differentiated and specialized tissues; therefore, their distribution in nature
tends to be more selective than that of the water-soluble vitamins.

Sources
Vitamins, which are found in all living organisms either because they are synthesized in the organism or are
acquired from the environment, are not distributed equally throughout nature. Some are absent from certain tissues
or species; for example, beta-carotene, which can be converted to vitamin A, is synthesized in plant tissues but not
in animal tissues. On the other hand, vitamins A and D3 (cholecalciferol) occur only in animal tissues. Both plants
and animals are important natural vitamin sources for human beings. Since vitamins are not distributed equally in
foodstuffs, the more restricted the diet of an individual, the more likely it is that he will lack adequate amounts of
one or more vitamins. Food sources of vitamin D are limited, but it can be synthesized in the skin through ultraviolet
radiation (from the Sun); therefore, with adequate exposure to sunlight, the dietary intake of vitamin D is of little
significance.

All vitamins can be either synthesized or produced commercially from food sources and are available for human
consumption in pharmaceutical preparations. Commercial processing of food (e.g., milling of grains) frequently
destroys or removes considerable amounts of vitamins. In most such instances, however, the vitamins are replaced
by chemical methods. Some foods are fortified with vitamins not normally present in them (e.g., vitamin D is added
to milk). Loss of vitamins may also occur when food is cooked; for instance, heat destroys vitamin A, and water-
soluble vitamins may be extracted from food to water and lost. Certain vitamins (e.g., B vitamins, vitamin K) can be
synthesized by microorganisms normally present in the intestines of some animals; however, the microorganisms
usually do not supply the host animal with an adequate quantity of a vitamin.

Requirements in living things

Vitamin requirements vary according to species, and the amount of a vitamin required by a specific organism is
difficult to determine because of the numerous factors (e.g., genetic variation, relative proportions of other dietary
constituents, environmental stresses). Although there is not uniform agreement concerning the human requirements
of vitamins, recommended daily vitamin intakes are sufficiently high to account for individual variation and normal
environmental stresses.

A number of interrelationships exist among vitamins and between vitamins and other dietary constituents. The
interactions may be synergistic (i.e., cooperative) or antagonistic, reflecting, for example, overlapping metabolic
roles (of the B vitamins in particular), protective roles (e.g., vitamins A and E), or structural dependency (e.g., cobalt
in the vitamin B12 molecule).

Results of deficiencies
Inadequate intake of a specific vitamin results in a characteristic deficiency disease (hypovitaminosis), the severity
of which depends upon the degree of vitamin deprivation. Symptoms may be specific (e.g., functional night
blindness of vitamin A deficiency) or nonspecific (e.g., loss of appetite, failure to grow). All symptoms for a specific
deficiency disease may not appear; in addition, the nature of the symptoms may vary with the species. Some effects
 35

of vitamin deficiencies cannot be reversed by adding the vitamin to the diet, especially if damage to nonregenerative
tissue (e.g., cornea of the eye, nerve tissue, calcified bone) has occurred.

A vitamin deficiency may be primary (or dietary), in which case the dietary intake is lower than the normal
requirement of the vitamin. A secondary (or conditioned) deficiency may occur (even though the dietary intake is
adequate) if a preexisting disease or state of stress is present (e.g., malabsorption of food from the intestine, chronic
alcoholism, repeated pregnancies and lactation). (More details on vitamin deficiencies in humans may be found in
nutritional disease.)

Evolution of vitamin-dependent organisms

Evolution of metabolic processes in primitive forms of life required the development of enzyme systems to catalyze
the complex sequences of chemical reactions involved in metabolism. In the beginning, the environment presumably
could supply all the necessary compounds (including the vitamin coenzymes); eventually, these compounds were
synthesized within an organism. As higher forms of life evolved, however, the ability to synthesize certain of these
vitamin coenzymes was gradually lost.

Since higher plants show no requirements for vitamins or other growth factors, it is assumed that they retain the
ability to synthesize them. Among insects, however, niacin, thiamin, riboflavin, vitamin B6, vitamin C, and
pantothenic acid are required by a few groups. All vertebrates, including humans, require dietary sources of vitamin
A, vitamin D, thiamin, riboflavin, vitamin B6, and pantothenic acid; some vertebrates, particularly the more highly
evolved ones, have additional requirements for other vitamins.

The water-soluble vitamins

Basic properties
Although the vitamins included in this classification are all water-soluble, the degree to which they dissolve in water
is variable. This property influences the route of absorption, their excretion, and their degree of tissue storage and
distinguishes them from fat-soluble vitamins, which are handled and stored differently by the body. The water-
soluble vitamins are vitamin C (ascorbic acid) and the B vitamins, which include thiamin (vitamin B1), riboflavin
(vitamin B2), vitamin B6, niacin (nicotinic acid), vitamin B12, folic acid, pantothenic acid, and biotin. These
relatively simple molecules contain the elements carbon, hydrogen, and oxygen; some also contain nitrogen, sulfur,
or cobalt.

The water-soluble vitamins, inactive in their so-called free states, must be activated to their coenzyme forms;
addition of phosphate groups occurs in the activation of thiamin, riboflavin, and vitamin B6; a shift in structure
activates biotin, and formation of a complex between the free vitamin and parts of other molecules is involved in the
activation of niacin, pantothenic acid, folic acid, and vitamin B12. After an active coenzyme is formed, it must
combine with the proper protein component (called an apoenzyme) before enzyme-catalyzed reactions can occur.

Functions
The B-vitamin coenzymes function in enzyme systems that transfer certain groups between molecules; as a result,
specific proteins, fats, and carbohydrates are formed and may be utilized to produce body tissues or to store or
release energy. The pantothenic acid coenzyme functions in the tricarboxylic acid cycle (also called the Krebs, or
citric acid, cycle), which interconnects carbohydrate, fat, and protein metabolism; this coenzyme (coenzyme A) acts
at the hub of these reactions and thus is an important molecule in controlling the interconversion of fats, proteins,
and carbohydrates and their conversion into metabolic energy. Thiamin and vitamin B6 coenzymes control the
conversion of carbohydrates and proteins respectively into metabolic energy during the citric acid cycle. Niacin and
riboflavin coenzymes facilitate the transfer of hydrogen ions or electrons (negatively charged particles), which
occurs during the reactions of the tricarboxylic acid cycle. All of these coenzymes also function in transfer reactions
that are involved in the synthesis of structural compounds; these reactions are not part of the tricarboxylic acid cycle.
 36

•
Functions of B-vitamin coenzymes in metabolism.

Encyclopædia Britannica, Inc.

Although vitamin C participates in some enzyme-catalyzed reactions, it has not yet been established that the vitamin
is a coenzyme. Its function probably is related to its properties as a strong reducing agent (i.e., it readily gives
electrons to other molecules).

Metabolism
The water-soluble vitamins are absorbed in the animal intestine, pass directly to the blood, and are carried to the
tissues in which they will be utilized. Vitamin B12 requires a substance known as intrinsic factor in order to be
absorbed.

Some of the B vitamins can occur in forms that cannot be used by an animal. Most of the niacin in some cereal
grains (wheat, corn, rice, barley, bran), for example, is bound to another substance, forming a complex called
niacytin that cannot be absorbed in the animal intestine. Biotin can be bound by the protein avidin, which is found in
raw egg white; this complex also cannot be absorbed or broken down by digestive-tract enzymes, and thus the biotin
cannot be utilized. In animal products (e.g., meat), biotin, vitamin B6, and folic acid are bound to other molecules to
form complexes or conjugated molecules; although none is active in the complex form, the three vitamins normally
are released from the bound forms by the enzymes of the intestinal tract (for biotin and vitamin B6) or in the tissues
(for folic acid) and thus can be utilized. The B vitamins are distributed in most metabolizing tissues of plants and
animals.

Water-soluble vitamins usually are excreted in the urine of humans. Thiamin, riboflavin, vitamin B6, vitamin C,
pantothenic acid, and biotin appear in urine as free vitamins (rather than as coenzymes); however, little free niacin is
excreted in the urine. Products (also called metabolites) that are formed during the metabolism of thiamin, niacin,
and vitamin B6 also appear in the urine. Urinary metabolites of biotin, riboflavin, and pantothenic acid also are
formed. Excretion of these vitamins (or their metabolites) is low when intake is sufficient for proper body function.
If intake begins to exceed minimal requirements, excess vitamins are stored in the tissues. Tissue storage capacity is
limited, however, and, as the tissues become saturated, the rate of excretion increases sharply. Unlike the other
water-soluble vitamins, however, vitamin B12 is excreted solely in the feces. Some folic acid and biotin also are
normally excreted in this way. Although fecal excretion of water-soluble vitamins (other than vitamin B12, folic acid,
and biotin) occurs, their source probably is the intestinal bacteria that synthesize the vitamins, rather than vitamins
that have been eaten and utilized by the animal.

The water-soluble vitamins generally are not considered toxic if taken in excessive amounts. There is, however, one
exception in humans: large amounts (50–100 mg; 1 mg = 0.001 gram) of niacin produce dilation of blood vessels; in
larger amounts, the effects are more serious and may result in impaired liver function. Thiamin given to animals in
amounts 100 times the requirement (i.e., about 100 mg) can cause death from respiratory failure. Therapeutic doses
(100–500 mg) of thiamin have no known toxic effects in humans (except rare instances of anaphylactic shock in
sensitive individuals). There is no known toxicity for any other B vitamins.

The fat-soluble vitamins

The four fat-soluble vitamin groups are A, D, E, and K; they are related structurally in that all have as a basic
structural unit of the molecule a five-carbon isoprene segment, which is

Each of the fat-soluble vitamin groups contains several related compounds that have biological activity. The potency
of the active forms in each vitamin group varies, and not all of the active forms now known are available from
 37

dietary sources; i.e., some are produced synthetically. The characteristics of each fat-soluble vitamin group are
discussed below.

Chemical properties
The chemical properties of fat-soluble vitamins determine their biological activities, functions, metabolism, and
excretion. However, while the substances in each group of fat-soluble vitamins are related in structure, indicating
that they share similar chemical properties, they do have important differences. These differences impart to the
vitamins unique qualities, chemical and biological, that affect attributes ranging from the manner in which the
vitamins are stored to the species in which they are active.

Vitamin A group
Ten carotenes, coloured molecules synthesized only in plants, show vitamin A activity; however, only the alpha- and
beta-carotenes and cryptoxanthin are important to humans, and beta-carotene is the most active. Retinol (vitamin A
alcohol) is considered the primary active form of the vitamin, although retinal, or vitamin A aldehyde, is the form
involved in the visual process in the retina of the eye. A metabolite of retinol with high biological activity may be an
even more direct active form than retinol. The ester form of retinol is the storage form of vitamin A; presumably, it
must be converted to retinol before it is utilized. Retinoic acid is a short-lived product of retinol; only retinoic acid
of the vitamin A group is not supplied by the diet.

Vitamin D group
Although about 10 compounds have vitamin D activity, the two most important ones are ergocalciferol (vitamin D2)
and cholecalciferol (vitamin D3). Vitamin D3 represents the dietary source, while vitamin D2 occurs in yeasts and
fungi. Both can be formed from their respective provitamins by ultraviolet irradiation; in humans and other animals
the provitamin (7-dehydrocholesterol), which is found in skin, can be converted by sunlight to vitamin D3 and thus is
an important source of the vitamin. Both vitamin D2 and vitamin D3 can be utilized by rats and humans; however,
chicks cannot use vitamin D2 effectively. The form of the vitamin probably active in humans is calcitriol.

Vitamin E group
The tocopherols are a closely related group of biologically active compounds that vary only in number and position
of methyl (−CH3) groups in the molecule; however, these structural differences influence the biological activity of
the various molecules. The active tocopherols are named in order of their potency; i.e., alpha-tocopherol is the most
active. Some metabolites of alpha-tocopherol (such as alpha-tocopherolquinone and alphatocopheronolactone) have
activity in some mammals (e.g., rats, rabbits); however, these metabolites do not support all the functions attributed
to vitamin E.

Vitamin K group
Vitamin K1 (20), or phylloquinone, is synthesized by plants; the members of the vitamin K2 (30), or menaquinone,
series are of microbial origin. Vitamin K2 (20) is the important form in mammalian tissue; all other forms are
converted to K2 (20) from vitamin K3 (menadione). Since vitamin K3 does not accumulate in tissue, it does not
furnish any dietary vitamin K.

Functions
The vitamin A group is essential for the maintenance of the linings of the body surfaces (e.g., skin, respiratory tract,
cornea), for sperm formation, and for the proper functioning of the immune system. In the retina of the eye, retinal is
combined with a protein called opsin; the complex molecules formed as a result of this combination and known as
rhodopsin (or visual purple) are involved in dark vision. The vitamin D group is required for growth (especially
bone growth or calcification). The vitamin E group also is necessary for normal animal growth; without vitamin E,
animals are not fertile and develop abnormalities of the central nervous system, muscles, and organs (especially the
 38

liver). The vitamin K group is required for normal metabolism, including the conversion of food into cellular energy
in certain biological membranes; vitamin K also is necessary for the proper clotting of blood.

Metabolism
The fat-soluble vitamins are transported primarily by lymph from the intestines to the circulating blood. Bile salts
are required for efficient absorption of fat-soluble metabolites in the intestine; anything that interferes with fat
absorption, therefore, also inhibits absorption of the fat-soluble vitamins. Since a fatty acid (preferentially palmitic
acid) is added to the retinol (vitamin A alcohol) molecule before it is transported by the lymph, this ester form
predominates in the bloodstream during digestion. Vitamins D, E, and K do not require the addition of a fatty acid
molecule for absorption. Small amounts of vitamin A (and possibly vitamin K) may be absorbed directly into the
bloodstream; however, both vitamins A and D are bound to a protein during transport in the bloodstream.

Larger quantities of the fat-soluble vitamins than of water-soluble ones can be stored in the body. Vitamins A, D,
and K are stored chiefly in the liver, with smaller amounts stored in other soft body tissues; however, most of the
stored vitamin E is found in body fat, although large amounts also occur in the uterus of females and testis of males.
The various forms of vitamin E are stored in tissues in different amounts; alpha-tocopherol is stored in higher
concentrations than are the other forms. More vitamin A is stored than any other fat-soluble vitamin.

Excessive intakes of both vitamins A and D may produce toxicity (or hypervitaminosis A or D). Toxicity of both
vitamin A and vitamin D can easily occur, however, if pharmaceutical vitamin preparations are used in excess.

Toxic levels of vitamin A exceed the normal requirement by 100 times—i.e., about 150,000 micrograms (μg; 1 μg =
0.000001 gram) each day for a period of several months. Toxicity in infants may occur with much smaller doses.
Excessive doses of the natural vitamins K1 and K2 have no obvious effects except that resistance may develop to
therapy with anticoagulant drugs; however, vitamin K3 is toxic to newborn infants if given in large doses. Vitamin
E, even if given in large excess of the normal requirement, has no apparent obvious adverse effects.

Vitamin groups E and K belong to a class of organic compounds called quinones. These substances are changed to
sugarlike substances known as alpha-lactones, which are excreted in the urine. Some vitamin K1 also is excreted in
the bile and thus appears in the feces. Vitamin A is broken down and excreted in bile (and, therefore, feces) and
urine. Vitamin D and its breakdown products are excreted only in the feces.

OUR LIFE DEPENDS ON MATTER

MATTER

Matter, material substance that constitutes the observable universe and, together with energy, forms the basis of all
objective phenomena.

At the most fundamental level, matter is composed of elementary particles, known as quarks and leptons (the class
of elementary particles that includes electrons). Quarks combine into protons and neutrons and, along with electrons,
form atoms of the elements of the periodic table, such as hydrogen, oxygen, and iron. Atoms may combine further
into molecules such as the water molecule, H2O. Large groups of atoms or molecules in turn form the bulk matter of
everyday life.

Depending on temperature and other conditions, matter may appear in any of several states. At ordinary
temperatures, for instance, gold is a solid, water is a liquid, and nitrogen is a gas, as defined by certain
characteristics: solids hold their shape, liquids take on the shape of the container that holds them, and gases fill an
entire container. These states can be further categorized into subgroups. Solids, for example, may be divided into
those with crystalline or amorphous structures or into metallic, ionic, covalent, or molecular solids, on the basis of
 39

the kinds of bonds that hold together the constituent atoms. Less-clearly defined states of matter include plasmas,
which are ionized gases at very high temperatures; foams, which combine aspects of liquids and solids; and clusters,
which are assemblies of small numbers of atoms or molecules that display both atomic-level and bulklike properties.

However, all matter of any type shares the fundamental property of inertia, which—as formulated within Isaac
Newton’s three laws of motion—prevents a material body from responding instantaneously to attempts to change its
state of rest or motion. The mass of a body is a measure of this resistance to change; it is enormously harder to set in
motion a massive ocean liner than it is to push a bicycle. Another universal property is gravitational mass, whereby
every physical entity in the universe acts so as to attract every other one, as first stated by Newton and later refined
into a new conceptual form by Albert Einstein.

Although basic ideas about matter trace back to Newton and even earlier to Aristotle’s natural philosophy, further
understanding of matter, along with new puzzles, began emerging in the early 20th century. Einstein’s theory of
special relativity (1905) shows that matter (as mass) and energy can be converted into each other according to the
famous equation E = mc2, where E is energy, m is mass, and c is the speed of light. This transformation occurs, for
instance, during nuclear fission, in which the nucleus of a heavy element such as uranium splits into two fragments
of smaller total mass, with the mass difference released as energy. Einstein’s theory of gravitation, also known as his
theory of general relativity (1916), takes as a central postulate the experimentally observed equivalence of inertial
mass and gravitational mass and shows how gravity arises from the distortions that matter introduces into the
surrounding space-time continuum.

The concept of matter is further complicated by quantum mechanics, whose roots go back to Max Planck’s
explanation in 1900 of the properties of electromagnetic radiation emitted by a hot body. In the quantum view,
elementary particles behave both like tiny balls and like waves that spread out in space—a seeming paradox that has
yet to be fully resolved. Additional complexity in the meaning of matter comes from astronomical observations that
began in the 1930s and that show that a large fraction of the universe consists of “dark matter.” This invisible
material does not affect light and can be detected only through its gravitational effects. Its detailed nature has yet to
be determined.

On the other hand, through the contemporary search for a unified field theory, which would place three of the four
types of interactions between elementary particles (the strong force, the weak force, and the electromagnetic force,
excluding only gravity) within a single conceptual framework, physicists may be on the verge of explaining the
origin of mass. Although a fully satisfactory grand unified theory (GUT) has yet to be derived, one component, the
electroweak theory of Sheldon Glashow, Abdus Salam, and Steven Weinberg (who shared the 1979 Nobel Prize for
Physics for this work) predicted that an elementary subatomic particle known as the Higgs boson imparts mass to all
known elementary particles. After years of experiments using the most powerful particle accelerators available,
scientists finally announced in 2012 the likely discovery of the Higgs boson.
(From Encyclopedia Britannica )

BUILDING BLOCKS OF LIFE

Living organisms are composed of organic compounds. In life they secrete or excrete organic materials into their
environment, shed body parts such as leaves and roots and after the organism dies, its body is broken down by
bacterial and fungal action. Larger molecules of organic matter can be formed from the polymerization of different
parts of already broken down matter. The composition of natural organic matter depends on its origin,
transformation mode, age, and existing environment, thus its bio-physico-chemical functions vary with different
environments.[4]
 40

n RNA and DNA are nucleic acids, and, along with proteins and carbohydrates, constitute the three major
macromolecules essential for all known forms of life.
n Ribonucleic acid (RNA) is a polymeric molecule implicated in various biological roles in coding,
decoding, regulation, and expression of genes.

n Amino acids are biologically important organic compounds containing amine (-NH2) and carboxylic acid
(-COOH) functional groups, usually along with a side-chain specific to each amino acid.
n The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen, though other elements are
found in the side-chains of certain amino acids.
n About 500 amino acids are known and can be classified in many ways.
n H+O= Water (H20)
n H+C (Hydrocarbon =petrolium, natural gas, Methane)
n H+O+C (Carbohydrate=Sugar)
n H+O+C+N = Protein (Amino acid)
n Amino-Acid =Amine (-NH2) + carboxylic acid (-COOH)

n What is DNA? (DNA=Deoxyribonucleic Acid)

n We all know that elephants only give birth to little elephants, giraffes to giraffes, dogs to dogs and so on for
every type of living creature. But why is this so?
The answer lies in a molecule called deoxyribonucleic acid (DNA), which contains the biological
instructions that make each species unique. DNA, along with the instructions it contains, is passed from
adult organisms to their offspring during reproduction.
n In organisms DNA is found inside a special area of the cell called the nucleus. Because the cell is very
small, and because organisms have many DNA molecules per cell, each DNA molecule must be tightly
packaged. This packaged form of the DNA is called a chromosome.
An organism's complete set of nuclear DNA is called its genome.
Besides the DNA located in the nucleus, humans and other complex organisms also have a small amount of
DNA in cell structures known as mitochondria. Mitochondria generate the energy the cell needs to function
properly.
In sexual reproduction, organisms inherit half of their nuclear DNA from the male parent and half from the
female parent. However, organisms inherit all of their mitochondrial DNA from the female parent. This
occurs because only egg cells, and not sperm cells, keep their mitochondria during fertilization.

n What is DNA made of?

n DNA is made of chemical building blocks called nucleotides. These building blocks are made of three
parts: a phosphate group, a sugar group and one of four types of nitrogen bases. To form a strand of DNA,
nucleotides are linked into chains, with the phosphate and sugar groups alternating.

The four types of nitrogen bases found in nucleotides are: adenine (A), thymine (T), guanine (G) and
cytosine (C). The order, or sequence, of these bases determines what biological instructions are contained
in a strand of DNA. For example, the sequence ATCGTT might instruct for blue eyes, while ATCGCT
might instruct for brown.

The complete DNA instruction book, or genome, for a human contains about 3 billion bases and about
20,000 genes on 23 pairs of chromosomes.
n What does DNA do?
n DNA contains the instructions needed for an organism to develop, survive and reproduce. To carry out
these functions, DNA sequences must be converted into messages that can be used to produce proteins,
which are the complex molecules that do most of the work in our bodies.
Each DNA sequence that contains instructions to make a protein is known as a gene. The size of a gene
may vary greatly, ranging from about 1,000 bases to 1 million bases in humans. Genes only make up about
 41

1 percent of the DNA sequence. DNA sequences outside this 1 percent are involved in regulating when,
how and how much of a protein is made.

n Everything in life needs protein to live,

n and vegetables can be a great source of protein.
n Protein is a macro nutrient necessary for the proper growth and function of the human body. There is
considerable debate over the amount of protein a person needs to consume per day, the current
recommended daily intake (RDI) for protein is 46 grams for women aged 19-70, and 56 grams for men
aged 19-70. Any excess protein is turned into energy by the body, and it is controversial whether this
excess protein causes a strain on the liver.
n A deficiency in protein leads to muscle atrophy, and impaired functioning of the human body in general.
n High protein foods include meat, fish, cheese, tofu, beans, lentils, yogurt, eggs, nuts, and seeds.
n Our Genome: Humans only have around 24,000 genes. large parts of our genome is made up of DNA that
doesn’t code for genes.
n The human genome is the complete set of nucleic acid sequence for humans (Homo sapiens), encoded as
DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual
mitochondria. Human genomes include both protein-coding DNA genes and noncoding DNA.
n RNA and DNA are nucleic acids, and, along with proteins and carbohydrates, constitute the three major
macromolecules essential for all known forms of life.
n Ribonucleic acid (RNA) is a polymeric molecule implicated in various biological roles in coding,
decoding, regulation, and expression of genes.
n STRUCTURE
n Each nucleotide in RNA contains a ribose sugar, with carbons numbered 1' through 5'. A base is attached to
the 1' position, in general, adenine (A), cytosine (C), guanine (G), or uracil (U). A phosphate group is
attached to the 3' position of one ribose and the 5' position of the next. The phosphate groups do not have a
negative charge each at physiological pH, making RNA a charged molecule (polyanion). The bases form
hydrogen bonds between cytosine and guanine, between adenine and uracil and between guanine and
uracil.[8] However, other interactions are possible, such as a group of adenine bases binding to each other in
a bulge,[9] or the GNRA tetraloopthat has a guanine–adenine base-pair.[8]

PROTEINS

Protein, highly complex substance that is present in all living organisms. Proteins are of great nutritional value and
are directly involved in the chemical processes essential for life. The importance of proteins was recognized by
chemists in the early 19th century, including Swedish chemist Jöns Jacob Berzelius, who in 1838 coined the term
protein, a word derived from the Greek proteios, meaning “holding first place.” Proteins are species-specific; that is,
the proteins of one species differ from those of another species. They are also organ-specific; for instance, within a
single organism, muscle proteins differ from those of the brain and liver.

A protein molecule is very large compared with molecules of sugar or salt and consists of many amino acids joined
together to form long chains, much as beads are arranged on a string. There are about 20 different amino acids that
occur naturally in proteins. Proteins of similar function have similar amino acid composition and sequence.
Although it is not yet possible to explain all of the functions of a protein from its amino acid sequence, established
correlations between structure and function can be attributed to the properties of the amino acids that compose
proteins.

Plants can synthesize all of the amino acids; animals cannot, even though all of them are essential for life. Plants can
grow in a medium containing inorganic nutrients that provide nitrogen, potassium, and other substances essential for
growth. They utilize the carbon dioxide in the air during the process of photosynthesis to form organic compounds
such as carbohydrates. Animals, however, must obtain organic nutrients from outside sources. Because the protein
content of most plants is low, very large amounts of plant material are required by animals, such as ruminants (e.g.,
 42

cows), that eat only plant material to meet their amino acid requirements. Nonruminant animals, including humans,
obtain proteins principally from animals and their products—e.g., meat, milk, and eggs. The seeds of legumes are
increasingly being used to prepare inexpensive protein-rich food (see human nutrition).

The protein content of animal organs is usually much higher than that of the blood plasma. Muscles, for example,
contain about 30 percent protein, the liver 20 to 30 percent, and red blood cells 30 percent. Higher percentages of
protein are found in hair, bones, and other organs and tissues with a low water content. The quantity of free amino
acids and peptides in animals is much smaller than the amount of protein; protein molecules are produced in cells by
the stepwise alignment of amino acids and are released into the body fluids only after synthesis is complete.

The high protein content of some organs does not mean that the importance of proteins is related to their amount in
an organism or tissue; on the contrary, some of the most important proteins, such as enzymes and hormones, occur
in extremely small amounts. The importance of proteins is related principally to their function. All enzymes
identified thus far are proteins. Enzymes, which are the catalysts of all metabolic reactions, enable an organism to
build up the chemical substances necessary for life—proteins, nucleic acids, carbohydrates, and lipids—to convert
them into other substances, and to degrade them. Life without enzymes is not possible. There are several protein
hormones with important regulatory functions. In all vertebrates, the respiratory protein hemoglobin acts as oxygen
carrier in the blood, transporting oxygen from the lung to body organs and tissues. A large group of structural
proteins maintains and protects the structure of the animal body.

General structure and properties of proteins

The amino acid composition of proteins

The common property of all proteins is that they consist of long chains of α-amino (alpha amino) acids. The general
structure of α-amino acids is shown in . The α-amino acids are so called because the α-carbon atom in the molecule
carries an amino group (−NH2); the α-carbon atom also carries a carboxyl group (−COOH).

In acidic solutions, when the pH is less than 4, the −COO groups combine with hydrogen ions (H+) and are thus
converted into the uncharged form (−COOH). In alkaline solutions, at pH above 9, the ammonium groups (−NH+3)
lose a hydrogen ion and are converted into amino groups (−NH2). In the pH range between 4 and 8, amino acids
carry both a positive and a negative charge and therefore do not migrate in an electrical field. Such structures have
been designated as dipolar ions, or zwitterions (i.e., hybrid ions).

Although more than 100 amino acids occur in nature, particularly in plants, only 20 types are commonly found in
most proteins. In protein molecules the α-amino acids are linked to each other by peptide bonds between the amino
group of one amino acid and the carboxyl group of its neighbour.

The condensation (joining) of three amino acids yields the tripeptide.

It is customary to write the structure of peptides in such a way that the free α-amino group (also called the N
terminus of the peptide) is at the left side and the free carboxyl group (the C terminus) at the right side. Proteins are
macromolecular polypeptides—i.e., very large molecules composed of many peptide-bonded amino acids. Most of
the common ones contain more than 100 amino acids linked to each other in a long peptide chain. The average
molecular weight (based on the weight of a hydrogen atom as 1) of each amino acid is approximately 100 to 125;
thus, the molecular weights of proteins are usually in the range of 10,000 to 100,000 daltons (one dalton is the
weight of one hydrogen atom). The species-specificity and organ-specificity of proteins result from differences in
the number and sequences of amino acids. Twenty different amino acids in a chain 100 amino acids long can be
arranged in far more than 10100 ways (10100 is the number one followed by 100 zeroes).
 43

Structures of common amino acids

The amino acids present in proteins differ from each other in the structure of their side (R) chains. The simplest
amino acid is glycine, in which R is a hydrogen atom. In a number of amino acids, R represents straight or branched
carbon chains. One of these amino acids is alanine, in which R is the methyl group (−CH3). Valine, leucine, and
isoleucine, with longer R groups, complete the alkyl side-chain series. The alkyl side chains (R groups) of these
amino acids are nonpolar; this means that they have no affinity for water but some affinity for each other. Although
plants can form all of the alkyl amino acids, animals can synthesize only alanine and glycine; thus valine, leucine,
and isoleucine must be supplied in the diet.

Two amino acids, each containing three carbon atoms, are derived from alanine; they are serine and cysteine. Serine
contains an alcohol group (−CH2OH) instead of the methyl group of alanine, and cysteine contains a mercapto group
(−CH2SH). Animals can synthesize serine but not cysteine or cystine. Cysteine occurs in proteins predominantly in
its oxidized form (oxidation in this sense meaning the removal of hydrogen atoms), called cystine. Cystine consists
of two cysteine molecules linked by the disulfide bond (−S−S−) that results when a hydrogen atom is removed from
the mercapto group of each of the cysteines. Disulfide bonds are important in protein structure because they allow
the linkage of two different parts of a protein molecule to—and thus the formation of loops in—the otherwise
straight chains. Some proteins contain small amounts of cysteine with free sulfhydryl (−SH) groups.

Four amino acids, each consisting of four carbon atoms, occur in proteins; they are aspartic acid, asparagine,
threonine, and methionine. Aspartic acid and asparagine, which occur in large amounts, can be synthesized by
animals. Threonine and methionine cannot be synthesized and thus are essential amino acids; i.e., they must be
supplied in the diet. Most proteins contain only small amounts of methionine.

Proteins also contain an amino acid with five carbon atoms (glutamic acid) and a secondary amine (in proline),
which is a structure with the amino group (−NH2) bonded to the alkyl side chain, forming a ring. Glutamic acid and
aspartic acid are dicarboxylic acids; that is, they have two carboxyl groups (−COOH).

Glutamine is similar to asparagine in that both are the amides of their corresponding dicarboxylic acid forms; i.e.,
they have an amide group (−CONH2) in place of the carboxyl (−COOH) of the side chain. Glutamic acid and
glutamine are abundant in most proteins; e.g., in plant proteins they sometimes comprise more than one-third of the
amino acids present. Both glutamic acid and glutamine can be synthesized by animals.
Amino acid content of some proteins
protein
collagen keratin
amino acid* alpha-casein gliadin edestin myosin
(ox hide) (wool)
lysine 60.9 4.45 19.9 27.4 6.2 85
histidine 18.7 11.7 18.6 4.5 19.7 15
arginine 24.7 15.7 99.2 47.1 56.9 41
aspartic acid** 63.1 10.1 99.4 51.9 51.5 85
threonine 41.2 17.6 31.2 19.3 55.9 41
serine 63.1 46.7 55.7 41.0 79.5 41
glutamic acid** 153.1 311.0 144.9 76.2 99.0 155
proline 71.3 117.8 32.9 125.2 58.3 22
glycine 37.3 — 68.0 354.6 78.0 39
alanine 41.5 23.9 57.7 115.7 43.8 78
half-cystine 3.6 21.3 10.9 0.0 105.0 86
valine 53.8 22.7 54.6 21.4 46.6 42
 44

methionine 16.8 11.3 16.4 6.5 4.0 22

isoleucine 48.8 90.8*** 41.9 14.5 29.0 42
leucine 60.3 60.0 28.2 59.9 79
tyrosine 44.7 17.7 26.9 5.5 28.7 18
phenylalanine 27.9 39.0 38.4 13.9 22.4 27
tryptophan 7.8 3.2 6.6 0.0 9.6 —
hydroxyproline 0.0 0.0 0.0 97.5 12.2 —
hydroxylysine — — — 8.0 1.2 —
total 839 765 883 1,058 863 832
average residual weight 119 131 113 95 117 120
*Number of gram molecules of amino acid per 100,000 grams of protein.
**The values for aspartic acid and glutamic acid include asparagine and glutamine, respectively.
***Isoleucine plus leucine.
The amino acids proline and hydroxyproline occur in large amounts in collagen, the protein of the connective tissue
of animals. Proline and hydroxyproline lack free amino (−NH2) groups because the amino group is enclosed in a
ring structure with the side chain; they thus cannot exist in a zwitterion form. Although the nitrogen-containing
group (>NH) of these amino acids can form a peptide bond with the carboxyl group of another amino acid, the bond
so formed gives rise to a kink in the peptide chain; i.e., the ring structure alters the regular bond angle of normal
peptide bonds.

Proteins usually are almost neutral molecules; that is, they have neither acidic nor basic properties. This means that
the acidic carboxyl ( −COO−) groups of aspartic and glutamic acid are about equal in number to the amino acids
with basic side chains. Three such basic amino acids, each containing six carbon atoms, occur in proteins. The one
with the simplest structure, lysine, is synthesized by plants but not by animals. Even some plants have a low lysine
content. Arginine is found in all proteins; it occurs in particularly high amounts in the strongly basic protamines
(simple proteins composed of relatively few amino acids) of fish sperm. The third basic amino acid is histidine. Both
arginine and histidine can be synthesized by animals. Histidine is a weaker base than either lysine or arginine. The
imidazole ring, a five-membered ring structure containing two nitrogen atoms in the side chain of histidine, acts as a
buffer (i.e., a stabilizer of hydrogen ion concentration) by binding hydrogen ions (H+) to the nitrogen atoms of the
imidazole ring.

The remaining amino acids—phenylalanine, tyrosine, and tryptophan—have in common an aromatic structure; i.e.,
a benzene ring is present. These three amino acids are essential, and, while animals cannot synthesize the benzene
ring itself, they can convert phenylalanine to tyrosine.

Because these amino acids contain benzene rings, they can absorb ultraviolet light at wavelengths between 270 and
290 nanometres (nm; 1 nanometre = 10−9 metre = 10 angstrom units). Phenylalanine absorbs very little ultraviolet
light; tyrosine and tryptophan, however, absorb it strongly and are responsible for the absorption band most proteins
exhibit at 280–290 nanometres. This absorption is often used to determine the quantity of protein present in protein
samples.

Most proteins contain only the amino acids described above; however, other amino acids occur in proteins in small
amounts. For example, the collagen found in connective tissue contains, in addition to hydroxyproline, small
amounts of hydroxylysine. Other proteins contain some monomethyl-, dimethyl-, or trimethyllysine—i.e., lysine
derivatives containing one, two, or three methyl groups (−CH3). The amount of these unusual amino acids in
proteins, however, rarely exceeds 1 or 2 percent of the total amino acids.
 45

Physicochemical properties of the amino acids

The physicochemical properties of a protein are determined by the analogous properties of the amino acids in it.

The α-carbon atom of all amino acids, with the exception of glycine, is asymmetric; this means that four different
chemical entities (atoms or groups of atoms) are attached to it. As a result, each of the amino acids, except glycine,
can exist in two different spatial, or geometric, arrangements (i.e., isomers), which are mirror images akin to right
and left hands.

These isomers exhibit the property of optical rotation. Optical rotation is the rotation of the plane of polarized light,
which is composed of light waves that vibrate in one plane, or direction, only. Solutions of substances that rotate the
plane of polarization are said to be optically active, and the degree of rotation is called the optical rotation of the
solution. The direction in which the light is rotated is generally designed as plus, or d, for dextrorotatory (to the
right), or as minus, or l, for levorotatory (to the left). Some amino acids are dextrorotatory, others are levorotatory.
With the exception of a few small proteins (peptides) that occur in bacteria, the amino acids that occur in proteins
are l-amino acids.

In bacteria, d-alanine and some other d-amino acids have been found as components of gramicidin and bacitracin.
These peptides are toxic to other bacteria and are used in medicine as antibiotics. The d-alanine has also been found
in some peptides of bacterial membranes.

In contrast to most organic acids and amines, the amino acids are insoluble in organic solvents. In aqueous solutions
they are dipolar ions (zwitterions, or hybrid ions) that react with strong acids or bases in a way that leads to the
neutralization of the negatively or positively charged ends, respectively. Because of their reactions with strong acids
and strong bases, the amino acids act as buffers—stabilizers of hydrogen ion (H+) or hydroxide ion (OH−)
concentrations. In fact, glycine is frequently used as a buffer in the pH range from 1 to 3 (acid solutions) and from 9
to 12 (basic solutions). In acid solutions, glycine has a positive charge and therefore migrates to the cathode
(negative electrode of a direct-current electrical circuit with terminals in the solution). Its charge, however, is
negative in alkaline solutions, in which it migrates to the anode (positive electrode). At pH 6.1 glycine does not
migrate, because each molecule has one positive and one negative charge. The pH at which an amino acid does not
migrate in an electrical field is called the isoelectric point. Most of the monoamino acids (i.e., those with only one
amino group) have isoelectric points similar to that of glycine. The isoelectric points of aspartic and glutamic acids,
however, are close to pH 3, and those of histidine, lysine, and arginine are at pH 7.6, 9.7, and 10.8, respectively.

Amino acid sequence in protein molecules

Since each protein molecule consists of a long chain of amino acid residues, linked to each other by peptide bonds,
the hydrolytic cleavage of all peptide bonds is a prerequisite for the quantitative determination of the amino acid
residues. Hydrolysis is most frequently accomplished by boiling the protein with concentrated hydrochloric acid.
The quantitative determination of the amino acids is based on the discovery that amino acids can be separated from
each other by chromatography on filter paper and made visible by spraying the paper with ninhydrin. The amino
acids of the protein hydrolysate are separated from each other by passing the hydrolysate through a column of
adsorbents, which adsorb the amino acids with different affinities and, on washing the column with buffer solutions,
release them in a definite order. The amount of each of the amino acids can be determined by the intensity of the
colour reaction with ninhydrin.

To obtain information about the sequence of the amino acid residues in the protein, the protein is degraded stepwise,
one amino acid being split off in each step. This is accomplished by coupling the free α-amino group (−NH2) of the
N-terminal amino acid with phenyl isothiocyanate; subsequent mild hydrolysis does not affect the peptide bonds.
The procedure, called the Edman degradation, can be applied repeatedly; it thus reveals the sequence of the amino
acids in the peptide chain.
 46

Unavoidable small losses that occur during each step make it impossible to determine the sequence of more than
about 30 to 50 amino acids by this procedure. For this reason the protein is usually first hydrolyzed by exposure to
the enzyme trypsin, which cleaves only peptide bonds formed by the carboxyl groups of lysine and arginine. The
Edman degradation is then applied to each of the few resulting peptides produced by the action of trypsin. Further
information can be gained by hydrolyzing another portion of the protein with another enzyme, for instance with
chymotrypsin, which splits predominantly peptide bonds formed by the amino acids tyrosine, phenylalanine, and
tryptophan. The combination of results obtained with two or more different proteolytic (protein degrading) enzymes
was first applied by English biochemist Frederick Sanger, and it enabled him to elucidate the amino acid sequence
of insulin. The amino acid sequences of many other proteins subsequently were determined in the same manner.

Levels of structural organization in proteins

Primary structure
Analytical and synthetic procedures reveal only the primary structure of the proteins—that is, the amino acid
sequence of the peptide chains. They do not reveal information about the conformation (arrangement in space) of the
peptide chain—that is, whether the peptide chain is present as a long straight thread or is irregularly coiled and
folded into a globule. The configuration, or conformation, of a protein is determined by mutual attraction or
repulsion of polar or nonpolar groups in the side chains (R groups) of the amino acids. The former have positive or
negative charges in their side chains; the latter repel water but attract each other. Some parts of a peptide chain
containing 100 to 200 amino acids may form a loop, or helix; others may be straight or form irregular coils.

The terms secondary, tertiary, and quaternary structure are frequently applied to the configuration of the peptide
chain of a protein. A nomenclature committee of the International Union of Biochemistry (IUB) has defined these
terms as follows: The primary structure of a protein is determined by its amino acid sequence without any regard for
the arrangement of the peptide chain in space. The secondary structure is determined by the spatial arrangement of
the main peptide chain without any regard for the conformation of side chains or other segments of the main chain.
The tertiary structure is determined by both the side chains and other adjacent segments of the main chain, without
regard for neighbouring peptide chains. Finally, the term quaternary structure is used for the arrangement of
identical or different subunits of a large protein in which each subunit is a separate peptide chain.

Secondary structure
The nitrogen and carbon atoms of a peptide chain cannot lie on a straight line, because of the magnitude of the bond
angles between adjacent atoms of the chain; the bond angle is about 110°. Each of the nitrogen and carbon atoms
can rotate to a certain extent, however, so that the chain has a limited flexibility. Because all of the amino acids,
except glycine, are asymmetric l-amino acids, the peptide chain tends to assume an asymmetric helical shape; some
of the fibrous proteins consist of elongated helices around a straight screw axis. Such structural features result from
properties common to all peptide chains. The product of their effects is the secondary structure of the protein.

Tertiary structure
The tertiary structure is the product of the interaction between the side chains (R) of the amino acids composing the
protein. Some of them contain positively or negatively charged groups, others are polar, and still others are
nonpolar. The number of carbon atoms in the side chain varies from zero in glycine to nine in tryptophan. Positively
and negatively charged side chains have the tendency to attract each other; side chains with identical charges repel
each other. The bonds formed by the forces between the negatively charged side chains of aspartic or glutamic acid
on the one hand, and the positively charged side chains of lysine or arginine on the other hand, are called salt
bridges. Mutual attraction of adjacent peptide chains also results from the formation of numerous hydrogen bonds.
 47

Hydrogen bonds form as a result of the attraction between the nitrogen-bound hydrogen atom (the imide hydrogen)
and the unshared pair of electrons of the oxygen atom in the double bonded carbon–oxygen group (the carbonyl
group). The result is a slight displacement of the imide hydrogen toward the oxygen atom of the carbonyl group.
Although the hydrogen bond is much weaker than a covalent bond (i.e., the type of bond between two carbon atoms,
which equally share the pair of bonding electrons between them), the large number of imide and carbonyl groups in
peptide chains results in the formation of numerous hydrogen bonds. Another type of attraction is that between
nonpolar side chains of valine, leucine, isoleucine, and phenylalanine; the attraction results in the displacement of
water molecules and is called hydrophobic interaction.

In proteins rich in cystine, the conformation of the peptide chain is determined to a considerable extent by the
disulfide bonds (−S−S−) of cystine. The halves of cystine may be located in different parts of the peptide chain and
thus may form a loop closed by the disulfide bond.

If the disulfide bond is reduced (i.e., hydrogen is added) to two sulfhydryl (−SH) groups, the tertiary structure of the
protein undergoes a drastic change—closed loops are broken and adjacent disulfide-bonded peptide chains separate.

Quaternary structure
The nature of the quaternary structure is demonstrated by the structure of hemoglobin. Each molecule of human
hemoglobin consists of four peptide chains, two α-chains and two β-chains; i.e., it is a tetramer. The four subunits
are linked to each other by hydrogen bonds and hydrophobic interaction. Because the four subunits are so closely
linked, the hemoglobin tetramer is called a molecule, even though no covalent bonds occur between the peptide
chains of the four subunits. In other proteins, the subunits are bound to each other by covalent bonds (disulfide
bridges).

The amino acid sequence of porcine proinsulin is shown below. The arrows indicate the direction from the N

terminus of the β-chain (B) to the C terminus of the α-chain (A).

The isolation and determination of proteins

Animal material usually contains large amounts of protein and lipids and small amounts of carbohydrate; in plants,
the bulk of the dry matter is usually carbohydrate. If it is necessary to determine the amount of protein in a mixture
of animal foodstuffs, a sample is converted to ammonium salts by boiling with sulfuric acid and a suitable inorganic
catalyst, such as copper sulfate (Kjeldahl method). The method is based on the assumption that proteins contain 16
percent nitrogen, and that nonprotein nitrogen is present in very small amounts. The assumption is justified for most
tissues from higher animals but not for insects and crustaceans, in which a considerable portion of the body nitrogen
is present in the form of chitin, a carbohydrate. Large amounts of nonprotein nitrogen are also found in the sap of
many plants. In such cases, the precise quantitative analyses are made after the proteins have been separated from
other biological compounds.

Proteins are sensitive to heat, acids, bases, organic solvents, and radiation exposure; for this reason, the chemical
methods employed to purify organic compounds cannot be applied to proteins. Salts and molecules of small size are
removed from protein solutions by dialysis—i.e., by placing the solution into a sac of semipermeable material, such
as cellulose or acetylcellulose, which will allow small molecules to pass through but not large protein molecules,
and immersing the sac in water or a salt solution. Small molecules can also be removed either by passing the protein
solution through a column of resin that adsorbs only the protein or by gel filtration. In gel filtration, the large protein
molecules pass through the column, and the small molecules are adsorbed to the gel.

Groups of proteins are separated from each other by salting out—i.e., the stepwise addition of sodium sulfate or
ammonium sulfate to a protein solution. Some proteins, called globulins, become insoluble and precipitate when the
solution is half-saturated with ammonium sulfate or when its sodium sulfate content exceeds about 12 percent. Other
proteins, the albumins, can be precipitated from the supernatant solution (i.e., the solution remaining after a
 48

precipitation has taken place) by saturation with ammonium sulfate. Water-soluble proteins can be obtained in a dry
state by freeze-drying (lyophilization), in which the protein solution is deep-frozen by lowering the temperature
below −15 °C (5 °F) and removing the water; the protein is obtained as a dry powder.

Most proteins are insoluble in boiling water and are denatured by it—i.e., irreversibly converted into an insoluble
material. Heat denaturation cannot be used with connective tissue because the principal structural protein, collagen,
is converted by boiling water into water-soluble gelatin.

Fractionation (separation into components) of a mixture of proteins of different molecular weight can be
accomplished by gel filtration. The size of the proteins retained by the gel depends upon the properties of the gel.
The proteins retained in the gel are removed from the column by solutions of a suitable concentration of salts and
hydrogen ions.

Many proteins were originally obtained in crystalline form, but crystallinity is not proof of purity; many crystalline
protein preparations contain other substances. Various tests are used to determine whether a protein preparation
contains only one protein. The purity of a protein solution can be determined by such techniques as chromatography
and gel filtration. In addition, a solution of pure protein will yield one peak when spun in a centrifuge at very high
speeds (ultracentrifugation) and will migrate as a single band in electrophoresis (migration of the protein in an
electrical field). After these methods and others (such as amino acid analysis) indicate that the protein solution is
pure, it can be considered so. Because chromatography, ultracentrifugation, and electrophoresis cannot be applied to
insoluble proteins, little is known about them; they may be mixtures of many similar proteins.

Very small (microheterogeneous) differences in some of the apparently pure proteins are known to occur. They are
differences in the amino acid composition of otherwise identical proteins and are transmitted from generation to
generation; i.e., they are genetically determined. For example, some humans have two hemoglobins, hemoglobin A
and hemoglobin S, which differ in one amino acid at a specific site in the molecule. In hemoglobin A the site is
occupied by glutamic acid and in hemoglobin S by valine. Refinement of the techniques of protein analysis has
resulted in the discovery of other instances of microheterogeneity.
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The quantity of a pure protein can be determined by weighing or by measuring the ultraviolet absorbancy at 280
nanometres. The absorbency at 280 nanometres depends on the content of tyrosine and tryptophan in the protein.
Sometimes the slightly less sensitive biuret reaction, a purple colour given by alkaline protein solutions upon the
addition of copper sulfate, is used; its intensity depends only on the number of peptide bonds per gram, which is
similar in all proteins.

Physicochemical properties of proteins

The molecular weight of proteins

The molecular weight of proteins cannot be determined by the methods of classical chemistry (e.g., freezing-point
depression), because they require solutions of a higher concentration of protein than can be prepared.

If a protein contains only one molecule of one of the amino acids or one atom of iron, copper, or another element,
the minimum molecular weight of the protein or a subunit can be calculated; for example, the protein myoglobin
contains 0.34 gram of iron in 100 grams of protein. The atomic weight of iron is 56; thus the minimum molecular
weight of myoglobin is (56 × 100)/0.34 = about 16,500. Direct measurements of the molecular weight of myoglobin
yield the same value. The molecular weight of hemoglobin, however, which also contains 0.34 percent iron, has
been found to be 66,000 or 4 × 16,500; thus hemoglobin contains four atoms of iron.

The method most frequently used to determine the molecular weight of proteins is ultracentrifugation—i.e., spinning
in a centrifuge at velocities up to about 60,000 revolutions per minute. Centrifugal forces of more than 200,000
times the gravitational force on the surface of Earth are achieved at such velocities. The first ultracentrifuges, built
 49

in 1920, were used to determine the molecular weight of proteins. The molecular weights of a large number of
proteins have been determined. Most consist of several subunits, the molecular weight of which is usually less than
100,000 and frequently ranges from 20,000 to 30,000. Proteins of very high molecular weights are found among
hemocyanins, the copper-containing respiratory proteins of invertebrates; some range as high as several million.
Although there is no definite lower limit for the molecular weight of proteins, short amino acid sequences are
usually called peptides.
Number of amino acids per protein molecule
protein*
amino acid Cyto Hb alpha Hb beta RNase Lys Chgen Fdox
lysine 18 11 11 10 6 14 4
histidine 3 10 9 4 1 2 1
arginine 2 3 3 4 11 4 1
aspartic acid** 8 12 13 15 21 23 13
threonine 7 9 7 10 7 23 8
serine 2 11 5 15 10 28 7
glutamic acid** 10 5 11 12 5 15 13
proline 4 7 7 4 2 9 4
glycine 13 7 13 3 12 23 6
alanine 6 21 15 12 12 22 9
half-cystine 2 1 2 8 8 10 5
valine 3 13 18 9 6 23 7
methionine 3 2 1 4 2 2 0
isoleucine 8 0 0 3 6 10 4
leucine 6 18 18 2 8 19 8
tyrosine 5 3 3 6 3 4 4
phenylalanine 3 7 8 3 3 6 2
tryptophan 1 1 2 0 6 8 1
total 104 141 146 124 129 245 97
*Cyto = human cytochrome c; Hb alpha = human hemoglobin A, alpha-chain; Hb beta = human hemoglobin A,
beta-chain; RNase = bovine ribonuclease; Lys = chicken lysozyme; Chgen = bovine chymotrypsinogen; Fdox =
spinach ferredoxin.
**The values recorded for aspartic acid and glutamic acid include asparagine and glutamine, respectively.

Classification by biological functions

In view of the unsatisfactory state of the old classification, it is preferable to classify the proteins according to their
biological function. Such a classification is far from ideal, however, because one protein can have more than one
function. The contractile protein myosin, for example, also acts as an ATPase (adenosine triphosphatase), an enzyme
that hydrolyzes adenosine triphosphate (removes a phosphate group from ATP by introducing a water molecule).
Another problem with functional classification is that the definite function of a protein frequently is not known. A
protein cannot be called an enzyme as long as its substrate (the specific compound upon which it acts) is not known.
It cannot even be tested for its enzymatic action when its substrate is not known.
 50

Special structure and function of proteins

Despite its weaknesses, a functional classification is used here in order to demonstrate, whenever possible, the
correlation between the structure and function of a protein. The structural, fibrous proteins are presented first,
because their structure is simpler than that of the globular proteins and more clearly related to their function, which
is the maintenance of either a rigid or a flexible structure.

Structural proteins

Scleroproteins

Collagen
Collagen is the structural protein of bones, tendons, ligaments, and skin. For many years collagen was considered to
be insoluble in water. Part of the collagen of calf skin, however, can be extracted with citrate buffer at pH 3.7. A
precursor of collagen called procollagen is converted in the body into collagen. Procollagen has a molecular weight
of 120,000. Cleavage of one or a few peptide bonds of procollagen yields collagen, which has three subunits, each
with a molecular weight of 95,000; therefore, the molecular weight of collagen is 285,000 (3 × 95,000). The three
subunits are wound as spirals around an elongated straight axis. The length of each subunit is 2,900 angstroms, and
its diameter is approximately 15 angstroms. The three chains are staggered, so that the trimer has no definite
terminal limits.

Collagen differs from all other proteins in its high content of proline and hydroxyproline. Hydroxyproline does not
occur in significant amounts in any other protein except elastin. Most of the proline in collagen is present in the
sequence glycine–proline-X, in which X is frequently alanine or hydroxyproline. Collagen does not contain cystine
or tryptophan and therefore cannot substitute for other proteins in the diet. The presence of proline causes kinks in
the peptide chain and thus reduces the length of the amino acid unit from 3.7 angstroms in the extended chain of the
β-structure to 2.86 angstroms in the collagen chain. In the intertwined triple helix, the glycines are inside, close to
the axis; the prolines are outside.

Native collagen resists the action of trypsin but is hydrolyzed by the bacterial enzyme collagenase. When collagen is
boiled with water, the triple helix is destroyed, and the subunits are partially hydrolyzed; the product is gelatin. The
unfolded peptide chains of gelatin trap large amounts of water, resulting in a hydrated molecule.

When collagen is treated with tannic acid or with chromium salts, cross links form between the collagen fibres, and
it becomes insoluble; the conversion of hide into leather is based on this tanning process. The tanned material is
insoluble in hot water and cannot be converted to gelatin. On exposure to water at 62° to 63° C (144° to 145° F),
however, the cross links formed by the tanning agents collapse, and the leather contracts irreversibly to about one-
third its original volume.
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Collagen seems to undergo an aging process in living organisms that may be caused by the formation of cross links
between collagen fibres. They are formed by the conversion of some lysine side chains to aldehydes (compounds
with the general structure RCHO), and the combination of the aldehydes with the ε-amino groups of intact lysine
side chains. The protein elastin, which occurs in the elastic fibres of connective tissue, contains similar cross links
and may result from the combination of collagen fibres with other proteins. When cross-linked collagen or elastin is
degraded, products of the cross-linked lysine fragments, called desmosins and isodesmosins, are formed.

Keratin
Keratin, the structural protein of epithelial cells in the outermost layers of the skin, has been isolated from hair, nails,
hoofs, and feathers. Keratin is completely insoluble in cold or hot water; it is not attacked by proteolytic enzymes
(i.e., enzymes that break apart, or lyse, protein molecules), and therefore cannot replace proteins in the diet. The
 51

great stability of keratin results from the numerous disulfide bonds of cystine. The amino acid composition of
keratin differs from that of collagen. Cystine may account for 24 percent of the total amino acids. The peptide chains
of keratin are arranged in approximately equal amounts of antiparallel and parallel pleated sheets, in which the
peptide chains are linked to each other by hydrogen bonds between the carbonyl and imino groups.

Reduction of the disulfide bonds to sulfhydryl groups results in dissociation of the peptide chains, the molecular
weight of which is 25,000 to 28,000 each. The formation of permanent waves in the beauty treatment of hair is
based on partial reduction of the disulfide bonds of hair keratin by thioglycol, or some other mild reducing agent,
and subsequent oxidation of the sulfhydryl groups (−SH) in the reoriented hair to disulfide bonds (−S−S−) by
exposure to the oxygen of the air.

The length of keratin fibres depends on their water content. They can bind approximately 16 percent of water; this
hydration is accompanied by an increase in the length of the fibres of 10 to 12 percent.

The most thoroughly investigated keratin is hair keratin, particularly that of wool. It consists of a mixture of peptides
with high and low cystine content. When wool is heated in water to about 90° C (190° F), it shrinks irreversibly.
This is attributed to the breakage of hydrogen bonds and other noncovalent bonds; disulfide bonds do not seem to be
affected.

Others
The most thoroughly investigated scleroprotein has been fibroin, the insoluble material of silk. The raw silk
comprising the cocoon of the silkworm consists of two proteins. One, sericin, is soluble in hot water; the other,
fibroin, is not. The amino acid composition of the latter differs from that of all other proteins. It contains large
amounts of glycine, alanine, tyrosine, and serine; small amounts of the other amino acids; and no sulfur-containing
ones. The peptide chains are arranged in antiparallel β-structures. Fibroin is partly soluble in concentrated solutions
of lithium thiocyanate or in mixtures of cupric salts and ethylene diamine. Such solutions contain a protein of
molecular weight 170,000, which is a dimer of two subunits.

Little is known about either the scleroproteins of the marine sponges or the insoluble proteins of the cellular
membranes of animal cells. Some of the membranes are soluble in detergents; others, however, are detergent-
insoluble.

The muscle proteins

The total amount of muscle proteins in mammals, including humans, exceeds that of any other protein. About 40
percent of the body weight of a healthy human adult weighing about 70 kilograms (150 pounds) is muscle, which is
composed of about 20 percent muscle protein. Thus, the human body contains about 5 to 6 kilograms (11 to 13
pounds) of muscle protein. An albumin-like fraction of these proteins, originally called myogen, contains various
enzymes—phosphorylase, aldolase, glyceraldehyde phosphate dehydrogenase, and others; it does not seem to be
involved in contraction. The globulin fraction contains myosin, the contractile protein, which also occurs in blood
platelets, small bodies found in blood. Similar contractile substances occur in other contractile structures; for
example, in the cilia or flagella (whiplike organs of locomotion) of bacteria and protozoans. In contrast to the
scleroproteins, the contractile proteins are soluble in salt solutions and susceptible to enzymatic digestion.

The energy required for muscle contraction is provided by the oxidation of carbohydrates or lipids. The term
mechanochemical reaction has been used for this conversion of chemical into mechanical energy. The molecular
process underlying the reaction is known to involve the fibrous muscle proteins, the peptide chains of which
undergo a change in conformation during contraction.

Myosin, which can be removed from fresh muscle by adding it to a chilled solution of dilute potassium chloride and
sodium bicarbonate, is insoluble in water. Myosin, solutions of which are highly viscous, consists of an elongated—
probably double-stranded—peptide chain, which is coiled at both ends in such a way that a terminal globule is
formed. The length of the molecule is approximately 160 nanometres and its average diameter 2.6 nanometres. The
equivalent weight of each of the two terminal globules is approximately 30,000; the molecular weight of myosin is
close to 500,000. Trypsin splits myosin into large fragments called meromyosin. Myosin contains many amino acids
 52

with positively and negatively charged side chains; they form 18 and 16 percent, respectively, of the total number of
amino acids. Myosin catalyzes the hydrolytic cleavage of ATP (adenosine triphosphate). A smaller protein with
properties similar to those of myosin is tropomyosin. It has a molecular weight of 70,000 and dimensions of 45 by 2
nanometres. More than 90 percent of its peptide chains are present in the α-helix form.

Myosin combines easily with another muscle protein called actin, the molecular weight of which is about 50,000; it
forms 12 to 15 percent of the muscle proteins. Actin can exist in two forms—one, G-actin, is globular; the other, F-
actin, is fibrous. Actomyosin is a complex molecule formed by one molecule of myosin and one or two molecules of
actin. In muscle, actin and myosin filaments are oriented parallel to each other and to the long axis of the muscle.
The actin filaments are linked to each other lengthwise by fine threads called S filaments. During contraction the S
filaments shorten, so that the actin filaments slide toward each other, past the myosin filaments, thus causing a
shortening of the muscle (for a detailed description of the process, see muscle: Striated muscle).

Fibrinogen and fibrin

Fibrinogen, the protein of the blood plasma, is converted into the insoluble protein fibrin during the clotting process.
The fibrinogen-free fluid obtained after removal of the clot, called blood serum, is blood plasma minus fibrinogen.
The fibrinogen content of the blood plasma is 0.2 to 0.4 percent.

Fibrinogen can be precipitated from the blood plasma by half-saturation with sodium chloride. Fibrinogen solutions
are highly viscous and show strong flow birefringence. In electron micrographs the molecules appear as rods with a
length of 47.5 nanometres and a diameter of 1.5 nanometres; in addition, two terminal and a central nodule are
visible. The molecular weight is 340,000. An unusually high percentage, about 36 percent, of the amino acid side
chains are positively or negatively charged.

The clotting process is initiated by the enzyme thrombin, which catalyzes the breakage of a few peptide bonds of
fibrinogen; as a result, two small fibrinopeptides with molecular weights of 1,900 and 2,400 are released. The
remainder of the fibrinogen molecule, a monomer, is soluble and stable at pH values less than 6 (i.e., in acid
solutions). In neutral solution (pH 7) the monomer is converted into a larger molecule, insoluble fibrin; this results
from the formation of new peptide bonds. The newly formed peptide bonds form intermolecular and intramolecular
cross links, thus giving rise to a large clot, in which all molecules are linked to each other. Clotting, which takes
place only in the presence of calcium ions, can be prevented by compounds such as oxalate or citrate, which have a
high affinity for calcium ions.

Albumins, globulins, and other soluble proteins

The blood plasma, the lymph, and other animal fluids usually contain one to seven grams of protein per 100
millilitres of fluid, which includes small amounts of hundreds of enzymes and a large number of protein hormones.
The discussion below is limited largely to the proteins that occur in large amounts and can be easily isolated from
the body fluids.

Proteins of the blood serum

Human blood serum contains about 7 percent protein, two-thirds of which is in the albumin fraction; the other third
is in the globulin fraction. Electrophoresis of serum reveals a large albumin peak and three smaller globulin peaks,
the alpha-, beta-, and gamma-globulins. The amounts of alpha-, beta-, and gamma-globulin in normal human serum
are approximately 1.5, 1.9, and 1.1 percent, respectively. Each globulin fraction is a mixture of many different
proteins, as has been demonstrated by immunoelectrophoresis. In this method, serum from an animal (e.g., a rabbit)
injected with human serum is allowed to diffuse into the four protein bands—albumin, alpha-, beta-, and gamma-
globulin—obtained from the electrophoresis of human serum. Because the animal has previously been injected with
human serum, its blood contains antibodies (substances formed in response to a foreign substance introduced into
the body) against each of the human serum proteins; each antibody combines with the serum protein (antigen) that
 53

caused its formation in the animal. The result is the formation of about 20 regions of insoluble antigen-antibody
precipitate, which appear as white arcs in the transparent gel of the electrophoresis medium. Each region
corresponds to a different human serum protein.

Serum albumin is much less heterogeneous (i.e., contains fewer distinct proteins) than are the globulins; in fact, it is
one of the few serum proteins that can be obtained in a crystalline form. Serum albumin combines easily with many
acidic dyes (e.g., Congo red and methyl orange); with bilirubin, the yellow bile pigment; and with fatty acids. It
seems to act, in living organisms, as a carrier for certain biological substances. Present in blood serum in relatively
high concentration, serum albumin also acts as a protective colloid, a protein that stabilizes other proteins. Albumin
(molecular weight of 68,000) has a single free sulfhydryl (−SH) group, which on oxidation forms a disulfide bond
with the sulfhydryl group of another serum albumin molecule, thus forming a dimer. The isoelectric point of serum
albumin is pH 4.7.

The alpha-globulin fraction of blood serum is a mixture of several conjugated proteins. The best known are an α-
lipoprotein (combination of lipid and protein) and two mucoproteins (combinations of carbohydrate and protein).
One mucoprotein is called orosomucoid, or α1-acid glycoprotein; the other is called haptoglobin because it combines
specifically with globin, the protein component of hemoglobin. Haptoglobin contains about 20 percent carbohydrate.
The beta-globulin fraction of serum contains, in addition to lipoproteins and mucoproteins, two metal-binding
proteins, transferrin and ceruloplasmin, which bind iron and copper, respectively. They are the principal iron and
copper carriers of the blood.

The gamma-globulins are the most heterogeneous globulins. Although most have a molecular weight of
approximately 150,000, that of some, called macroglobulins, is as high as 800,000. Because typical antibodies are of
the same size and exhibit the same electrophoretic behaviour as γ-globulins, they are called immunoglobulins. The
designation IgM or gamma M (γM) is used for the macroglobulins; the designation IgG or gamma G (γG) is used
for γ−globulins of molecular weight 150,000.

Milk proteins
Milk contains the following: an albumin, α-lactalbumin; a globulin, beta-lactoglobulin; and a phosphoprotein,
casein. If acid is added to milk, casein precipitates. The remaining watery liquid (the supernatant solution), or whey,
contains α-lactalbumin and β-lactoglobulin. Both have been obtained in crystalline form; in bovine milk, their
molecular weights are approximately 14,000 and 18,400, respectively. Lactoglobulin also occurs as a dimer of
molecular weight 37,000. Genetic variations can produce small variations in the amino acid composition of
lactoglobulin. The amino acid composition and the tertiary structure of lactalbumin resemble that of lysozyme, an
egg protein.

Casein is precipitated not only by the addition of acid but also by the action of the enzyme rennin, which is found in
gastric juice. Rennin from calf stomachs is used to precipitate casein, from which cheese is made. Milk fat
precipitates with casein; milk sugar, however, remains in the supernatant (whey). Casein is a mixture of several
similar phosphoproteins, called α-, β-, γ−, and κ-casein, all of which contain some serine side chains combined with
phosphoric acid. Approximately 75 percent of casein is α-casein. Cystine has been found only in κ-casein. In milk,
casein seems to form polymeric globules (micelles) with radially arranged monomers, each with a molecular weight
of 24,000; the acidic side chains occur predominantly on the surface of the micelle, rather than inside.

Egg proteins
About 50 percent of the proteins of egg white are composed of ovalbumin, which is easily obtained in crystals. Its
molecular weight is 46,000 and its amino acid composition differs from that of serum albumin. Other proteins of egg
white are conalbumin, lysozyme, ovoglobulin, ovomucoid, and avidin. Lysozyme is an enzyme that hydrolyzes the
carbohydrates found in the capsules certain bacteria secrete around themselves; it causes lysis (disintegration) of the
bacteria. The molecular weight of lysozyme is 14,100. Its three-dimensional structure is similar to that of α-
lactalbumin, which stimulates the formation of lactose by the enzyme lactose synthetase. Lysozyme has also been
found in the urine of patients suffering from leukemia, meningitis, and renal disease.
 54

Avidin is a glycoprotein that combines specifically with biotin, a vitamin. In animals fed large amounts of raw egg
white, the action of avidin results in “egg-white injury.” The molecular weight of avidin, which forms a tetramer, is
16,200. Its amino acid sequence is known.

Egg-yolk proteins contain a mixture of lipoproteins and livetins. The latter are similar to serum albumin, α-globulin,
and β-globulin. The yolk also contains a phosphoprotein, phosvitin. Phosvitin, which has also been found in fish
sperm, has a molecular weight of 40,000 and an unusual amino acid composition; one third of its amino acids are
phosphoserine.

Protamines and histones

Protamines are found in the sperm cells of fish. The most thoroughly investigated protamines are salmine from
salmon sperm and clupeine from herring sperm. The protamines are bound to deoxyribonucleic acid (DNA),
forming nucleoprotamines. The amino acid composition of the protamines is simple; they contain, in addition to
large amounts of arginine, small amounts of five or six other amino acids. The composition of the salmine molecule,
for example, is: Arg51, Ala4, Val4, Ile1, Pro7, and Ser6, in which the subscript numbers indicate the number of each
amino acid in the molecule. Because of the high arginine content, the isoelectric points of the protamines are at pH
values of 11 to 12; i.e., the protamines are alkaline. The molecular weights of salmine and clupeine are close to
6,000. All of the protamines investigated thus far are mixtures of several similar proteins.

The histones are less basic than the protamines. They contain high amounts of either lysine or arginine and small
amounts of aspartic acid and glutamic acid. Histones occur in combination with DNA as nucleohistones in the nuclei
of the body cells of animals and plants, but not in animal sperm. The molecular weights of histones vary from
10,000 to 22,000. In contrast to the protamines, the histones contain most of the 20 amino acids, with the exception
of tryptophan and the sulfur-containing ones. Like the protamines, histone preparations are heterogeneous mixtures.
The amino acid sequence of some of the histones has been determined.

Plant proteins
Plant proteins, mostly globulins, have been obtained chiefly from the protein-rich seeds of cereals and legumes.
Small amounts of albumins are found in seeds. The best known globulins, insoluble in water, can be extracted from
seeds by treatment with 2 to 10 percent solutions of sodium chloride. Many plant globulins have been obtained in
crystalline form; they include edestin from hemp, molecular weight 310,000; amandin from almonds, 330,000;
concanavalin A (42,000) and B (96,000); and canavalin (113,000) from jack beans. They are polymers of smaller
subunits; edestin, for example, is a hexamer of a subunit with a molecular weight of 50,000, and concanavalin B a
trimer of a subunit with a molecular weight of 30,000. After extraction of lipids from cereal seeds by ether and
alcohol, further extraction with water containing 50 to 80 percent of alcohol yields proteins that are insoluble in
water but soluble in water–ethanol mixtures and have been called prolamins. Their solubility in aqueous ethanol
may result from their high proline and glutamine content. Gliadin, the prolamin from wheat, contains 14 grams of
proline and 46 grams of glutamic acid in 100 grams of protein; most of the glutamic acid is in the form of glutamine.
The total amounts of the basic amino acids (arginine, lysine, and histidine) in gliadin are only 5 percent of the
weight of gliadin. Because the glysine content is either low or nonexistent, human populations dependent on grain as
a sole protein source suffer from lysine deficiency.

Conjugated proteins
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Combination of proteins with prosthetic groups

The link between a protein molecule and its prosthetic group is a covalent bond (an electron-sharing bond) in the
glycoproteins, the biliproteins, and some of the heme proteins. In lipoproteins, nucleoproteins, and some heme
 55

proteins, the two components are linked by noncovalent bonds; the bonding results from the same forces that are
responsible for the tertiary structure of proteins: hydrogen bonds, salt bridges between positively and negatively
charged groups, disulfide bonds, and mutual interaction of hydrophobic groups. In the metalloproteins (proteins with
a metal element as a prosthetic group), the metal ion usually forms a centre to which various groups are bound.

Some of the conjugated proteins have been mentioned in preceding sections because they occur in the blood serum,
in milk, and in eggs; others are discussed below in sections dealing with respiratory proteins and enzymes.

Mucoproteins and glycoproteins

The prosthetic groups in mucoproteins and glycoproteins are oligosaccharides (carbohydrates consisting of a small
number of simple sugar molecules) usually containing from four to 12 sugar molecules; the most common sugars are
galactose, mannose, glucosamine, and galactosamine. Xylose, fucose, glucuronic acid, sialic acid, and other simple
sugars sometimes also occur. Some mucoproteins contain 20 percent or more of carbohydrate, usually in several
oligosaccharides attached to different parts of the peptide chain. The designation mucoprotein is used for proteins
with more than 3 to 4 percent carbohydrate; if the carbohydrate content is less than 3 percent, the protein is
sometimes called a glycoprotein or simply a protein.

Mucoproteins, highly viscous proteins originally called mucins, are found in saliva, in gastric juice, and in other
animal secretions. Mucoproteins occur in large amounts in cartilage, synovial fluid (the lubricating fluid of joints
and tendons), and egg white. The mucoprotein of cartilage is formed by the combination of collagen with
chondroitinsulfuric acid, which is a polymer of either glucuronic or iduronic acid and acetylhexosamine or
acetylgalactosamine. It is not yet clear whether or not chondroitinsulfate is bound to collagen by covalent bonds.

Lipoproteins and proteolipids

The bond between the protein and the lipid portion of lipoproteins and proteolipids is a noncovalent one. It is
thought that some of the lipid is enclosed in a meshlike arrangement of peptide chains and becomes accessible for
reaction only after the unfolding of the chains by denaturing agents. Although lipoproteins in the α- and β-globulin
fraction of blood serum are soluble in water (but insoluble in organic solvents), some of the brain lipoproteins,
because they have a high lipid content, are soluble in organic solvents; they are called proteolipids. The β-
lipoprotein of human blood serum is a macroglobulin with a molecular weight of about 1,300,000, 70 percent of
which is lipid; of the lipid, about 30 percent is phospholipid and 40 percent cholesterol and compounds derived from
it. Because of their lipid content, the lipoproteins have the lowest density (mass per unit volume) of all proteins and
are usually classified as low- and high-density lipoproteins (LDL and HDL).

Coloured lipoproteins are formed by the combination of protein with carotenoids. Crustacyanin, the pigment of
lobsters, crayfish, and other crustaceans, contains astaxanthin, which is a compound derived from carotene. Among
the most interesting of the coloured lipoproteins are the pigments of the retina of the eye. They contain retinal,
which is a compound derived from carotene and which is formed by the oxidation of vitamin A. In rhodopsin, the
red pigment of the retina, the aldehyde group (−CHO) of retinal forms a covalent bond with an amino (−NH2) group
of opsin, the protein carrier. Colour vision is mediated by the presence of several visual pigments in the retina that
differ from rhodopsin either in the structure of retinal or in that of the protein carrier.

Metalloproteins
Proteins in which heavy metal ions are bound directly to some of the side chains of histidine, cysteine, or some other
amino acid are called metalloproteins. Two metalloproteins, transferrin and ceruloplasmin, occur in the globulin
fractions of blood serum; they act as carriers of iron and copper, respectively. Transferrin has a molecular weight of
about 80,000 and consists of two identical subunits, each of which contains one ferric ion (Fe3+) that seems to be
bound to tyrosine. Several genetic variants of transferrin are known to occur in humans. Another iron protein,
ferritin, which contains 20 to 22 percent iron, is the form in which iron is stored in animals; it has been obtained in
crystalline form from liver and spleen. A molecule consisting of 20 subunits, its molecular weight is approximately
480,000. The iron can be removed by reduction from the ferric (Fe3+) to the ferrous (Fe2+) state. The iron-free
protein, apoferritin, is synthesized in the body before the iron is incorporated.
 56

Green plants and some photosynthetic and nitrogen-fixing bacteria (i.e., bacteria that convert atmospheric nitrogen,
N2, into amino acids and proteins) contain various ferredoxins. They are small proteins containing 50 to 100 amino
acids and a chain of iron and disulfide units (FeS2), in which some of the sulfur atoms are contributed by cysteine;
others are sulfide ions (S2−). The number of FeS2 units per ferredoxin molecule varies from five in the ferredoxin of
spinach to 10 in the ferredoxin of certain bacteria. Ferredoxins act as electron carriers in photosynthesis and in
nitrogen fixation.

Ceruloplasmin is a copper-containing globulin that has a molecular weight of 151,000; the molecule consists of
eight subunits, each containing one copper ion. Ceruloplasmin is the principal carrier of copper in organisms,
although copper can also be transported by the iron-containing globulin transferrin. Another copper-containing
protein, copper-zinc superoxide dismutase (formerly known as erythrocuprein), has been isolated from red blood
cells; it has also been found in the liver and in the brain. The molecule, which consists of two subunits of similar
size, contains copper ions and zinc ions. Because of their copper content, ceruloplasmin and copper-zinc superoxide
dismutase possess catalytic activity in oxidation-reduction reactions.

Many animal enzymes contain zinc ions, which are usually bound to the sulfur of cysteine. Horse kidneys contain
the protein metallothionein, which contain zinc and cadmium; both are bound to sulfur. A vanadium-protein
complex (hemovanadin) has been found in surprisingly high amounts in yellowish-green cells (vanadocytes) of
tunicates, which are marine invertebrates.

Heme proteins and other chromoproteins

Although the heme proteins contain iron, they are usually not classified as metalloproteins, because their prosthetic
group is an iron-porphyrin complex in which the iron is bound very firmly. The intense red or brown colour of the
heme proteins is not caused by iron but by porphyrin, a complex cyclic structure. All porphyrin compounds absorb
light intensely at or close to 410 nanometres. Porphyrin consists of four pyrrole rings (five-membered closed
structures containing one nitrogen and four carbon atoms) linked to each other by methine groups (−CH=). The iron
atom is kept in the centre of the porphyrin ring by interaction with the four nitrogen atoms. The iron atom can
combine with two other substituents; in oxyhemoglobin, one substituent is a histidine of the protein carrier, the other
is an oxygen molecule. In some heme proteins, the protein is also bound covalently to the side chains of porphyrin.
Heme proteins are described below (see Respiratory proteins).

The chromoprotein melanin, a pigment found in dark skin, dark hair, and melanotic tumours, occurs in every major
group of living organisms and appears to be remarkably diverse in structure. In humans, melanin produced by
melanocytes may be dark brown (eumelanin) or pale red or yellowish (phaeomelanin). The different types are
synthesized via different pathways, though they share the same initial step—the oxidation of tyrosine.

Green chromoproteins called biliproteins are found in many insects, such as grasshoppers, and also in the eggshells
of many birds. The biliproteins are derived from the bile pigment biliverdin, which in turn is formed from porphyrin;
biliverdin contains four pyrrole rings and three of the four methine groups of porphyrin. Large amounts of
biliproteins have been found in red algae and blue-green algae; the red protein is called phycoerythrin, the blue one
phycocyanobilin.

•
Blue-green algae in Morning Glory Pool, Yellowstone National Park, Wyoming.

© Yoyo_slc/Shutterstock.com

Nucleoproteins
When a protein solution is mixed with a solution of a nucleic acid, the phosphoric acid component of the nucleic
acid combines with the positively charged ammonium groups (−NH3+) of the protein to form a protein–nucleic acid
complex. The nucleus of a cell contains predominantly deoxyribonucleic acid (DNA) and the cytoplasm
 57

predominantly ribonucleic acid (RNA); both parts of the cell also contain protein. Protein–nucleic acid complexes,
therefore, form in living cells.

The only nucleoproteins for which some evidence for specificity exists are nucleoprotamines, nucleohistones, and
some RNA and DNA viruses. The nucleoprotamines are the form in which protamines occur in the sperm cells of
fish; the histones of the thymus and of pea seedlings and other plant material apparently occur predominantly as
nucleohistones. Both nucleoprotamines and nucleohistones contain only DNA.

Some of the simplest viruses consist of a specific RNA, which is coated by protein. One of the best known RNA
viruses, tobacco mosaic virus (TMV), has the shape of a rod. RNA comprises only 5.1 percent of the mass of the
virus. The complete sequence of the virus protein, which consists of about 2,130 identical peptide chains, each
containing 158 amino acids, has been determined. The protein is arranged in a spiral around the RNA core.

•
Schematic structure of the tobacco mosaic virus. The cutaway section shows the helical ribonucleic …

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DNA has been found in most bacterial viruses (bacteriophages) and in some animal viruses. As in TMV, the core of
DNA is surrounded by protein. Phage protein is a mixture of enzymes and therefore cannot be considered as the
protein portion of only one nucleoprotein.

Respiratory proteins

Hemoglobin
Hemoglobin is the oxygen carrier in all vertebrates and some invertebrates. In oxyhemoglobin (HbO2), which is
bright red, the ferrous ion (Fe2+) is bound to the four nitrogen atoms of porphyrin; the other two substituents are an
oxygen molecule and the histidine of globin, the protein component of hemoglobin. Deoxyhemoglobin (deoxy-Hb),
as its name implies, is oxyhemoglobin minus oxygen (i.e., reduced hemoglobin); it is purple in colour. Oxidation of
the ferrous ion of hemoglobin yields a ferric compound, methemoglobin, sometimes called hemiglobin or
ferrihemoglobin. The oxygen of oxyhemoglobin can be displaced by carbon monoxide, for which hemoglobin has a
much greater affinity, preventing oxygen from reaching the body tissues.

•
Hemoglobin is a protein made up of four polypeptide chains (α1, …

Encyclopædia Britannica, Inc.

The hemoglobins of all mammals, birds, and many other vertebrates are tetramers of two α- and two β-chains. The
molecular weight of the tetramer is 64,500; the molecular weight of the α- and β-chains is approximately 16,100
each, and the four subunits are linked to each other by noncovalent interactions. If hemin (the ferric porphyrin
component) is removed from globin (the protein component), two molecules of globin, each consisting of one α-
and one β-chain, are obtained; the molecular weight of globin is 32,200. In contrast to hemoglobin, globin is an
unstable protein that is easily denatured. If native globin is incubated with a solution of hemin at pH values of 8 to 9,
native hemoglobin is reconstituted. Myoglobin, the red pigment of mammalian muscles, is a monomer with a
molecular weight of 16,000.

The mammalian hemoglobins differ from each other in their amino acid composition and therefore in their
secondary and tertiary structure. Rat and horse hemoglobins crystallize very easily, but those of humans, cattle, and
sheep, because they are more soluble, are difficult to crystallize. The shape of hemoglobin crystals varies in different
species; moreover, decomposition and denaturation occur at different rates in different species. It was also found
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that the blood of human newborns contains two different hemoglobins: about 20 percent of their hemoglobin is an
adult hemoglobin (hemoglobin A) and 80 percent is a fetal hemoglobin (hemoglobin F). Hemoglobin F persists in
the infant for the first seven months of life. The same hemoglobin F has also been found in the blood of patients
suffering from thalassemia, an anemia with a high incidence in regions surrounding the Mediterranean Sea.
Hemoglobin F contains, as does hemoglobin A, two α-chains; the two β-chains, however, have been replaced by
two quite different γ-chains. When the technique of electrophoresis was first applied to the hemoglobin of blacks
suffering from sickle cell anemia in 1949, a new hemoglobin (hemoglobin S) was discovered. More than 200
different human hemoglobins have been discovered since. They differ from normal hemoglobin A in the amino acid
composition of either the α- or the β-chain.

The hemoglobins of some of the lowest fishes are monomers containing one iron atom per molecule. Hemoglobin-
like respiratory proteins have been found in some invertebrates. The red hemoglobin of insects, mollusks, and
protozoans is called erythrocruorin. It differs from vertebrate hemoglobin by its high molecular weight.

Although green plants contain no hemoglobin, a red protein, called leghemoglobin, has been discovered in the root
nodules of leguminous plants. It seems to be produced by the nitrogen-fixing bacteria of the root nodules and may
be involved in the reduction of atmospheric nitrogen to ammonia and amino acids.

Other respiratory proteins

A green respiratory protein, chlorocruorin, has been found in the blood of marine worms in the genera Serpula and
Spirographis. It has the same high molecular weight as erythrocruorin but differs from hemoglobin in its prosthetic
group. A red metalloprotein, hemerythrin, acts as a respiratory protein in marine worms of the phylum Sipuncula.
The molecule consists of eight subunits with a molecular weight of 13,500 each. Hemerythrin contains no
porphyrins and therefore is not a heme protein.

A metalloprotein containing copper is the respiratory protein of crustaceans (shrimps, crabs, etc.) and of some
gastropods (snails). The protein, called hemocyanin, is pale yellow when not combined with oxygen, and blue when
combined with oxygen. The molecular weights of hemocyanins vary from 300,000 to 9,000,000. Each animal
investigated thus far apparently has a species-specific hemocyanin.

Protein hormones
Some hormones that are products of endocrine glands are proteins or peptides, others are steroids. (The origin of
hormones, their physiological role, and their mode of action are dealt with in the article hormone.) None of the
hormones has any enzymatic activity. Each has a target organ in which it elicits some biological action—e.g.,
secretion of gastric or pancreatic juice, production of milk, production of steroid hormones. The mechanism by
which the hormones exert their effects is not fully understood. Cyclic adenosine monophosphate is involved in the
transmittance of the hormonal stimulus to the cells whose activity is specifically increased by the hormone.

Hormones of the thyroid gland

Thyroglobulin, the active groups of which are two molecules of the iodine-containing compound thyroxine, has a
molecular weight of 670,000. Thyroglobulin also contains thyroxine with two and three iodine atoms instead of four
and tyrosine with one and two iodine atoms. Injection of the hormone causes an increase in metabolism; lack of it
results in a slowdown.

Another hormone, calcitonin, which lowers the calcium level of the blood, occurs in the thyroid gland. The amino
acid sequences of calcitonin from pig, beef, and salmon differ from human calcitonin in some amino acids. All of
them, however, have the half-cystines (C) and the prolinamide (P) in the same position.

Parathyroid hormone (parathormone), produced in small glands that are embedded in or lie behind the thyroid gland,
is essential for maintaining the calcium level of the blood. A decrease in its production results in hypocalcemia (a
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reduction of calcium levels in the bloodstream below the normal range). Bovine parathormone has a molecular
weight of 8,500; it contains no cystine or cysteine and is rich in aspartic acid, glutamic acid, or their amides.

Hormones of the pancreas

Although the amino acid structure of insulin has been known since 1949, repeated attempts to synthesize it gave
very poor yields because of the failure of the two peptide chains to combine forming the correct disulfide bridge.
The ease of the biosynthesis of insulin is explained by the discovery in the pancreas of proinsulin, from which
insulin is formed. The single peptide chain of proinsulin loses a peptide consisting of 33 amino acids and called the
connecting peptide, or C peptide, during its conversion to insulin. The disulfide bridges of proinsulin connect the A
and B chains.

In aqueous solutions, insulin exists predominantly as a complex of six subunits, each of which contains an A and a B
chain. The insulins of several species have been isolated and analyzed; their amino acid sequences have been found
to differ somewhat, but all apparently contain the same disulfide bridges between the two chains.

Although the injection of insulin lowers the blood sugar, administration of glucagon, another pancreas hormone,
raises the blood sugar level. Glucagon consists of a straight peptide chain of 29 amino acids. It has been synthesized;
the synthetic product has the full biological activity of natural glucagon. The structure of glucagon is free of cystine
and isoleucine.

The pituitary gland has an anterior lobe, a posterior lobe, and an intermediate portion; they differ in cellular structure
and in the structure and action of the hormones they form. The posterior lobe produces two similar hormones,
oxytocin and vasopressin. The former causes contraction of the pregnant uterus; the latter raises the blood pressure.
Both are octapeptides formed by a ring of five amino acids (the two cystine halves count as one amino acid) and a
side chain of three amino acids. The two cystine halves are linked to each other by a disulfide bond, and the C
terminal amino acid is glycinamide. The structure has been established and confirmed. Human vasopressin differs
from oxytocin in that isoleucine is replaced by phenylalanine and leucine by arginine.

The intermediate part of the pituitary gland produces the melanocyte-stimulating hormone (MSH), which causes
expansion of the pigmented melanophores (cells) in the skin of frogs and other batrachians. Two hormones, called
α-MSH and β-MSH, have been prepared from hog pituitary glands. The first, α-MSH, consists of 13 amino acids;
its N terminal serine is acetylated (i.e., the acetyl group, CH3CO, of acetic acid is attached), and its C terminal valine
residue is present as valinamide. The second, β-MSH, contains in its 18 amino acids many of those occurring in α-
MSH.

The anterior pituitary lobe produces several protein hormones—a thyroid-stimulating hormone (thyrotropin),
molecular weight 28,000; a lactogenic hormone, molecular weight 22,500; a growth hormone, molecular weight
21,500; a luteinizing hormone, molecular weight 30,000; and a follicle-stimulating hormone, molecular weight
29,000. The thyroid-stimulating hormone consists of α and β subunits with a composition similar to the subunits of
luteinizing hormone. When separated, neither of the two subunits has hormonal activity; when combined, however,
they regain about 50 percent of the original activity. The lactogenic hormone (prolactin) from sheep pituitary glands
contains 190 amino acids. Their sequence has been elucidated; a similar peptide chain of 188 amino acids that has
been synthesized not only has 10 percent of the biological activity of the natural hormone but also some activity of
the growth hormone. The amino acid sequence of the growth hormone (somatotropic hormone) is also known; it
seems to stimulate the synthesis of RNA and in this way to accelerate growth. The luteinizing hormone, a
mucoprotein containing about 12 percent carbohydrate, consists of two subunits, each with a molecular weight of
approximately 15,000; when separated, the subunits recombine spontaneously. The urine of pregnant women
contains chorionic gonadotropin, the presence of which makes possible early diagnosis of pregnancy. The amino
acid sequence is known. The sequence of 160 of its 190 amino acids is identical with those of the growth hormone;
 60

100 of these also occur in the same sequence as in lactogenic hormone. The different pituitary hormones and the
chorionic gonadotropin thus may have been derived from a common substance that, during evolution, underwent
differentiation.

Peptides with hormonelike activity

Small peptides have been discovered that, like hormones, act on certain target organs. One peptide, angiotensin
(angiotonin or hypertensin), is formed in the blood from angiotensinogen by the action of renin, an enzyme of the
kidney. It is an octapeptide and increases blood pressure. Similar peptides include bradykinin, which stimulates
smooth muscles; gastrin, which stimulates secretion of hydrochloric acid and pepsin in the stomach; secretin, which
stimulates the flow of pancreatic juice; and kallikrein, the activity of which is similar to bradykinin.

Immunoglobulins and antibodies

Antibodies, proteins that combat foreign substances in the body, are associated with the globulin fraction of the
immune serum. As stated previously, when the serum globulins are separated into α-, β-, and γ- fractions, antibodies
are associated with the γ-globulins. Antibodies can be purified by precipitation with the antigen (i.e., the foreign
substance) that caused their formation, followed by separation of the antigen-antibody complex. Antibodies prepared
in this way consist of a mixture of many similar antibody molecules, which differ in molecular weight, amino acid
composition, and other properties. The same differences are found in the γ-globulins of normal blood serums. The γ-
globulin of normal blood serum is thought to consist of a mixture of hundreds of different γ-globulins, each of
which occurs in amounts too small for isolation. Because the physical and chemical properties of normal γ-globulins
are the same as those of antibodies, the γ-globulins are frequently called immunoglobulins. They may be considered
to be antibodies against unknown antigens. If solutions of γ-globulin are resolved by gel filtration through dextran,
the first fraction has a molecular weight of 900,000. This fraction is called IgM or γM; Ig is an abbreviation for
immunoglobulin and M for macroglobulin. The next two fractions are IgA (γA) and IgG (γG), with molecular
weights of about 320,000 and 150,000 respectively. Two other immunoglobulins, known as IgD and IgE, have also
been detected in much smaller amounts in some immune sera.

The bulk of the immunoglobulins is found in the IgG fraction, which also contains most of the antibodies. The IgM
molecules are apparently pentamers—aggregates of five of the IgG molecules. Electron microscopy shows their five
subunits to be linked to each other by disulfide bonds in the form of a pentagon. The IgA molecules are found
principally in milk and in secretions of the intestinal mucosa. Some of them contain, in addition to a dimer of IgG, a
“secretory piece” that enables the passage of IgA molecules between tissue and fluid; the structure of the secretory
piece is not yet known. The IgM and IgA immunoglobulins and antibodies contain 10 to 15 percent carbohydrate;
the carbohydrate content of the IgG molecules is 2 to 3 percent.

IgG molecules treated with the enzyme papain split into three fragments of almost identical molecular weight of
50,000. Two of these, called Fab fragments, are identical; the third is abbreviated Fc. Reduction to sulfhydryl groups
of some of the disulfide bonds of IgG results in the formation of two heavy, or H, chains (molecular weight 55,000)
and two light, or L, chains (molecular weight 22,000). They are linked by disulfide bonds in the order L−H−H−L.
Each H chain contains four intrachain disulfide bonds, and each L chain contains two.

Antibody preparations of the IgG type, even after removal of IgM and IgA antibodies, are heterogeneous. The H and
L chains consist of a large number of different L chains and a variety of H chains. Pure IgG, IgM, and IgA
immunoglobulins, however, occur in the blood serum of patients suffering from myelomas, which are malignant
tumours of the bone marrow. The tumours produce either an IgG, an IgM, or an IgA protein, but rarely more than
one class. A protein called the Bence-Jones protein, which is found in the urine of patients suffering from myeloma
tumours, is identical with the L chains of the myeloma protein. Each patient has a different Bence-Jones protein; no
two of the more than 100 Bence-Jones proteins that have been analyzed thus far are identical. It is thought that one
lymphoid cell among hundreds of thousands becomes malignant and multiplies rapidly, forming the mass of a
myeloma tumour that produces one γ-globulin.
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Analyses of the Bence-Jones proteins have revealed that the L chains of humans and other mammals are of two quite
different types, kappa (κ) and lambda (λ). Both consist of approximately 220 amino acids. The N–terminal halves of
κ- and λ-chains are variable, differing in each Bence-Jones protein. The C–terminal halves of these same L chains
have a constant amino acid sequence of either the κ- or the λ-type. The fact that one half of a peptide chain is
variable and the other half invariant is contradictory to the view that the amino acid sequence of each peptide chain
is determined by one gene. Evidently, two genes, one of them variable, the other invariant, fuse to form the gene for
the single peptide chain of the L chains. Whereas the normal human L chains are always mixtures of the κ- and λ-
types, the H chains of IgG, IgM, and IgA are different. They have been designated as gamma (γ), mu (μ), and alpha
(α) chains, respectively. The N-terminal quarter of the H chains has a variable amino acid sequence; the C-terminal
three-quarters of the H chains have a constant amino acid sequence.

Some of the amino acid sequences in the L and H chains are transmitted from generation to generation. As a result,
the constant portion of the human L chains of the κ-type has in position 191 either valine or leucine. They
correspond to two alleles (character-determining portions) of a gene; the two types are called allotypes. The valine-
containing genetic type has been designated as InV(a+), the leucine-containing type as InV(b+). Many more
allotypes, called Gm allotypes, have been found in the gamma chains of the human IgG immunoglobulins; more
than 20 Gm allotypes are known. Certain combinations of Gm types occur. For example, the combination of Gm
types 5, 6, and 11 has been found in Caucasians and African Americans but not in Chinese; the combination of 1, 2,
and 17 has not been found in African Americans; and the combination of 1, 4, and 17 has not been found in
Caucasians. Allotypes have also been discovered to occur in a number of other animals, including rabbits and mice.

It is understandable from the occurrence of a large number of allotypes that antibodies, even if produced in response
to a single antigen, are mixtures of different allotypes. The existence of several classes of antibodies, of different
allotypes, and of adaptation of the variable portions of antibodies to different regions of an antigen molecule results
in a multiplicity of antibody molecules even if only a single antigen is administered. For this reason it has not yet
been possible to unravel the amino acid sequence in the variable portion of antibody molecules. Much of the amino
acid sequence in the constant regions of the L and H chains of humans and rabbit immunoglobulins, however, has
been resolved.

Enzymes
Practically all of the numerous and complex biochemical reactions that take place in animals, plants, and
microorganisms are regulated by enzymes. These catalytic proteins are efficient and specific—that is, they
accelerate the rate of one kind of chemical reaction of one type of compound, and they do so in a far more efficient
manner than human-made catalysts. They are controlled by activators and inhibitors that initiate or block reactions.
All cells contain enzymes, which usually vary in number and composition, depending on the cell type; an average
mammalian cell, for example, is approximately one one-billionth (10−9) the size of a drop of water and generally
contains about 3,000 enzymes.

The existence of enzymes was established in the middle of the 19th century by scientists studying the process of
fermentation. The discovery of the role of enzymes as catalysts followed rapidly. Developments before 1850
included (in 1833) the separation from malt of the enzyme amylase, which converts starch into sugar, and (in 1836)
the isolation from the stomach wall of animals of a component of gastric juice that could partially digest food in a
test tube, the enzyme pepsin.

Enzymes were known for many years as ferments, a term derived from the Latin word for yeast. In 1878 the name
enzyme, from the Greek words meaning “in yeast,” was introduced; since the late 19th century it has been employed
universally.
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Role of enzymes in metabolism

Some enzymes help to break down large nutrient molecules, such as proteins, fats, and carbohydrates, into smaller
molecules. This process occurs during the digestion of foodstuffs in the stomach and intestines of animals. Other
enzymes guide the smaller, broken-down molecules through the intestinal wall into the bloodstream. Still other
enzymes promote the formation of large, complex molecules from the small, simple ones to produce cellular
constituents. Enzymes are also responsible for numerous other functions, which include the storage and release of
energy, the course of reproduction, the processes of respiration, and vision. They are indispensable to life.

Each enzyme is able to promote only one type of chemical reaction. The compounds on which the enzyme acts are
called substrates. Enzymes operate in tightly organized metabolic systems called pathways. A seemingly simple
biological phenomenon—the contraction of a muscle, for example, or the transmission of a nerve impulse—actually
involves a large number of chemical steps in which one or more chemical compounds (substrates) are converted to
substances called products; the product of one step in a metabolic pathway serves as the substrate for the succeeding
step in the pathway.

The role of enzymes in metabolic pathways can be illustrated diagrammatically. The chemical compound
represented by A (see diagram below) is converted to product E in a series of enzyme-catalyzed steps, in which
intermediate compounds represented by B, C, and D are formed in succession. They act as substrates for enzymes
represented by 2, 3, and 4. Compound A may also be converted by another series of steps, some of which are the
same as those in the pathway for the formation of E, to products represented by G and H.

The letters represent chemical compounds; numbers represent enzymes that catalyze individual reactions. The
relative heights represent the thermodynamic energy of the compounds (e.g., compound A is more energy-rich than
B, B more energy-rich than C). Compounds A, B, etc., change very slowly in the absence of a catalyst but do so
rapidly in the presence of catalysts 1, 2, 3, etc.

The regulatory role of enzymes in metabolic pathways can be clarified by using a simple analogy: that between the
compounds, represented by letters in the diagram, and a series of connected water reservoirs on a slope. Similarly,
the enzymes represented by the numbers are analogous to the valves of the reservoir system. The valves control the
flow of water in the reservoir; that is, if only valves 1, 2, 3, and 4 are open, the water in A flows only to E, but, if
valves 1, 2, 5, and 6 are open, the water in A flows to G. In a similar manner, if enzymes 1, 2, 3, and 4 in the
metabolic pathway are active, product E is formed, and, if enzymes 1, 2, 5, and 6 are active, product G is formed.
The activity or lack of activity of the enzymes in the pathway therefore determines the fate of compound A; i.e., it
either remains unchanged or is converted to one or more products. In addition, if products are formed, the activity of
enzymes 3 and 4 relative to that of enzymes 5 and 6 determines the quantity of product E formed compared with
product G.

Both the flow of water and the activity of enzymes obey the laws of thermodynamics; hence, water in reservoir F
cannot flow freely to H by opening valve 7, because water cannot flow uphill. If, however, valves 1, 2, 5, and 7 are
open, water flows from F to H, because the energy conserved during the downhill flow of water through valves 1, 2,
and 5 is sufficient to allow it to force the water up through valve 7. In a similar way, enzymes in the metabolic
pathway cannot convert compound F directly to H unless energy is available; enzymes are able to utilize energy
from energy-conserving reactions in order to catalyze reactions that require energy. During the enzyme-catalyzed
oxidation of carbohydrates to carbon dioxide and water, energy is conserved in the form of an energy-rich
compound, adenosine triphosphate (ATP). The energy in ATP is utilized during an energy-consuming process such
as the enzyme-catalyzed contraction of muscle.

Because the needs of cells and organisms vary, not only the activity but also the synthesis of enzymes must be
regulated; e.g., the enzymes responsible for muscular activity in a leg muscle must be activated and inhibited at
appropriate times. Some cells do not need certain enzymes; a liver cell, for example, does not need a muscle
enzyme. A bacterium does not need enzymes to metabolize substances that are not present in its growth medium.
 63

Some enzymes, therefore, are not formed in certain cells, others are synthesized only when required, and still others
are found in all cells. The formation and activity of enzymes are regulated not only by genetic mechanisms but also
by organic secretions (hormones) from endocrine glands and by nerve impulses. Small molecules also play an
important role (see below Enzyme flexibility and allosteric control).

If an enzyme is defective in some respect, disease may occur. The enzymes represented by the numbers 1 to 4 in the
diagram must function during the conversion of the starting substance A to the product E. If one step is blocked
because an enzyme is unable to function, product E may not be formed; if E is necessary for some vital function,
disease results. Many inherited diseases and conditions of humans result from a deficiency of one enzyme.
Albinism, for example, results from an inherited lack of ability to synthesize the enzyme tyrosinase, which catalyzes
one step in the pathway by which the pigment for hair and eye colour is formed.

Enzymes identified with hereditary diseases

disease name defective enzyme
albinism tyrosinase
phenylketonuria phenylalanine hydroxylase
fructosuria fructokinase
methemoglobinemia methemoglobin reductase
galactosemia galactose-1-phosphate uridyl transferase

Other functions
Enzymes play an increasingly important role in medicine. The enzyme thrombin is used to promote the healing of
wounds. Other enzymes are used to diagnose certain kinds of disease, to cause the remission of some forms of
leukemia—a disease of the blood-forming organs—and to counteract unfavourable reactions in people who are
allergic to penicillin. The enzyme lysozyme, which destroys cell walls, is used to kill bacteria. Enzymes have also
been investigated for their potential to prevent tooth decay and to serve as anticoagulants in the treatment of
thrombosis, a disease characterized by the formation of a clot, or plug, in a blood vessel. Enzymes may eventually
be used to control enzyme deficiencies and abnormalities resulting from diseases.

It might also be noted in passing that enzymes are used in industrial processes involving the preparation of certain
chemical compounds and the tanning of leather. They also are valuable in analytical procedures involving the
detection of very small quantities of specific substances. Enzymes are necessary in various food-related industries,
including cheese making, the brewing of beer, the aging of wine, and the baking of bread. Enzymes also may be
used to clean clothes. For some industrial uses of enzymes, see baking.

General properties

Classification and nomenclature

The first enzyme name, proposed in 1833, was diastase. Sixty-five years later, French microbiologist and chemist
Émile Duclaux suggested that all enzymes be named by adding -ase to a root indicative of the nature of the substrate
of the enzyme. Although enzymes are no longer named in such a simple manner, with the exception of a few—e.g.,
pepsin, trypsin, chymotrypsin, papain—most enzyme names do end in -ase.

Any systematic classification of enzymes should be based on a common property or quality that varies sufficiently
to be useful as a distinguishing feature. In this regard, three properties of enzymes could serve as a basis for enzyme
classification—the exact chemical nature of the enzyme, the chemical nature of the substrate, and the nature of the
reaction catalyzed. In addition, although, as indicated above, early attempts at enzyme classification were based on
 64

the nature of broad groups of substrates (e.g., enzymes called carbohydrases act on carbohydrates), close functional
similarities among enzymes in different groups were often obscured. By general agreement, enzymes now are
classified according to their substrates and the nature of the reaction they catalyze.

In an attempt to devise a rational system of enzyme nomenclature, two names are given to an enzyme. One, known
as the systematic name, is based on logical principles but is often long and awkward; the other, “trivial” name is
short and generally used but not usually exact or systematic. In the scheme of systematic nomenclature, six main
groups of enzymatic reactions are recognized; each catalyzes one reaction type and is subdivided on the basis of
detailed definitions of the reaction catalyzed and of the substrate involved in the reaction. Enzymes that catalyze
reactions in which hydrogen is transferred belong to the group known as oxidoreductases; those that catalyze the
introduction of the elements of water at a specific site in a molecule are called hydrolases. The other four groups of
reactions are the transferases—which catalyze reactions in which substances other than hydrogen are transferred—
the lyases, the isomerases, and the ligases. Oxidoreductases and transferases account for about 50 percent of the
approximately 1,000 enzymes recognized thus far.
Classification of some enzymes
systematic name* trivial name reaction catalyzed biological role
code
name***
number**
alcohol: NAD alcohol + NAD → acetaldehyde alcoholic
1.1.1.1 alcohol dehydrogenase
oxidoreductase NADH fermentation
L-lactate: NAD lactate + NAD → pyruvate + carbohydrate
1.1.1.27 lactic dehydrogenase
oxidoreductase NADH metabolism
pyruvic acid + ATP →
ATP: pyruvate carbohydrate
2.7.1.40 pyruvate kinase phosphoenolpyruvic acid +
phosphotransferase metabolism
ADP
acetylcholine: acetylcholine + H2O → acetate nerve-impulse
3.1.1.7 acetylcholinesterase
acetylhydrolase + choline conduction
*Based on recommendations (1964) of the International Union of Biochemistry.
**The numbering system is as follows: the first number places the enzyme in one of six general groups—1,
oxidoreductases; 2, transferases; 3, hydrolases; 4, lyases; 5, iomerases; and 6, ligases. The second number places the
enzyme in a subclass based on substrate type or reaction type; e.g., the enzyme may act on molecules with −CHOH
groups. The third number places the enzyme in a subsubclass, which specifies the reaction type more fully; e.g.,
NAD coenzyme required. The fourth number is the serial number of the enzyme in its subsubclass.
***NAD and NADH represent the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD),
respectively; ATP and ADP represent adenosine triphosphate and adenosine diphosphate, respectively.

Chemical nature
Little was known about the chemical nature of enzymes until the beginning of the 20th century, although scientists
were almost convinced that they were proteins. In 1926 the enzyme urease was the first to be crystallized and clearly
identified as a protein. Within the next few years the digestive enzymes pepsin, trypsin, and chymotrypsin were
shown to be proteins. Since that time hundreds of enzymes, all of them proteins, have been prepared and
characterized by chemical methods. Much of the knowledge of protein chemistry has, in fact, resulted from studies
involving enzymes and from attempts to understand their nature and mode of action.

Although some enzymes consist of a single chain of the amino acids (i.e., simple organic molecules containing
nitrogen), most enzymes are composed of more than one chain. Each chain is called a subunit. Many enzymes have
two, four, or six subunits, and some consist of as many as 12 to 60 subunits. In many cases the subunits have
identical structures; in others, however, several different types of subunit chains are involved.
 65

With the exception of proteins that act as structural elements, most of the proteins in physiologically active tissues
such as kidney and liver are enzymes. Regardless of the exact amount of enzymatic protein in an organism, it is
clear that hundreds of different enzymes must be present in each tissue to account for the myriad reactions
composing metabolism.

Cofactors
Although some enzymes consist only of protein, many are complex proteins; i.e., they have a protein component and
a so-called cofactor. A complete enzyme is called a holoenzyme; if the cofactor is removed, the protein, no longer
enzymatically active, is called the apoenzyme. A cofactor may be a metal—such as iron, copper, or magnesium—a
moderately sized organic molecule called a prosthetic group, or a special type of substrate molecule known as a
coenzyme. The cofactor may aid in the catalytic function of an enzyme, as do metals and prosthetic groups, or take
part in the enzymatic reaction, as do coenzymes.

A coenzyme serves as a type of substrate in certain enzymatic reactions and thus reacts in the exact proportions (i.e.,
stoichiometrically) required for reaction, rather than in catalytic quantities. A coenzyme may, for example, assume
the role of a hydrogen acceptor, as does nicotinamide adenine dinucleotide (NAD), which accepts hydrogen from
the substrate, or a chemical-group donor, as does adenosine triphosphate (ATP), which donates phosphoric acid to
the substrate. After ATP has donated a phosphoric acid molecule to the substrate, the phosphoric acid can be
reacquired in a second stoichiometric reaction catalyzed by a second enzyme. The catalytic nature of a coenzyme is
apparent only when it couples the activities of two enzymes in this way. Coenzymes thus are the links, or shuttles, in
metabolic pathways that enable substances—e.g., hydrogen, phosphoric acid—to be exchanged.

The nature of enzyme-catalyzed reactions

The nature of catalysis

In a chemical reaction—for example, one in which substance A is converted into product B—a point of equilibrium
eventually is reached at which no further chemical change occurs; i.e., the rate of conversion of A to B equals the
rate of conversion of B to A. The so-called thermodynamic-equilibrium constant expresses this chemical
equilibrium. A catalyst may be defined as a substance that accelerates a chemical reaction but is not consumed in the
process. The amount of catalyst has no relationship to the quantity of substance altered; very small amounts of
enzymes are very efficient catalysts. Because the presence of an enzyme accelerates the rate of conversion of a
compound to a product, it accelerates the approach to equilibrium; it does not, however, influence the equilibrium
point attained.

The molecules in the watery medium of the cell are in constant thermal motion but, because they are more or less
stable compounds, they would react only occasionally to form products in the absence of enzymes. There exists an
energy barrier to the reaction of a molecule. The energy required to overcome the barrier to reaction is called the
energy of activation. A reaction proceeds to equilibrium only if the molecules have sufficient energy of activation to
form an activated complex, from which products can be derived. Enzymes greatly increase the chances for reactions
by their ability to make large numbers of specific molecules more reactive (i.e., unstable) by forming intermediate
compounds with them. The unstable intermediates quickly break down to form stable products, and the enzymes,
unchanged by the reaction, are able to catalyze the formation of additional products.

AMINO ACIDS

Amino acid, any of a group of organic molecules that consist of a basic amino group (−NH2), an acidic carboxyl
group (−COOH), and an organic R group (or side chain) that is unique to each amino acid. The term amino acid is
short for α-amino [alpha-amino] carboxylic acid. Each molecule contains a central carbon (C) atom, called the α-
carbon, to which both an amino and a carboxyl group are attached. The remaining two bonds of the α-carbon atom
are generally satisfied by a hydrogen (H) atom and the R group. The formula of a general amino acid is:
 66

The amino acids differ from each other in the particular chemical structure of the R group.

Building blocks of proteins

Proteins are of primary importance to the continuing functioning of life on Earth. Proteins catalyze the vast majority
of chemical reactions that occur in the cell. They provide many of the structural elements of a cell, and they help to
bind cells together into tissues. Some proteins act as contractile elements to make movement possible. Others are
responsible for the transport of vital materials from the outside of the cell (“extracellular”) to its inside
(“intracellular”). Proteins, in the form of antibodies, protect animals from disease and, in the form of interferon,
mount an intracellular attack against viruses that have eluded destruction by the antibodies and other immune system
defenses. Many hormones are proteins. Last but certainly not least, proteins control the activity of genes (“gene
expression”).

This plethora of vital tasks is reflected in the incredible spectrum of known proteins that vary markedly in their
overall size, shape, and charge. By the end of the 19th century, scientists appreciated that, although there exist many
different kinds of proteins in nature, all proteins upon their hydrolysis yield a class of simpler compounds, the
building blocks of proteins, called amino acids. The simplest amino acid is called glycine, named for its sweet taste
(glyco, “sugar”). It was one of the first amino acids to be identified, having been isolated from the protein gelatin in
1820. In the mid-1950s scientists involved in elucidating the relationship between proteins and genes agreed that 20
amino acids (called standard or common amino acids) were to be considered the essential building blocks of all
proteins. The last of these to be discovered, threonine, had been identified in 1935.

Some common uses

The industrial production of amino acids is an important worldwide business. The first report of the commercial
production of an amino acid was in 1908. It was then that the flavouring agent monosodium glutamate (MSG) was
prepared from a type of large seaweed. This led to the commercial production of MSG, which is now produced
using a bacterial fermentation process with starch and molasses as carbon sources. Glycine, cysteine, and d,l-alanine
are also used as food additives, and mixtures of amino acids serve as flavour enhancers in the food industry. The
amino acid balance of soy or corn protein for animal feed is significantly enhanced upon the addition of the
nutritionally limiting amino acids methionine and lysine.

Amino acids are used therapeutically for nutritional and pharmaceutical purposes. For example, patients are often
infused with amino acids to supply these nutrients before and after surgical procedures. Treatments with single
amino acids are part of the medical approach to control certain disease states. Examples include l-
dihydroxyphenylalanine (l-dopa) for Parkinson disease; glutamine and histidine to treat peptic ulcers; and arginine,
citrulline, and ornithine to treat liver diseases.

Certain derivations of amino acids, especially of glutamate, are used as surfactants in mild soaps and shampoos. d-
Phenylglycine and d-hydroxyphenylglycine are intermediates used for the chemical synthesis of β-lactam antibiotics
(e.g., synthetic versions of penicillin). Aspartame is a sweetener prepared from the individual component amino
acids aspartic acid and phenylalanine.

Amino acids and the origin of life on Earth

The question of why organisms on Earth consist of l-amino acids instead of d-amino acids is still an unresolved
riddle. Some scientists have long suggested that a substantial fraction of the organic compounds that were the
precursors to amino acids—and perhaps some amino acids themselves—on early Earth may have been derived from
comet and meteorite impacts. One such organic-rich meteorite impact occurred on September 28, 1969, over
Murchison, Victoria, Australia. This meteorite is suspected to be of cometary origin because of its high water
content of 12 percent. Dozens of different amino acids have been identified within the Murchison meteorite, some of
 67

which are found on Earth. Some compounds identified in the meteorite, however, have no apparent terrestrial
source. Most intriguing are the reports that amino acids in the Murchison meteorite exhibit an excess of l-amino
acids. An extraterrestrial source for an l-amino acid excess in the solar system could predate the origin of life on
Earth and thus explain the presence of a similar excess of l-amino acids on the prelife Earth.

Chirality
All the amino acids but glycine are chiral molecules. That is, they exist in two optically active asymmetric forms
(called enantiomers) that are the mirror images of each other. (This property is conceptually similar to the spatial
relationship of the left hand to the right hand.) One enantiomer is designated d and the other l. It is important to note
that the amino acids found in proteins almost always possess only the l-configuration. This reflects the fact that the
enzymes responsible for protein synthesis have evolved to utilize only the l-enantiomers. Reflecting this near
universality, the prefix l is usually omitted. Some d-amino acids are found in microorganisms, particularly in the cell
walls of bacteria and in several of the antibiotics. However, these are not synthesized in the ribosome.

Acid-base properties
Another important feature of free amino acids is the existence of both a basic and an acidic group at the α-carbon.
Compounds such as amino acids that can act as either an acid or a base are called amphoteric. The basic amino
group typically has a pKa between 9 and 10, while the acidic α-carboxyl group has a pKa that is usually close to 2 (a
very low value for carboxyls). The pKa of a group is the pH value at which the concentration of the protonated
group equals that of the unprotonated group. Thus, at physiological pH (about 7–7.4), the free amino acids exist
largely as dipolar ions or “zwitterions” (German for “hybrid ions”; a zwitterion carries an equal number of positively
and negatively charged groups). Any free amino acid and likewise any protein will, at some specific pH, exist in the
form of a zwitterion. That is, all amino acids and all proteins, when subjected to changes in pH, pass through a state
at which there is an equal number of positive and negative charges on the molecule. The pH at which this occurs is
known as the isoelectric point (or isoelectric pH) and is denoted as pI. When dissolved in water, all amino acids and
all proteins are present predominantly in their isoelectric form. Stated another way, there is a pH (the isoelectric
point) at which the molecule has a net zero charge (equal number of positive and negative charges), but there is no
pH at which the molecule has an absolute zero charge (complete absence of positive and negative charges). That is,
amino acids and proteins are always in the form of ions; they always carry charged groups. This fact is vitally
important in considering further the biochemistry of amino acids and proteins.

Standard amino acids

One of the most useful manners by which to classify the standard (or common) amino acids is based on the polarity
(that is, the distribution of electric charge) of the R group (e.g., side chain).

Group I: Nonpolar amino acids

Group I amino acids are glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, and
tryptophan. The R groups of these amino acids have either aliphatic or aromatic groups. This makes them
hydrophobic (“water fearing”). In aqueous solutions, globular proteins will fold into a three-dimensional shape to
bury these hydrophobic side chains in the protein interior. The chemical structures of Group I amino acids are:
 68

Isoleucine is an isomer of leucine, and it contains two chiral carbon atoms. Proline is unique among the standard
amino acids in that it does not have both free α-amino and free α-carboxyl groups. Instead, its side chain forms a
cyclic structure as the nitrogen atom of proline is linked to two carbon atoms. (Strictly speaking, this means that
proline is not an amino acid but rather an α-imino acid.) Phenylalanine, as the name implies, consists of a phenyl
group attached to alanine. Methionine is one of the two amino acids that possess a sulfur atom. Methionine plays a
central role in protein biosynthesis (translation) as it is almost always the initiating amino acid. Methionine also
provides methyl groups for metabolism. Tryptophan contains an indole ring attached to the alanyl side chain.

Group II: Polar, uncharged amino acids

Group II amino acids are serine, cysteine, threonine, tyrosine, asparagine, and glutamine. The side chains in this
group possess a spectrum of functional groups. However, most have at least one atom (nitrogen, oxygen, or sulfur)
with electron pairs available for hydrogen bonding to water and other molecules. The chemical structures of Group
II amino acids are:

Two amino acids, serine and threonine, contain aliphatic hydroxyl groups (that is, an oxygen atom bonded to a
hydrogen atom, represented as −OH). Tyrosine possesses a hydroxyl group in the aromatic ring, making it a phenol
derivative. The hydroxyl groups in these three amino acids are subject to an important type of posttranslational
modification: phosphorylation (see below Nonstandard amino acids). Like methionine, cysteine contains a sulfur
atom. Unlike methionine’s sulfur atom, however, cysteine’s sulfur is very chemically reactive (see below Cysteine
oxidation). Asparagine, first isolated from asparagus, and glutamine both contain amide R groups. The carbonyl
group can function as a hydrogen bond acceptor, and the amino group (NH2) can function as a hydrogen bond donor.

Group III: Acidic amino acids

The two amino acids in this group are aspartic acid and glutamic acid. Each has a carboxylic acid on its side chain
that gives it acidic (proton-donating) properties. In an aqueous solution at physiological pH, all three functional
groups on these amino acids will ionize, thus giving an overall charge of −1. In the ionic forms, the amino acids are
called aspartate and glutamate. The chemical structures of Group III amino acids are

The side chains of aspartate and glutamate can form ionic bonds (“salt bridges”), and they can also function as
hydrogen bond acceptors. Many proteins that bind metal ions (“metalloproteins”) for structural or functional
purposes possess metal-binding sites containing aspartate or glutamate side chains or both. Free glutamate and
glutamine play a central role in amino acid metabolism. Glutamate is the most abundant excitatory neurotransmitter
in the central nervous system.

Group IV: Basic amino acids

The three amino acids in this group are arginine, histidine, and lysine. Each side chain is basic (i.e., can accept a
proton). Lysine and arginine both exist with an overall charge of +1 at physiological pH. The guanidino group in
arginine’s side chain is the most basic of all R groups (a fact reflected in its pKa value of 12.5). As mentioned above
for aspartate and glutamate, the side chains of arginine and lysine also form ionic bonds.

The imidazole side chain of histidine allows it to function in both acid and base catalysis near physiological pH
values. None of the other standard amino acids possesses this important chemical property. Therefore, histidine is an
amino acid that most often makes up the active sites of protein enzymes.
 69

The majority of amino acids in Groups II, III, and IV are hydrophilic (“water loving”). As a result, they are often
found clustered on the surface of globular proteins in aqueous solutions.

Amino acid reactions

Amino acids via their various chemical functionalities (carboxyls, amino, and R groups) can undergo numerous
chemical reactions. However, two reactions (peptide bond and cysteine oxidation) are of particular importance
because of their effect on protein structure.

Peptide bond
Amino acids can be linked by a condensation reaction in which an −OH is lost from the carboxyl group of one
amino acid along with a hydrogen from the amino group of a second, forming a molecule of water and leaving the
two amino acids linked via an amide—called, in this case, a peptide bond. At the turn of the 20th century, German
chemist Emil Fischer first proposed this linking together of amino acids. Note that when individual amino acids are
combined to form proteins, their carboxyl and amino groups are no longer able to act as acids or bases, since they
have reacted to form the peptide bond. Therefore, the acid-base properties of proteins are dependent upon the overall
ionization characteristics of the individual R groups of the component amino acids.

Amino acids joined by a series of peptide bonds are said to constitute a peptide. After they are incorporated into a
peptide, the individual amino acids are referred to as amino acid residues. Small polymers of amino acids (fewer
than 50) are called oligopeptides, while larger ones (more than 50) are referred to as polypeptides. Hence, a protein
molecule is a polypeptide chain composed of many amino acid residues, with each residue joined to the next by a
peptide bond. The lengths for different proteins range from a few dozen to thousands of amino acids, and each
protein contains different relative proportions of the 20 standard amino acids.

Cysteine oxidation
The thiol (sulfur-containing) group of cysteine is highly reactive. The most common reaction of this group is a
reversible oxidation that forms a disulfide. Oxidation of two molecules of cysteine forms cystine, a molecule that
contains a disulfide bond. When two cysteine residues in a protein form such a bond, it is referred to as a disulfide
bridge. Disulfide bridges are a common mechanism used in nature to stabilize many proteins. Such disulfide bridges
are often found among extracellular proteins that are secreted from cells. In eukaryotic organisms, formation of
disulfide bridges occurs within the organelle called the endoplasmic reticulum.

In extracellular fluids (such as blood), the sulfhydryl groups of cysteine are rapidly oxidized to form cystine. In a
genetic disorder known as cystinuria, there is a defect that results in excessive excretion of cystine into the urine.
Because cystine is the least soluble of the amino acids, crystallization of the excreted cystine results in formation of
calculi—more commonly known as “stones”—in the kidney, ureter, or urinary bladder. The stones may cause
intense pain, infection, and blood in the urine. Medical intervention often involves the administration of d-
penicillamine. Penicillamine works by forming a complex with cystine; this complex is 50 times more water-soluble
than cystine alone.

In summary, it is the sequence of amino acids that determines the shape and biological function of a protein as well
as its physical and chemical properties. Thus, the functional diversity of proteins arises because proteins are
polymers of 20 different kinds of amino acids. For example, a “simple” protein is the hormone insulin, which has 51
amino acids. With 20 different amino acids to chose from at each of these 51 positions, a total of 2051, or about 1066,
different proteins could theoretically be made.

Other functions
Amino acids are precursors of a variety of complex nitrogen-containing molecules. Prominent among these are the
nitrogenous base components of nucleotides and the nucleic acids (DNA and RNA). Furthermore, there are complex
amino-acid derived cofactors such as heme and chlorophyll. Heme is the iron-containing organic group required for
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the biological activity of vitally important proteins such as the oxygen-carrying hemoglobin and the electron-
transporting cytochrome c. Chlorophyll is a pigment required for photosynthesis.

•
Portion of polynucleotide chain of deoxyribonucleic acid (DNA). The inset shows the corresponding …

Encyclopædia Britannica, Inc.

Several α-amino acids (or their derivatives) act as chemical messengers. For example, γ-aminobutyric acid (gamma-
aminobutyric acid, or GABA; a derivative of glutamic acid), serotonin and melatonin (derivatives of tryptophan),
and histamine (synthesized from histidine) are neurotransmitters. Thyroxine (a tyrosine derivative produced in the
thyroid gland of animals) and indole acetic acid (a tryptophan derivative found in plants) are two examples of
hormones.

Several standard and nonstandard amino acids often are vital metabolic intermediates. Important examples of this
are the amino acids arginine, citrulline, and ornithine, which are all components of the urea cycle. The synthesis of
urea is the principal mechanism for the removal of nitrogenous waste.

Nonstandard amino acids

Nonstandard amino acids refer to those amino acids that have been chemically modified after they have been
incorporated into a protein (called a “posttranslational modification”) and those amino acids that occur in living
organisms but are not found in proteins. Among these modified amino acids is γ-carboxyglutamic acid, a calcium-
binding amino acid residue found in the blood-clotting protein prothrombin (as well as in other proteins that bind
calcium as part of their biological function). The most abundant protein by mass in vertebrates is collagen.
Significant proportions of the amino acids in collagen are modified forms of proline and lysine: 4-hydroxyproline
and 5-hydroxylysine.

•
Genes are made up of promoter regions and alternating regions of introns (noncoding sequences) and …

Encyclopædia Britannica, Inc.

Arguably, the most important posttranslational modification of amino acids in eukaryotic organisms (including
humans) is the reversible addition of a phosphate molecule to the hydroxyl portion of the R groups of serine,
threonine, and tyrosine. This event is known as phosphorylation and is used to regulate the activity of proteins in
their minute-to-minute functioning in the cell. Serine is the most commonly phosphorylated residue in proteins,
threonine is second, and tyrosine is third.

Proteins with carbohydrates (sugars) covalently attached to them are called glycoproteins. Glycoproteins are widely
distributed in nature and provide the spectrum of functions already discussed for unmodified proteins. The sugar
groups in glycoproteins are attached to amino acids through either oxygen (O-linked sugars) or nitrogen atoms (N-
linked sugars) in the amino acid residues. The O-linked sugars are attached to proteins through the oxygen atoms in
serine, threonine, hydroxylysine, or hydroxylproline residues. The N-linked sugars are attached to proteins through
the nitrogen atom in asparagine.

Finally, there is the case of selenocysteine. Although it is part of only a few known proteins, there is a sound
scientific reason to consider this the 21st amino acid because it is in fact introduced during protein biosynthesis
rather than created by a posttranslational modification. Selenocysteine is actually derived from the amino acid serine
(in a very complicated fashion), and it contains selenium instead of the sulfur of cysteine.
 71

10. CANCER TERMS

Cancer is a scary word, but as you have learned by now, words give you the information you need to make
knowledgeable decisions in consultation with your family physician and oncologist (cancer specialist).

Many cancer terms are unique to the field of oncology (study of tumors) and don’t lend themselves easily to the
prefix, root, suffix system used in the previous modules. Instead, terms will be grouped and defined in broad
categories such as tumor types, causes and treatments. In place of a quiz there will be a simulated case that
reinforces frequently used terms.

Cancer buzz words

Good news Bad news

Benign Malignant
Low grade High grade
Radiosensitive Radioresistant
No metastases metastases
Well differentiated Poorly differentiated
Negative nodes Positive nodes
In remission Relapse
Surgically resectable Inoperable
Tumor types

Malignant vs. benign (literally, “evil” versus “good”)

Tumors are masses of cells that have slipped the bonds of control of cell multiplication. Malignant tumors, cancers,
are life-threatening because they are invasive (spread into surrounding organs) and metastasize (travel to other areas
of the body to form new tumors). Specifically, invasiveness results in penetration, compression and destruction of
surrounding tissue causing such problems as loss of organ function (liver, kidneys), difficulty breathing (lungs),
obstruction (intestines), possible catastrophic bleeding and severe pain.

Carcinoma

Carcinoma is the most common form of cancer. Carcinoma develops from sheets of cells that cover a surface
(example: skin) or line a body cavity (example: glandular lining of stomach). Some names for tumors of this type
would be: adenocarcinoma of the prostate, adenocarcinoma of the lung, gastric adenocarcinoma, hepatocellular
carcinoma (what organ is involved?). Note that the term carcinoma typically appears in the name.

Sarcoma

A rare form of cancer arises from connective and supportive tissues, examples: bone, fat, muscle, and other
connective tissues. Some names of this type of tumor would be: osteosarcoma (malignancy of bone), liposarcoma
(fat) and gastrointestinal stromal tumor. Note that the term sarcoma does not always appear in the name.

Grading and staging

Tumor biopsies (tissue samples) are examined microscopically to determine the type and degree of development. A
grading scale is used, usually Grade I to Grade IV, to describe tissue differentiation. Tumors that are well
differentiated (it still looks like the original source tissue) generally have a good clinical outcome. Tumors that are
 72

poorly differentiated (the tissue has taken on a more primitive structure and may not resemble its original tissue)
generally have a poorer outcome. The clinical stage of a tumor is determined by physical exam (Can you feel the
tumor? Can you palpate (feel) lymph nodes? Is the tumor fixed in place (adherent to other structures)? Imaging (CT,
MRI) is also an essential tool. The stage of the tumor determines if the tumor has invaded surrounding tissue,
involved lymphatics (drainage channels for cell fluids other than blood) and whether the cancer has metastasized to
other sites in the body.

A staging system using the letters T, N, M is also used in conjunction with Grading. “T” indicates size of tumor;
“N” whether the cancer has spread into lymph nodes; “M” whether cancer cells have metastasized to other organs
and areas. For example, a melanoma T2N0M0 describes a skin cancer that is between 1.0 and 2.0 mm in thickness,
but has not spread into lymph nodes or other areas of the body.

Grading and staging tumors are important ways to predict the “prognosis” (progress and outcome of the disease),
and which types of treatments may most likely succeed. In general, low grade tumors that have not invaded tissues,
have not involved lymph nodes (negative nodes) and have not metastasized would be expected to have a better
prognosis than a high grade tumor that has invaded tissues, has invaded lymphatics (positive nodes) and has
metastasized. However, the prognosis of any individual patient is much more complicated than described here.
Complicating factors include the general health of the patient, the effectiveness of their immune system and
available treatment options. Some tumor types are very “aggressive” and are highly resistant to treatment.

Causes of cancer

Any injury to DNA (the genetic code) may result in the loss of cell cycle control, leading to uninhibited cell
division. Carcinogens are cancer causing agents. Broad categories include radiation, chemicals, drugs and viruses.
Don’t panic! Your once a year dental X-ray and common cold and flu viruses will not cause cancer. However,
excessive radiation from nuclear to sunlight can significantly increase your risk of malignancy. The Human
Papilloma Virus (HPV) is the major cause of cervical cancer. Environmental chemicals found in tobacco smoke,
automotive exhaust, toxic emissions from factory smokestacks and asbestos exposure are all carcinogenic.

Curious about your risk for common cancers? Check in at Your Disease Risk at Washington University School of
Medicine.

Cancer Therapy

Tumor markers

Tumor markers are substances that are produced by tumors or the body’s response to presence of a tumor. Tumor
markers found in various body fluids, such as the blood, can be useful in the detection and response to treatment of
certain cancers. However, most tumor markers are not specific for cancer and they may be present or even elevated
with benign diseases. The absence of a tumor marker can also be useful in confirming successful cancer treatment;
whereas an increase in the tumor marker level may indicate recurrence. Two well known markers are Prostate
Specific Antigen (PSA) for prostate cancer and CA-125 for ovarian cancer.

Radiation

It is ironic that the same agent that can cause cancer can be used to destroy cancer, but a common mechanism is at
work. Fairly low to moderate doses of radiation can cause DNA damage, which may result in the malignant
transformation of normal cells into cancer cells. But, high dose radiation focused on cells can destroy the cancerous
cells. However, even with highly focused radiation treatment, normal surrounding tissues are exposed to the
radiation and may lead to secondary cancers.

Some terms you will hear about are:

Radiosensitive – cancer degenerates in response to radiation

 73

Radioresistant – the cancer may have a partial response or doesn’t respond at all

Fractionation – a treatment radiation dose is broken down into multiple exposures over several weeks to minimize
side effects

Chemotherapy

Perhaps nothing short of surgery strikes fear into our hearts more than being told, “You’re going to need chemo”.
Stories of hair falling out and nausea and/or diarrhea are awful. But, the essential action of most chemotherapeutic
agents is to kill or stop the development of rapidly dividing cells. However, chemotherapy works systemically
(affects the whole body) so any rapidly dividing cell, cancer or not, is affected by the medication; such as hair
follicles and the lining cells of our stomach/intestines. Make sense?

Another side effect of chemotherapy is myelosuppression, where the rapidly dividing bone marrow cells are killed
off. Patients may complain of extreme fatigue due to anemia (reduced number of erythrocytes) and can be at
increased risk of infectious disease (reduced number of leucocytes).

Chemotherapeutic agents that you will likely hear about are: Cisplatin, Carboplatin, Bleomycin, 5-fluorouracil,
methotrexate, Vincristine, Vinblastine, and Taxol. Since the same mechanism that kills a malignant cell or blocks
development of a malignant cell can have similar effects on a normal, rapidly dividing cell, any of these agents can
have unpleasant side effects. Some forms of cancer treated with chemotherapy may cause the cancer to “disappear”
for awhile although not cured and the patient may be symptom free sometimes for months or years. This period of
holding the cancer in check is called a “remission”. Unfortunately, many such cancers, such as leukemia, reoccur
and the patient is said to have “relapsed”.

Every year, promising new treatments are being developed. One of the newest is an angiogenesis (blood vessel
growing) inhibitor. Medications such as Avastin and Sutent block blood vessels from growing into a tumor thereby
starving the growth.

Surgery

In my opinion, the best way to get rid of a cancer is cut it out. I want rid of it now! However, some tumors are so
enmeshed in normal tissues that they cannot be safely cut out without severe damage to normal tissues, in other
words, they are “inoperable”. And, depending upon the location (brain, prostate, etc) and the amount of excised
tissue, one may be left with severe disability. However, surgery can be a complete cure for some types of tumors if
done early, such as malignant melanoma (skin cancer). The probability of a cure may be enhanced after surgery by
following up with additional treatments such as chemotherapy, radiation therapy or both. The term for this is
“adjuvant therapy”.

Some surgical terms you will hear:

Cryosurgery – destroying malignant tissue by freezing it with a cold probe. Often used for soft tissues like liver or
kidney.

Fulguration – “Lightning” in Latin. Malignant tissue is destroyed with an electrocautery instrument (electric
current).

Excisional biopsy – simultaneous tissue sampling and removal of a tumor with a safe margin of normal tissue.
Frequently done with suspicious skin lesions; example, malignant melanoma.

Resect- to cut and remove a segment of an organ containing a tumor.

En bloc resection – removal of the tumor and any surrounding organs or tissues that may be involved. This is often
necessary for large abdominal sarcomas.
 74

Unfortunately, not all cancer treatments are curative. Palliative treatment gives relief of symptoms, but does not cure
and is reserved for advanced malignancy.

THE IMMUNE SYSTEM AND ZINC

IMMUNE SYSTEM AND ZINC

Zinc and immune function: the biological basis of altered resistance to infection.

Zinc is thought by many nutritionists to be the most important mineral supplement because it is commonly deficient
in the diet. Zinc is the nutrient that aids the immune system.
Essential to human growth, zinc is key to proper T cell and natural killer cell function and proper lymphocyte
activity; it may be directly involved in antibody production to help you fight infection. Zinc is essential to many
enzyme systems and for normal functioning of the immune system.
Key functions of zinc:

• Functions in a multitude of enzymes — for alcohol and amino acid metabolism, protein digestion, and
energy production, as well as in immune function and in the body’s fight against damaging free radicals.

• Used by men to support good prostate and reproductive health.

• Particularly important for teenagers during sexual development.

• Used to support optimum immune function. Zinc lozenges are famous, with some good clinical studies to
their credit, for helping your immune system fight off colds and sore throats and recover from injury,
illness, or surgery.

• May protect you against the toxic effects of chemical exposures.

Adequate amounts of zinc are not always easy to get from your foods. This nutrient is as important for good plant
health as it is for human health. Zinc, like most other minerals, needs to be abundant in healthy soil for plants to
absorb it and for your food to supply you with an ample amount.
Zinc is found in oysters (which have the highest zinc content by far), shellfish, meats, eggs, whole grains, nuts, and
seeds. Pumpkin and squash seeds are especially good sources.
Normal supplementation is about 15–30 mg daily in men and 10–20 mg in women; you can use more zinc
temporarily, to correct deficiency. Remember to take copper (2–3 mg) and manganese (5–10 mg), if you increase
your zinc intake.

Zinc can cause toxic reactions in your body, such as abdominal pain, nausea, and vomiting, when you take too
much. Deficiency is somewhat common and can cause more infections and a weakened immune function, delayed
sexual development in boys and girls, and prostate problems in men.
 75

Other common symptoms of zinc deficiency include loss of appetite, impaired senses of smell and taste, growth
retardation, delayed wound healing, depression, impaired concentration, nervousness, night blindness, and slowed
nail and hair growth.

Zinc is known to play a central role in the immune system, and zinc-deficient persons experience increased
susceptibility to a variety of pathogens. The immunologic mechanisms whereby zinc modulates increased
susceptibility to infection have been studied for several decades. It is clear that zinc affects multiple aspects of the
immune system, from the barrier of the skin to gene regulation within lymphocytes. Zinc is crucial for normal
development and function of cells mediating nonspecific immunity such as neutrophils and natural killer cells. Zinc
deficiency also affects development of acquired immunity by preventing both the outgrowth and certain functions of
T lymphocytes such as activation, Th1 cytokine production, and B lymphocyte help. Likewise, B lymphocyte
development and antibody production, particularly immunoglobulin G, is compromised. The macrophage, a pivotal
cell in many immunologic functions, is adversely affected by zinc deficiency, which can dysregulate intracellular
killing, cytokine production, and phagocytosis. The effects of zinc on these key immunologic mediators is rooted in
the myriad roles for zinc in basic cellular functions such as DNA replication, RNA transcription, cell division, and
cell activation. Apoptosis is potentiated by zinc deficiency. Zinc also functions as an antioxidant and can stabilize
membranes.

Immune system, the complex group of defense responses found in humans and other advanced vertebrates that
helps repel disease-causing organisms (pathogens). Immunity from disease is actually conferred by two cooperative
defense systems, called nonspecific, innate immunity and specific, acquired immunity. Nonspecific protective
mechanisms repel all microorganisms equally, while the specific immune responses are tailored to particular types
of invaders. Both systems work together to thwart organisms from entering and proliferating within the body. These
immune mechanisms also help eliminate abnormal cells of the body that can develop into cancer.

he following sections provide a detailed explanation of how nonspecific and specific immunity function and how the
immune system evolved. For information on how these systems can go awry and give rise to disease, see immune
system disorder. For additional information on leukemias, lymphomas, and myelomas, see the article cancer.

Mechanisms of the immune system

human disease: Diseases of immune origin

The immune system protects against infectious disease, but it may also at times cause disease. Disorders of the
immune system fall into two broad categories: (1) those that arise when some aspect of the host’s immune
mechanism fails to prevent infection (immune deficiencies) and (2) those that occur when the immune response is
directed at an inappropriate antigen, such as a noninfectious agent...
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Nonspecific, innate immunity

Most microorganisms encountered in daily life are repelled before they cause detectable signs and symptoms of
disease. These potential pathogens, which include viruses, bacteria, fungi, protozoans, and worms, are quite diverse,
and therefore a nonspecific defense system that diverts all types of this varied microscopic horde equally is quite
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useful to an organism. The innate immune system provides this kind of nonspecific protection through a number of
defense mechanisms, which include physical barriers such as the skin, chemical barriers such as antimicrobial
proteins that harm or destroy invaders, and cells that attack foreign cells and body cells harbouring infectious agents.
The details of how these mechanisms operate to protect the body are described in the following sections.

External barriers to infection

The skin and the mucous membrane linings of the respiratory, gastrointestinal, and genitourinary tracts provide the
first line of defense against invasion by microbes or parasites.

Skin

Human skin has a tough outer layer of cells that produce keratin. This layer of cells, which is constantly renewed
from below, serves as a mechanical barrier to infection. In addition, glands in the skin secrete oily substances that
include fatty acids, such as oleic acid, that can kill some bacteria; skin glands also secrete lysozyme, an enzyme
(also present in tears and saliva) that can break down the outer wall of certain bacteria. Victims of severe burns often
fall prey to infections from normally harmless bacteria, illustrating the importance of intact, healthy skin to a healthy
immune system.

Mucous membranes

Like the outer layer of the skin but much softer, the mucous membrane linings of the respiratory, gastrointestinal,
and genitourinary tracts provide a mechanical barrier of cells that are constantly being renewed. The lining of the
respiratory tract has cells that secrete mucus (phlegm), which traps small particles. Other cells in the wall of the
respiratory tract have small hairlike projections called cilia, which steadily beat in a sweeping movement that
propels the mucus and any trapped particles up and out of the throat and nose. Also present in the mucus are
protective antibodies, which are products of specific immunity. Cells in the lining of the gastrointestinal tract secrete
mucus that, in addition to aiding the passage of food, can trap potentially harmful particles or prevent them from
attaching to cells that make up the lining of the gut. Protective antibodies are secreted by cells underlying the
gastrointestinal lining. Furthermore, the stomach lining secretes hydrochloric acid that is strong enough to kill many
microbes.

Chemical barriers to infection

Some microbes penetrate the body’s protective barriers and enter the internal tissues. There they encounter a variety
of chemical substances that may prevent their growth. These substances include chemicals whose protective effects
are incidental to their primary function in the body, chemicals whose principal function is to harm or destroy
invaders, and chemicals produced by naturally occurring bacteria.

Chemicals with incidental protective effects

Some of the chemicals involved in normal body processes are not directly involved in defending the body against
disease. Nevertheless, they do help repel invaders. For example, chemicals that inhibit the potentially damaging
digestive enzymes released from body cells which have died in the natural course of events also can inhibit similar
enzymes produced by bacteria, thereby limiting bacterial growth. Another substance that provides protection against
microbes incidentally to its primary cellular role is the blood protein transferrin. The normal function of transferrin
is to bind molecules of iron that are absorbed into the bloodstream through the gut and to deliver the iron to cells,
which require the mineral to grow. The protective benefit transferrin confers results from the fact that bacteria, like
cells, need free iron to grow. When bound to transferrin, however, iron is unavailable to the invading microbes, and
their growth is stemmed.

Antimicrobial proteins

Complement
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A number of proteins contribute directly to the body’s nonspecific defense system by helping to destroy invading
microorganisms. One group of such proteins is termed complement because it works with other defense mechanisms
of the body, complementing their efforts to eradicate invaders. Many microorganisms can activate complement in
ways that do not involve specific immunity. Once activated, complement proteins work together to lyse, or break
apart, harmful infectious organisms that do not have protective coats. Other microorganisms can evade these
mechanisms but fall prey to scavenger cells, which engulf and destroy infectious agents, and to the mechanisms of
the specific immune response. Complement cooperates with both nonspecific and specific defense systems and is
described more fully under Antibody-mediated immune mechanisms.

Interferons

Another group of proteins that provide protection are the interferons, which inhibit the replication of many—but not
all—viruses. Cells that have been infected with a virus produce interferon, which sends a signal to other cells of the
body to resist viral growth. When first discovered in 1957, interferon was thought to be a single substance, but since
then several types have been discovered, each produced by a different type of cell. Alpha interferon is produced by
white blood cells other than lymphocytes, beta interferon by fibroblasts, and gamma interferon by natural killer cells
and cytotoxic T lymphocytes (killer T cells). All interferons inhibit viral replication by interfering with the
transcription of viral nucleic acid. Interferons exert additional inhibitory effects by regulating the extent to which
lymphocytes and other cells express certain important molecules on their surface membranes.

Proteins from naturally occurring bacteria

In the small and large intestines the growth of invading bacteria can be inhibited by naturally gut-dwelling bacteria
that do not cause disease. These gut-dwelling microorganisms secrete a variety of proteins that enhance their own
survival by inhibiting the growth of the invading bacterial species.

Cellular defenses

If an infectious agent is not successfully repelled by the chemical and physical barriers described above, it will
encounter cells whose function is to eliminate foreign substances that enter the body. These cells are the nonspecific
effector cells of the innate immune response. They include scavenger cells—i.e., various cells that attack infectious
agents directly—and natural killer cells, which attack cells of the body that harbour infectious organisms. Some of
these cells destroy infectious agents by engulfing and destroying them through the process of phagocytosis, while
other cells resort to alternative means. As is true of other components of innate immunity, these cells interact with
components of acquired immunity to fight infection.

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Time-lapse photography of a macrophage (the light-coloured, globular structure) consuming bacteria.

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Scavenger cells

All higher animals and many lower ones have scavenger cells—primarily leukocytes (white blood cells)—that
destroy infectious agents. Most vertebrates, including all birds and mammals, possess two main kinds of scavenger
cells. Their importance was first recognized in 1884 by the Russian biologist Élie Metchnikoff, who named them
microphages and macrophages, after Greek words meaning “little eaters” and “big eaters.”

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Macrophages, the principal phagocytic (cell-engulfing) components of the immune system, ingest and …
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Granulocytes

Microphages are now called either granulocytes, because of the numerous chemical-containing granules found in
their cytoplasm, or polymorphonuclear leukocytes, because of the oddly shaped nucleus these cells contain. Some
granules contain digestive enzymes capable of breaking down proteins, while others contain bacteriocidal (bacteria-
killing) proteins. There are three classes of granulocytes—neutrophils, eosinophils, and basophils—which are
distinguished according to the shape of the nucleus and the way in which the granules in the cytoplasm are stained
by dye. The differences in staining characteristics reflect differences in the chemical makeup of the granules.
Neutrophils are the most common type of granulocyte, making up about 60 to 70 percent of all white blood cells.
These granulocytes ingest and destroy microorganisms, especially bacteria. Less common are the eosinophils, which
are particularly effective at damaging the cells that make up the cuticle (body wall) of larger parasites. Fewer still
are the basophils, which release heparin (a substance that inhibits blood coagulation), histamine, and other
substances that play a role in some allergic reactions (see immune system disorder: Allergies). Very similar in
structure and function to basophils are the tissue cells called mast cells, which also contribute to immune responses.
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Granulocytes, which have a life span of only a few days, are continuously produced from stem (i.e., precursor) cells
in the bone marrow. They enter the bloodstream and circulate for a few hours, after which they leave the circulation
and die. Granulocytes are mobile and are attracted to foreign materials by chemical signals, some of which are
produced by the invading microorganisms themselves, others by damaged tissues, and still others by the interaction
between microbes and proteins in the blood plasma. Some microorganisms produce toxins that poison granulocytes
and thus escape phagocytosis; other microbes are indigestible and are not killed when ingested. By themselves, then,
granulocytes are of limited effectiveness and require reinforcement by the mechanisms of specific immunity.

Macrophages

The other main type of scavenger cell is the macrophage, the mature form of the monocyte. Like granulocytes,
monocytes are produced by stem cells in the bone marrow and circulate through the blood, though in lesser
numbers. But, unlike granulocytes, monocytes undergo differentiation, becoming macrophages that settle in many
tissues, especially the lymphoid tissues (e.g., spleen and lymph nodes) and the liver, which serve as filters for
trapping microbes and other foreign particles that arrive through the blood or the lymph. Macrophages live longer
than granulocytes and, although effective as scavengers, basically provide a different function. Compared with
granulocytes, macrophages move relatively sluggishly. They are attracted by different stimuli and usually arrive at
sites of invasion later than granulocytes. Macrophages recognize and ingest foreign particles by mechanisms that are
basically similar to those of granulocytes, although the digestive process is slower and not as complete. This aspect
is of great importance for the role that macrophages play in stimulating specific immune responses—something in
which granulocytes play no part (see Activation of T and B lymphocytes).

Natural killer (NK) cells

Natural killer cells do not attack invading organisms directly but instead destroy the body’s own cells that have
either become cancerous or been infected with a virus. NK cells were first recognized in 1975, when researchers
observed cells in the blood and lymphoid tissues that were neither the scavengers described above nor ordinary
lymphocytes but which nevertheless were capable of killing cells. Although similar in outward appearance to
lymphocytes, NK cells contain granules that harbour cytotoxic chemicals. NK cells recognize dividing cells by a
mechanism that does not depend on specific immunity. They then bind to these dividing cells and insert their
granules through the outer membrane and into the cytoplasm. This causes the dividing cells to leak and die. It is not
certain whether NK cells belong to a distinct lineage or are a special form of lymphocyte. It is known that they
produce gamma interferon. Their main biological role may be to regulate the growth of stem cells in the bone
marrow and elsewhere.

Nonspecific responses to infection

The body has a number of nonspecific methods of fighting infection that are called early induced responses. They
include the acute-phase response and the inflammation response, which can eliminate infection or hold it in check
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until specific, acquired immune responses have time to develop. Nonspecific immune responses occur more rapidly
than acquired immune responses do, but they do not provide lasting immunity to specific pathogens.

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Basic responses of the immune system.

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Nonadaptive immune responses rely on a number of chemical signals, collectively called cytokines, to carry out
their effects. These cytokines include members of the family of proteins called interleukins, which induce fever and
the acute-phase response, and tumour necrosis factor-alpha, which initiates the inflammatory response.

Acute-phase response

When the body is invaded by a pathogen, macrophages release the protein signals interleukin-1 (IL-1) and
interleukin-6 (IL-6) to help fight the infection. One of their effects is to raise the temperature of the body, causing
the fever that often accompanies infection. (The interleukins increase body temperature by acting on the
temperature-regulating hypothalamus in the brain and by affecting energy mobilization by fat and muscle cells.)
Fever is believed to be helpful in eliminating infections because most bacteria grow optimally at temperatures lower
than normal body temperature. But fever is only part of the more general innate defense mechanism called the acute-
phase response. In addition to raising body temperature, the interleukins stimulate liver cells to secrete increased
amounts of several different proteins into the bloodstream. These proteins, collectively called acute-phase proteins,
bind to bacteria and, by doing so, activate complement proteins that destroy the pathogen. The acute-phase proteins
act similarly to antibodies but are more democratic—that is, they do not distinguish between pathogens as antibodies
do but instead attack a wide range of microorganisms equally. Another effect the interleukins have is to increase the
number of circulating neutrophils and eosinophils, which help fight infection.

Inflammatory response

Infection often results in tissue damage, which may trigger an inflammatory response. The signs of inflammation
include pain, swelling, redness, and fever, which are induced by chemicals released by macrophages. These
substances promote blood flow to the area, increase the permeability of capillaries, and induce coagulation. The
increased blood flow is responsible for redness, and the leakiness of the capillaries allows cells and fluids to enter
tissues, causing pain and swelling. These effects bring more phagocytic cells to the area to help eliminate the
pathogens. The first cells to arrive, usually within an hour, are neutrophils and eosinophils, followed a few hours
later by macrophages. Macrophages not only engulf pathogens but also help the healing process by disposing of
cellular debris which accumulates from destroyed tissue cells and neutrophils that self-destruct after ingesting
microorganisms. If infection persists, components of specific immunity—antibodies and T cells—arrive at the site to
fight the infection.

Specific, acquired immunity

It has been known for centuries that persons who contract certain diseases and survive generally do not catch those
illnesses again. The Greek historian Thucydides recorded that, when the plague was raging in Athens during the 5th
century bc, the sick and dying would have received no nursing at all had it not been for the devotion of those who
had already recovered from the disease; it was known that no one ever caught the plague a second time. The same
applies, with rare exceptions, to many other diseases, such as smallpox, chicken pox, measles, and mumps. Yet
having had measles does not prevent a child from contracting chicken pox, or vice versa. The protection acquired by
experiencing one of these infections is specific for that infection; in other words, it is due to specific, acquired
immunity, also called adaptive immunity.

There are other infectious conditions, such as the common cold, influenza, pneumonia, and diarrheal diseases, that
can be caught again and again; these seem to contradict the notion of specific immunity. But the reason such
illnesses can recur is that many different infectious agents produce similar symptoms (and thus the same disease).
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For example, more than 100 viruses can cause the cluster of symptoms known as the common cold. Consequently,
even though infection with a particular agent does protect against reinfection by that same pathogen, it does not
confer protection from other pathogens that have not been encountered.

Acquired immunity is dependent on the specialized white blood cells known as lymphocytes. This section describes
the various ways in which lymphocytes operate to confer specific immunity. Although pioneer studies were begun in
the late 19th century, most of the knowledge of specific immunity has been gained since the 1960s, and new insights
are continually being obtained.

The nature of lymphocytes

General characteristics

Location in the lymphatic system

Lymphocytes are the cells responsible for the body’s ability to distinguish and react to an almost infinite number of
different foreign substances, including those of which microbes are composed. Lymphocytes are mainly a dormant
population, awaiting the appropriate signals to be stirred to action. The inactive lymphocytes are small, round cells
filled largely by a nucleus. Although they have only a small amount of cytoplasm compared with other cells, each
lymphocyte has sufficient cytoplasmic organelles (small functional units such as mitochondria, the endoplasmic
reticulum, and a Golgi apparatus) to keep the cell alive. Lymphocytes move only sluggishly on their own, but they
can travel swiftly around the body when carried along in the blood or lymph. At any one time an adult human has
approximately 2 × 1012 lymphocytes, about 1 percent of which are in the bloodstream. The majority are concentrated
in various tissues scattered throughout the body, particularly the bone marrow, spleen, thymus, lymph nodes, tonsils,
and lining of the intestines, which make up the lymphatic system. Organs or tissues containing such concentrations
of lymphocytes are termed lymphoid. The lymphocytes in lymphoid structures are free to move, although they are
not lying loose; rather, they are confined within a delicate network of lymph capillaries located in connective tissues
that channel the lymphocytes so that they come into contact with other cells, especially macrophages, that line the
meshes of the network. This ensures that the lymphocytes interact with each other and with foreign materials
trapped by the macrophages in an ordered manner.

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The human lymphatic system, showing the lymphatic vessels and lymphoid organs.

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T and B cells

Lymphocytes originate from stem cells in the bone marrow; these stem cells divide continuously, releasing
immature lymphocytes into the bloodstream. Some of these cells travel to the thymus, where they multiply and
differentiate into T lymphocytes, or T cells. The T stands for thymus-derived, referring to the fact that these cells
mature in the thymus. Once they have left the thymus, T cells enter the bloodstream and circulate to and within the
rest of the lymphoid organs, where they can multiply further in response to appropriate stimulation. About half of all
lymphocytes are T cells.

Some lymphocytes remain in the bone marrow, where they differentiate and then pass directly to the lymphoid
organs. They are termed B lymphocytes, or B cells, and they, like T cells, can mature and multiply further in the
lymphoid organs when suitably stimulated. Although it is appropriate to refer to them as B cells in humans and other
mammals, because they are bone-marrow derived, the B actually stands for the bursa of Fabricius, a lymphoid organ
found only in birds, the organisms in which B cells were first discovered.

B and T cells both recognize and help eliminate foreign molecules (antigens), such as those that are part of invading
organisms, but they do so in different ways. B cells secrete antibodies, proteins that bind to antigens. Since
antibodies circulate through the humours (i.e., body fluids), the protection afforded by B cells is called humoral
immunity. T cells, in contrast, do not produce antibodies but instead directly attack invaders. Because this second
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type of acquired immunity depends on the direct involvement of cells rather than antibodies, it is called cell-
mediated immunity. T cells recognize only infectious agents that have entered into cells of the body, whereas B cells
and antibodies interact with invaders that remain outside the body’s cells. These two types of specific, acquired
immunity, however, are not as distinct as might be inferred from this description, since T cells also play a major role
in regulating the function of B cells. In many cases an immune response involves both humoral and cell-mediated
assaults on the foreign substance. Furthermore, both classes of lymphocytes can activate or enhance a variety of
nonspecific immune responses.

Ability to recognize foreign molecules

Receptor molecules

Lymphocytes are distinguished from other cells by their capacity to recognize foreign molecules. Recognition is
accomplished by means of receptor molecules. A receptor molecule is a special protein whose shape is
complementary to a portion of a foreign molecule. This complementarity of shape allows the receptor and the
foreign molecule to conform to each other in a fashion roughly analogous to the way a key fits into a lock.

Receptor molecules are either attached to the surface of the lymphocyte or secreted into fluids of the body. B and T
lymphocytes both have receptor molecules on their cell surfaces, but only B cells manufacture and secrete large
numbers of unattached receptor molecules, called antibodies. Antibodies correspond in structure to the receptor
molecules on the surface of the B cell.

Antigens

Any foreign material—usually of a complex nature and often a protein—that binds specifically to a receptor
molecule made by lymphocytes is called an antigen. Antigens include molecules found on invading microorganisms,
such as viruses, bacteria, protozoans, and fungi, as well as molecules located on the surface of foreign substances,
such as pollen, dust, or transplanted tissue. When an antigen binds to a receptor molecule, it may or may not evoke
an immune response. Antigens that induce such a response are called immunogens. Thus, it can be said that all
immunogens are antigens, but not all antigens are immunogens. For example, a simple chemical group that can
combine with a lymphocyte receptor (i.e., is an antigen) but does not induce an immune response (i.e., is not an
immunogen) is called a hapten. Although haptens cannot evoke an immune response by themselves, they can
become immunogenic when joined to a larger, more complex molecule such as a protein, a feature that is useful in
the study of immune responses.

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Phagocytic cells destroy viral and bacterial antigens by eating them, while B cells produce …

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Many antigens have a variety of distinct three-dimensional patterns on different areas of their surfaces. Each pattern
is called an antigenic determinant, or epitope, and each epitope is capable of reacting with a different lymphocyte
receptor. Complex antigens present an “antigenic mosaic” and can evoke responses from a variety of specific
lymphocytes. Some antigenic determinants are better than others at effecting an immune response, presumably
because a greater number of responsive lymphocytes are present. It is possible for two or more different substances
to have an epitope in common. In these cases, immune components induced by one antigen are able to react with all
other antigens carrying the same epitope. Such antigens are known as cross-reacting antigens.

T cells and B cells differ in the form of the antigen they recognize, and this affects which antigens they can detect. B
cells bind to antigen on invaders that are found in circulation outside the cells of the body, while T cells detect only
invaders that have somehow entered the cells of the body. Thus foreign materials that have been ingested by cells of
the body or microorganisms such as viruses that penetrate cells and multiply within them are out of reach of
antibodies but can be eliminated by T cells.

Diversity of lymphocytes
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The specific immune system (in other words, the sum total of all the lymphocytes) can recognize virtually any
complex molecule that nature or science has devised. This remarkable ability results from the trillions of different
antigen receptors that are produced by the B and T lymphocytes. Each lymphocyte produces its own specific
receptor, which is structurally organized so that it responds to a different antigen. After a cell encounters an antigen
that it recognizes, it is stimulated to multiply, and the population of lymphocytes bearing that particular receptor
increases.

How is it that the body has such an incredible diversity of receptors that are always ready to respond to invading
molecules? To understand this, a quick review of genes and proteins will be helpful. Antigen receptor molecules are
proteins, which are composed of a few polypeptide chains (i.e., chains of amino acids linked together by chemical
bonds known as peptide bonds). The sequence in which the amino acids are assembled to form a particular
polypeptide chain is specified by a discrete region of DNA, called a gene. But, if every polypeptide region of every
antigen receptor were encoded by a different gene, the human genome (all the genetic information encoded in the
DNA that is carried on the chromosomes of cells) would need to devote trillions of genes to code just for these
immune system proteins. Since the entire human genome contains approximately 30,000 genes, individuals cannot
inherit a gene for each particular antigen receptor component. Instead, a mechanism exists that generates an
enormous variety of receptors from a limited number of genes.

What is inherited is a pool of gene segments for each type of polypeptide chain. As each lymphocyte matures, these
gene segments are pieced together to form one gene for each polypeptide that makes up a specific antigen receptor.
This rearrangement of alternative gene segments occurs predominantly, though not entirely, at random, so that an
enormous number of combinations can result. Additional diversity is generated from the imprecise recombination of
gene segments—a process called junctional diversification—through which the ends of the gene segments can be
shortened or lengthened. The genetic rearrangement takes place at the stage when the lymphocytes generated from
stem cells first become functional, so that each mature lymphocyte is able to make only one type of receptor. Thus,
from a pool of only hundreds of genes, an unlimited variety of diverse antigen receptors can be created.

Still other mechanisms contribute to receptor diversity. Superimposed on the mechanism outlined in simplified
terms above is another process, called somatic mutation. Mutation is the spontaneous occurrence of small changes in
the DNA during the process of cell division. It is called somatic when it takes place in body cells (Greek soma
means “body”) rather than in germ-line cells (eggs and sperm). Although somatic mutation can be a chance event in
any body cell, it occurs regularly in the DNA that codes for antigen receptors in lymphocytes. Thus, when a
lymphocyte is stimulated by an antigen to divide, new variants of its antigen receptor can be present on its
descendant cells, and some of these variants may provide an even better fit for the antigen that was responsible for
the original stimulation.

B-cell antigen receptors and antibodies

The antigen receptors on B lymphocytes are identical to the binding sites of antibodies that these lymphocytes
manufacture once stimulated, except that the receptor molecules have an extra tail that penetrates the cell membrane
and anchors them to the cell surface. Thus, a description of the structure and properties of antibodies, which are well
studied, will suffice for both.

Basic structure of the immunoglobulin molecule

Antibodies belong to the class of proteins called globulins, so named for their globular structure. Collectively,
antibodies are known as immunoglobulins (abbreviated Ig). All immunoglobulins have the same basic molecular
structure, consisting of four polypeptide chains. Two of the chains, which are identical in any given immunoglobulin
molecule, are heavy (H) chains; the other two are identical light (L) chains. The terms heavy and light simply mean
larger and smaller. Each chain is manufactured separately and is encoded by different genes. The four chains are
joined in the final immunoglobulin molecule to form a flexible Y shape, which is the simplest form an antibody can
take.

The four-chain structure of an antibody, or immunoglobulin, molecule

At the tip of each arm of the Y-shaped molecule is an area called the antigen-binding, or antibody-combining, site,
which is formed by a portion of the heavy and light chains. Every immunoglobulin molecule has at least two of
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these sites, which are identical to one another. The antigen-binding site is what allows the antibody to recognize a
specific part of the antigen (the epitope, or antigenic determinant). If the shape of the epitope corresponds to the
shape of the antigen-binding site, it can fit into the site—that is, be “recognized” by the antibody. Chemical bonds
called weak bonds then form to hold the antigen within the binding site.

The heavy and light chains that make up each arm of the antibody are composed of two regions, called constant (C)
and variable (V). These regions are distinguished on the basis of amino acid similarity—that is, constant regions
have essentially the same amino acid sequence in all antibody molecules of the same class (IgG, IgM, IgA, IgD, or
IgE), but the amino acid sequences of the variable regions differ quite a lot from antibody to antibody. This makes
sense, because the variable regions determine the unique shape of the antibody-binding site. The tail of the
molecule, which does not bind to antigens, is composed entirely of the constant regions of heavy chains.

The variable and constant regions of both the light and the heavy chains are structurally folded into functional units
called domains. Each light chain consists of one variable domain (VL) and one constant domain (CL). Each heavy
chain has one variable domain (VH) and three or four constant domains (CH1, CH2, CH3, CH4). Those domains that
make up the “tail” of the basic Y-shaped molecule (in other words, all the H-chain constant domains except CH1) are
responsible for the special biological properties of immunoglobulins—except, of course, for the capacity to bind to a
specific antigenic determinant. The tail of the antibody determines the fate of the antigen once it becomes bound to
the antibody.

Variable (V) and constant (C) domains within the light (L) and heavy (H) chains of an antibody, or …

The hinge region of the antibody is a short stretch of amino acids on the heavy chain located between the chain’s
CH1 and CH2 regions. It provides the molecule with flexibility, which is very useful in binding antigens. This
flexibility can actually improve the efficiency with which an antigen binds to the antibody. It can also help in cross-
linking antigens into a large lattice of antigen-antibody complexes, which are easily identified and destroyed by
macrophages.

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(A) The hinge region of an antibody molecule opens and closes to allow better binding between the …

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Classes of immunoglobulins

The term constant region is a bit misleading in that these segments are not identical in all immunoglobulins. Rather,
they are basically similar among broad groups. All immunoglobulins that have the same basic kinds of constant
domains in their H chains are said to belong to the same class. There are five main classes—IgG, IgM, IgA, IgD,
and IgE—some of which include a number of distinct subclasses. Each class has its own properties and functions
determined by the structural variations of the H chains. In addition, there are two basic kinds of L chains, called
lambda and kappa chains, either of which can be associated with any of the H chain classes, thereby increasing still
further the enormous diversity of immunoglobulins.

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The five main classes of antibodies (immunoglobulins): IgG, IgA, IgD, IgE, and IgM.

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IgG

IgG is the most common class of immunoglobulin. It is present in the largest amounts in blood and tissue fluids.
Each IgG molecule consists of the basic four-chain immunoglobulin structure—two identical H chains and two
identical L chains (either kappa or lambda)—and thus carries two identical antigen-binding sites. There are four
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subclasses of IgG, each with minor differences in its H chains but with distinct biological properties. IgG is the only
class of immunoglobulin capable of crossing the placenta; consequently, it provides some degree of immune
protection to the developing fetus. These molecules also are secreted into the mother’s milk and, once they have
been ingested by an infant, can be transported into the blood, where they confer immunity.

IgM

IgM is the first class of immunoglobulin made by B cells as they mature, and it is the form most commonly present
as the antigen receptor on the B-cell surface. When IgM is secreted from the cells, five of the basic Y-shaped units
become joined together to make a large pentamer molecule with 10 antigen-binding sites. This large antibody
molecule is particularly effective at attaching to antigenic determinants present on the outer coats of bacteria. When
this IgM attachment occurs, it causes microorganisms to agglutinate, or clump together.

IgA

IgA is the main class of antibody found in many body secretions, including tears, saliva, respiratory and intestinal
secretions, and colostrum (the first milk produced by lactating mothers). Very little IgA is present in the serum. IgA
is produced by B cells located in the mucous membranes of the body. Two molecules of IgA are joined together and
associated with a special protein that enables the newly formed IgA molecule to be secreted across epithelial cells
that line various ducts and organs. Although IgG is the most common class of immunoglobulin, more IgA is
synthesized by the body daily than any other class of antibody. However, IgA is not as stable as IgG, and therefore it
is present in lower amounts at any given time.

IgD

IgD molecules are present on the surface of most, but not all, B cells early in their development, but little IgD is ever
released into the circulation. It is not clear what function IgD performs, though it may play a role in determining
whether antigens activate the B cells.

IgE

IgE is made by a small proportion of B cells and is present in the blood in low concentrations. Each molecule of IgE
consists of one four-chain unit and so has two antigen-binding sites, like the IgG molecule; however, each of its H
chains has an extra constant domain (CH4), which confers on IgE the special property of binding to the surface of
basophils and mast cells. When antigens bind to these attached IgE molecules, the cell is stimulated to release
chemicals, such as histamines, that are involved in allergic reactions (see immune system disorder: Type I
hypersensitivity). IgE antibodies also help to protect against parasitic infections.

Normal production of antibody

Most individuals have fairly constant amounts of immunoglobulin in their blood, which represent the balance
between continuous breakdown of these proteins and their manufacture. There is about 4 times as much IgG
(including its subclasses) as IgA, 10 to 15 times as much as IgM, 300 times as much as IgD, and 30,000 times as
much as IgE.

Part of the normal production of immunoglobulin undoubtedly represents the response to antigenic stimulation that
happens continually, but even animals raised in surroundings completely free from microbes and their products
make substantial, though lesser, amounts of immunoglobulin. Much of the immunoglobulin therefore must represent
the product of all the B cells that are, so to speak, “ticking over” even if not specifically stimulated. It is therefore
not surprising that extremely sensitive methods can detect traces of antibodies that react with antigenic determinants
to which an animal has never been exposed but for which cells with receptors are present.

All B cells have the potential to use any one of the constant-region classes to make up the immunoglobulin they
secrete. As noted above, when first stimulated, most secrete IgM. Some continue to do so, but others later switch to
producing IgG, IgA, or IgE. Memory B cells, which are specialized for responding to repeat infections by a given
antigen, make IgG or IgA immediately (see Activation of T and B lymphocytes). What determines the balance
among the classes of antibodies is not fully understood. However, it is influenced by the nature and site of
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deposition of the antigen (for example, parasites tend to elicit IgE), and their production is clearly mediated by
factors, called cytokines, which are released locally by T cells.

T-cell antigen receptors

Structure of the T-cell receptor

T-cell antigen receptors are found only on the cell membrane. For this reason, T-cell receptors were difficult to
isolate in the laboratory and were not identified until 1983. T-cell receptors consist of two polypeptide chains. The
most common type of receptor is called alpha-beta because it is composed of two different chains, one called alpha
and the other beta. A less common type is the gamma-delta receptor, which contains a different set of chains, one
gamma and one delta. A typical T cell may have as many as 20,000 receptor molecules on its membrane surface, all
of either the alpha-beta or gamma-delta type.

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The basic structure of a typical T-cell antigen receptor.

The T-cell receptor molecule is embedded in the membrane of the cell, and a portion of the molecule extends away
from the cell surface into the area surrounding the cell. The chains each contain two folded domains, one constant
and one variable, an arrangement similar to that of the chains of antibody molecules. And, as is true of antibody
structure, the variable domains of the chains form an antigen-binding site. However, the T-cell receptor has only one
antigen-binding site, unlike the basic antibody molecule, which has two.

Many similarities exist between the structures of antibodies and those of T-cell receptors. Therefore, it is not
surprising that the organization of genes that encode the T-cell receptor chains is similar to that of immunoglobulin
genes. Similarities also exist between the mechanisms B cells use to generate antibody diversity and those used by T
cells to create T-cell diversity. These commonalities suggest that both systems evolved from a more primitive and
simpler recognition system (see Genetic origins of the immune system).

Function of the T-cell receptor

Despite the structural similarities, the receptors on T cells function differently from those on B cells. The functional
difference underlies the different roles played by B and T cells in the immune system. B cells secrete antibodies to
antigens in blood and other body fluids, but T cells cannot bind to free-floating antigens. Instead they bind to
fragments of foreign proteins that are displayed on the surface of body cells. Thus, once a virus succeeds in infecting
a cell, it is removed from the reach of circulating antibodies only to become susceptible to the defense system of the
T cell.

But how do fragments of a foreign substance come to be displayed on the surface of a body cell? First, the substance
must enter the cell, which can happen through either phagocytosis or infection. Next, the invader is partially
digested by the body cell, and one of its fragments is moved to the surface of the cell, where it becomes bound to a
cell-surface protein. This cell-surface protein is the product of one of a group of molecules encoded by the genes of
the major histocompatibility complex (MHC). In humans MHC proteins were first discovered on leukocytes (white
blood cells) and, therefore, are often referred to as HLA (human leukocyte antigens). (For information on the genetic
basis of the HLA, see genetics, human.) There are two major types of MHC molecules: class I molecules, which are
present on the surfaces of virtually all cells of the body that contain nuclei—that is, most body cells—and class II
molecules, which are restricted to the surfaces of most B cells and some T cells, macrophages, and macrophage-like
cells.

Two main types of mature T cells—cytotoxic T cells and helper T cells—are known. Some scientists hypothesize
the existence of a third type of mature T cell called regulatory T cells. Some T cells recognize class I MHC
molecules on the surface of cells; others bind to class II molecules. Cytotoxic T cells destroy body cells that pose a
threat to the individual—namely, cancer cells and cells containing harmful microorganisms. Helper T cells do not
directly kill other cells but instead help activate other white blood cells (lymphocytes and macrophages), primarily
by secreting a variety of cytokines that mediate changes in other cells. The function of regulatory T cells is poorly
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understood. To carry out their roles, helper T cells recognize foreign antigens in association with class II MHC
molecules on the surfaces of macrophages or B cells. Cytotoxic T cells and regulatory T cells generally recognize
target cells bearing antigens associated with class I molecules. Because they recognize the same class of MHC
molecule, cytotoxic and regulatory T cells are often grouped together; however, populations of both types of cells
associated with class II molecules have been reported. Cytotoxic T cells can bind to virtually any cell in the body
that has been invaded by a pathogen.

•
A cytotoxic T cell (left) recognizes antigens on the surface of a cell infected with a virus …

© C. Edelmann/Petit Format

T cells have another receptor, or coreceptor, on their surface that binds to the MHC molecule and provides
additional strength to the bond between the T cell and the target cell. Helper T cells display a coreceptor called CD4,
which binds to class II MHC molecules, and cytotoxic T cells have on their surfaces the coreceptor CD8, which
recognizes class I MHC molecules. These accessory receptors add strength to the bond between the T cell and the
target cell.

The T-cell receptor is associated with a group of molecules called the CD3 complex, or simply CD3, which is also
necessary for T-cell activation. These molecules are agents that help transduce, or convert, the extracellular binding
of the antigen and receptor into internal cellular signals; thus, they are called signal transducers. Similar signal
transducing molecules are associated with B-cell receptors.

Life cycle of T and B lymphocytes

T cells

When T-cell precursors leave the bone marrow on their way to mature in the thymus, they do not yet express
receptors for antigens and thus are indifferent to stimulation by them. Within the thymus the T cells multiply many
times as they pass through a meshwork of thymus cells. In the course of multiplication they acquire antigen
receptors and differentiate into helper or cytotoxic T cells. As mentioned in the previous section, these cell types,
similar in appearance, can be distinguished by their function and by the presence of the special surface proteins,
CD4 and CD8. Most T cells that multiply in the thymus also die there. This seems wasteful until it is remembered
that the random generation of different antigen receptors yields a large proportion of receptors that recognize self
antigens—i.e., molecules present on the body’s own constituents—and that mature lymphocytes with such receptors
would attack the body’s own tissues. Most such self-reactive T cells die before they leave the thymus, so that those
T cells that do emerge are the ones capable of recognizing foreign antigens. These travel via the blood to the
lymphoid tissues, where, if suitably stimulated, they can again multiply and take part in immune reactions. The
generation of T cells in the thymus is an ongoing process in young animals. In humans large numbers of T cells are
produced before birth, but production gradually slows down during adulthood and is much diminished in old age, by
which time the thymus has become small and partly atrophied. Cell-mediated immunity persists throughout life,
however, because some of the T cells that have emerged from the thymus continue to divide and function for a very
long time.

B cells

B-cell precursors are continuously generated in the bone marrow throughout life, but, as with T-cell generation, the
rate diminishes with age. Unless they are stimulated to mature (as described below), the majority of B cells also die,
although those that have matured can survive for a long time in the lymphoid tissues. Consequently, there is a
continuous supply of new B cells throughout life. Those with antigen receptors capable of recognizing self antigens
tend to be eliminated, though less effectively than are self-reactive T cells. As a result, some self-reactive cells are
always present in the B-cell population, along with the majority that recognize foreign antigens. The reason the self-
reactive B cells normally do no harm is explained in the following section.

Activation of T and B lymphocytes

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In its lifetime a lymphocyte may or may not come into contact with the antigen it is capable of recognizing, but if it
does it can be activated to multiply into a large number of identical cells, called a clone. Each member of the clone
carries the same antigen receptor and hence has the same antigen specificity as the original lymphocyte. The
process, called clonal selection, is one of the fundamental concepts of immunology.

Two types of cells are produced by clonal selection—effector cells and memory cells. Effector cells are the
relatively short-lived activated cells that defend the body in an immune response. Effector B cells are called plasma
cells and secrete antibodies, and activated T cells include cytotoxic T cells and helper T cells, which carry out cell-
mediated responses. The production of effector cells in response to first-time exposure to an antigen is called the
primary immune response. Memory cells also are produced at this time, but they do not become active at this point.
However, if the organism is reexposed to the same antigen that stimulated their formation, the body mounts a second
immune response that is led by these long-lasting memory cells, which then give rise to another population of
identical effector and memory cells. This secondary mechanism is known as immunological memory, and it is
responsible for the lifetime immunities to diseases such as measles that arise from childhood exposure to the
causative pathogen.

Activation of T cells

Helper-T-cell activation

Helper T cells do not directly kill infected cells, as cytotoxic T cells do. Instead they help activate cytotoxic T cells
and macrophages to attack infected cells, or they stimulate B cells to secrete antibodies. Helper T cells become
activated by interacting with antigen-presenting cells, such as macrophages. Antigen-presenting cells ingest a
microbe, partially degrade it, and export fragments of the microbe—i.e., antigens—to the cell surface, where they
are presented in association with class II MHC molecules. A receptor on the surface of the helper T cell then binds
to the MHC-antigen complex. But this event alone does not activate the helper T cell. Another signal is required,
and it is provided in one of two ways: either through stimulation by a cytokine or through a costimulatory reaction
between the signaling protein, B7, found on the surface of the antigen-presenting cell, and the receptor protein,
CD28, on the surface of the helper T cell. If the first signal and one of the second signals are received, the helper T
cell becomes activated to proliferate and to stimulate the appropriate immune cell. If only the first signal is received,
the T cell may be rendered anergic—that is, unable to respond to antigen.

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Stimulation of immune response by activated helper T cells

Encyclopædia Britannica, Inc.

A discussion of helper-T-cell activation is complicated by the fact that helper T cells are not a uniform group of cells
but rather can be divided into two general subpopulations—TH1 and TH2 cells—that have significantly different
chemistry and function. These populations can be distinguished by the cytokines they secrete. TH1 cells primarily
produce the cytokines gamma interferon, tumour necrosis factor-beta, and interleukin-2 (IL-2), while TH2 cells
mainly synthesize the interleukins IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13. The main role of the TH1 cells is to
stimulate cell-mediated responses (those involving cytotoxic T cells and macrophages), while TH2 cells primarily
assist in stimulating B cells to make antibodies.

Once the initial steps of activation have occurred, helper T cells synthesize other proteins, such as signaling proteins
and the cell-surface receptors to which the signaling proteins bind. These signaling molecules play a critical role not
only in activating the particular helper T cell but also in determining the ultimate functional role and final
differentiation state of that cell. For example, the helper T cell produces and displays IL-2 receptors on its surface
and also secretes IL-2 molecules, which bind to these receptors and stimulate the helper T cell to grow and divide.

Results of helper-T-cell activation

The overall result of helper-T-cell activation is an increase in the number of helper T cells that recognize a specific
foreign antigen, and several T-cell cytokines are produced. The cytokines have other consequences, one of which is
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that IL-2 allows cytotoxic or regulatory T cells that recognize the same antigen to become activated and to multiply.
Cytotoxic T cells, in turn, can attack and kill other cells that express the foreign antigen in association with class I
MHC molecules, which—as explained above—are present on almost all cells. So, for example, cytotoxic T cells can
attack target cells that express antigens made by viruses or bacteria growing within them (see Cell-mediated immune
mechanisms). Regulatory T cells may be similar to cytotoxic T cells, but they are detected by their ability to
suppress the action of B cells or even of helper T cells (perhaps by killing them). Regulatory T cells thus act to damp
down the immune response and can sometimes predominate so as to suppress it completely.

Activation of B cells

A B cell becomes activated when its receptor recognizes an antigen and binds to it. In most cases, however, B-cell
activation is dependent on a second factor mentioned above—stimulation by an activated helper T cell. Once a
helper T cell has been activated by an antigen, it becomes capable of activating a B cell that has already encountered
the same antigen. Activation is carried out through a cell-to-cell interaction that occurs between a protein called the
CD40 ligand, which appears on the surface of the activated helper T cells, and the CD40 protein on the B-cell
surface. The helper T cell also secretes cytokines, which can interact with the B cell and provide additional
stimulation. Antigens that induce a response in this manner, which is the typical method of B-cell activation, are
called T-dependent antigens.

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Clonal selection of a B cell

Encyclopædia Britannica, Inc.

Most antigens are T-dependent. Some, however, are able to stimulate B cells without the help of T cells. The T-
independent antigens are usually large polymers with repeating, identical antigenic determinants. Such polymers
often make up the outer coats and long, tail-like flagella of bacteria. Immunologists think that the enormous
concentration of identical T-independent antigens creates a strong enough stimulus without requiring additional
stimulation from helper T cells.

Interaction with antigens causes B cells to multiply into clones of immunoglobulin-secreting cells. Then the B cells
are stimulated by various cytokines to develop into the antibody-producing cells called plasma cells. Each plasma
cell can secrete several thousand molecules of immunoglobulin every minute and continue to do so for several days.
A large amount of that particular antibody is released into the circulation. The initial burst of antibody production
gradually decreases as the stimulus is removed (e.g., by recovery from infection), but some antibody continues to be
present for several months afterward.

The process just described takes place among the circulating B lymphocytes. The B cells that are called memory
cells, however, encounter antigen in the germinal centres—compartments in the lymphoid tissues where few T cells
are present—and are activated in a different way. Memory cells, especially those with the most effective receptors,
multiply extensively, but they do not secrete antibody. Instead, they remain in the tissues and the circulation for
many months or even years. If, with the help of T cells, memory B cells encounter the activating antigen again, these
B cells rapidly respond by dividing to form both activated cells that manufacture and release their specific antibody
and another group of memory cells. The first group of memory cells behaves as though it “remembers” the initial
contact with the antigen. So, for example, if the antigen is microbial and an individual is reinfected by the microbe,
the memory cells trigger a rapid rise in the level of protective antibodies and thus prevent the associated illness from
taking hold.

Antibody-mediated immune mechanisms

Protective attachment to antigens

Many pathogenic microorganisms and toxins can be rendered harmless by the simple attachment of antibodies. For
example, some harmful bacteria, such as those that cause diphtheria and tetanus, release toxins that poison essential
body cells. Antibodies, especially IgG, that combine with such toxins neutralize them. Also susceptible to simple
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antibody attachment are the many infectious microbes—including all viruses and some bacteria and protozoans—
that live within the body cells. These pathogens bear special molecules that they use to attach themselves to the host
cells so that they can penetrate and invade them. Antibodies can bind to these molecules to prevent invasion.
Antibody attachment also can immobilize bacteria and protozoans that swim by means of whiplike flagella. In these
instances antibodies protect simply by combining with the repeating protein units that make up these structures,
although they do not kill or dispose of the microbes. The actual destruction of microbes involves phagocytosis by
granulocytes and macrophages, and this is greatly facilitated by the participation of the complement system.

Activation of the complement system

Complement is a term used to denote a group of more than 30 proteins that act in concert to enhance the actions of
other defense mechanisms of the body. Complement proteins are produced by liver cells and, in many tissues, by
macrophages. Most of these proteins circulate in the blood and other body fluids in an inactive form. They become
activated in sequential fashion; once the first protein in the pathway is turned on, the following complement proteins
are called into action, with each protein turning on the next one in line.

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Pathways of complement activation

Encyclopædia Britannica, Inc.

The action of complement is nonspecific—i.e., complement proteins are not recognized by and do not interact with
antigen-binding sites. In fact, complement proteins probably evolved before antibodies. Complement functions are
similar among many species, and corresponding components from one species can carry out the same functions
when introduced into another species. The complement system is ingenious in providing a way for antibodies,
whatever their specificity, to produce the same biological effects when they combine with antigens.

Originally immunologists thought that the complement system was initiated only by antigen-antibody complexes,
but later evidence showed that other substances, such as the surface components of a microorganism alone, could
trigger complement activation. Thus, there are two complement activation pathways: the first one to be discovered,
the classical pathway, which is initiated by antigen-antibody complexes; and the alternative pathway, which is
triggered by other means, including invading pathogens or tumour cells. (The term alternative is something of a
misnomer because this pathway almost certainly evolved before the classical pathway. The terminology reflects the
order of discovery, not the evolutionary age of the pathways.) The classical and alternative pathways are composed
of different proteins in the first part of their cascades, but eventually both pathways converge to activate the same
complement components, which destroy and eliminate invading pathogens.

The classical complement pathway is activated most effectively by IgM and the most abundant of the
immunoglobulins, IgG. But, for activation to occur, antibodies must be bound to antigens (the antigen-antibody
complex mentioned above). Free antibodies do not activate complement. To initiate the cascade, the first
complement protein in the pathway, C1, must interact with a bound immunoglobulin. Specifically, C1 interacts with
the tail of the Y portion of the bound antibody molecule—i.e., the nonspecific part of the antibody that does not bind
antigen. Once bound to the antibody, C1 is cleaved, a process that activates C1 and allows it to split and activate the
next complement component in the series. This process is repeated on the following proteins in the pathway until the
complement protein C3—the most abundant and biologically the most important component of the complement
system—is activated. The classical and alternative complement pathways converge here, at the cleavage of the C3
molecule, which, once split, produces C3a and the large active form of C3, the fragment called C3b.

C3b carries out several functions:

1. It brings about lysis (bursting) of the target cell by activating subsequent steps in the cascade, leading to the
formation of a ringlike structure called the membrane attack complex. This structure, which is composed of
complement proteins C5 through C9, inserts itself into the membrane of the invading pathogen and creates
a hole through which the cell contents leak out, killing the cell.
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2. C3b can combine with another protein that converts more C3 protein to C3b.

3. C3b can initiate the alternative pathway of complement activation.

4. But perhaps the most important result of C3b production is that great numbers of C3b molecules are
deposited on the surface of an invading pathogen in a process called opsonization. This makes the
microorganism more attractive to phagocytic cells such as macrophages and neutrophils. The attraction
occurs because receptors on the surface of phagocytes recognize and bind to the C3b molecule on the
surface of the pathogen, stimulating phagocytosis. The microbe is then killed by digestive enzymes present
in the phagocytes. If microbes are not immediately killed and are able to reach the bloodstream or the liver,
spleen, or bone marrow, they can become coated with antibody and complement there and be ingested by
phagocytes.

The small protein fragments that are released during the activation of complement are potent pharmacological agents
that help promote an inflammatory response by causing mast cells and basophils to release histamine, which
increases the permeability of blood vessels, and by attracting granulocytes and monocytes.

Thus, when a microbe penetrates the body, if antibodies reactive with its surface are already present (or if the
microorganism activates complement without the help of antibodies, through the alternative complement pathway),
the complete complement sequence may be activated and the microbe killed by damage to its outer membrane. This
mechanism is effective only with bacteria that lack protective coats and with certain large viruses, but it is
nevertheless important. Persons who lack C3 and thus cannot complete the later steps in the complement sequence
are vulnerable to repeated bacterial infections.

Clearly such a biologically important chain of reactions could do more harm than good if its effects were to spread
beyond the site of antigen invasion. Fortunately, the active intermediates at each stage in the complement sequence
become rapidly inactivated or destroyed by inhibitors if they fail to initiate the next step. With rare exceptions, this
confines the activation to the place in the body where it is needed.

Activation of killer cells

Some cells that bear antigen-antibody complexes do not attract complement; their antibody molecules are far apart
on the cell surface or are of a class that does not readily activate the complement system (e.g., IgA, IgD, and IgE).
Other cells have outer membranes that are so tough or can be repaired so quickly that the cells are impermeable to
activated complement. Still others are so large that phagocytes cannot ingest them. Such cells, however, can be
attacked by killer cells present in the blood and lymphoid tissues. Killer cells, which may be either cytotoxic T cells
or natural killer cells, have receptors that bind to the tail portion of the IgG antibody molecule (the part that does not
bind to antigen). Once bound, killer cells insert a protein called perforin into the target cell, causing it to swell and
burst. Killer cells do not harm bacteria, but they play a role in destroying body cells infected by viruses and some
parasites.

Other antibody-mediated mechanisms

The protection conferred by IgA antibodies, which are transported to the surface of mucous-membrane-lined
passages, is somewhat different. Complement activation is not involved; there are no complement proteins in the
lining of the gut or the respiratory tract. Here the available immune defense mechanism is primarily the action of
IgA combining with microbes to prevent them from entering the cells of the lining. The bound microbes are then
swept out of the body. IgA also appears to direct certain types of cell-mediated killing.

IgE antibodies also invoke unique mechanisms. As stated earlier, most IgE molecules are bound to special receptors
on mast cells and basophils. When antigens bind to IgE antibodies on these cells, the interaction does not cause
ingestion of the antigens but rather triggers the release of pharmacologically active chemical contents of the cells’
granules. The chemicals released cause a sudden increase in permeability of the local blood vessels, the adhesion
and activation of platelets (blood cell fragments that trigger clotting), which release their own active agents, the
contraction of smooth muscle in the gut or in the respiratory tubes, and the secretion of fluids—all of which tend to
dislodge large multicellular parasites such as hookworms. Eosinophil granulocytes and IgE together are particularly
effective at destroying parasites such as the flatworms that cause schistosomiasis. The eosinophils plaster themselves
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to the worms bound to IgE and release chemicals from their granules that break down the parasite’s tough,
protective skin. Therefore, IgE antibodies—although they can be a nuisance when they react with otherwise
harmless antigens, as discussed in immune system disorder: Type I hypersensitivity—appear to have a special
protective role against the larger parasites.

Transfer of antibodies from mother to offspring

A newborn mammal has no opportunity to develop protective antibodies on its own, unless, as happens very rarely,
it was infected while in the uterus. Yet it is born into an environment similar to its mother’s, which contains all the
potential microbial invaders to which she is exposed. Although the fetus possesses the components of innate
immunity, it has few or none of its mother’s lymphocytes. The placenta generally prevents the maternal
lymphocytes from crossing into the uterus, where they would recognize the fetal tissues as foreign antigens and
cause a reaction similar to the rejection of an incompatible organ transplant.

What is transferred across the placenta in many species is a fair sample of the mother’s antibodies. How this
happens depends on the structure of the placenta, which varies among species. In humans maternal IgG antibodies—
but not those of the other immunoglobulin classes—are transported across the placenta into the fetal bloodstream
throughout the second two-thirds of pregnancy. In many rodents a similar transfer occurs, but primarily across the
yolk sac.

In horses and cattle, which have more layers of cells in their placentas, no antibodies are transferred during fetal life,
and the newborn arrives into the world with no components of specific immunity. There is, however, a second
mechanism that makes up for this deficiency. The early milk (colostrum) is very rich in antibodies—mainly IgA but
also some IgM and IgG—and during the first few days of life the newborn mammal can absorb these proteins intact
from the digestive tract directly into the bloodstream. Drinking colostrum is therefore essential for newborn horses
and cattle and required to a somewhat lesser extent by other mammals. The capacity of the digestive tract to absorb
intact proteins must not last beyond one or two weeks, since once foods other than milk are ingested the proteins and
other antigens in them would also be absorbed intact and could act as immunogens to which the growing animal
would become allergic (see immune system disorder: Allergies). IgA in milk is, however, rather resistant to
digestion and can function within the gut even after intact absorption into the bloodstream has ended. Human
colostrum is also rich in IgA, with the concentration highest immediately after birth.

After a newborn has received its supply of maternal antibodies, it is as fully protected as its mother. This means, of
course, that if the mother has not developed immunity to a particular pathogen, the newborn will likewise be
unprotected. For this reason, a physician may recommend that a prospective mother receive immunizations against
tetanus and certain other disorders. (The active immunization of pregnant women against certain viral diseases, such
as rubella [German measles], must be avoided, however, because the immunizing agent can cross the placenta and
produce severe fetal complications.)

As important as the passively transferred maternal antibodies are, their effects are only temporary. The maternal
antibodies in the blood become diluted as the animal grows; moreover, they gradually succumb to normal metabolic
breakdown. Because the active development of acquired immunity is a slow and gradual process, young mammals
actually become more susceptible to infection during their early stages of growth than they are immediately after
birth.

Occasionally the transfer of maternal antibodies during fetal life can have harmful consequences. A well-known
example of this is erythroblastosis fetalis, or hemolytic disease of the newborn, a disorder in which maternal
antibodies destroy the child’s red blood cells during late pregnancy and shortly after birth. The most severe form of
erythroblastosis fetalis is Rh hemolytic disease, which develops when:

1. The fetus is Rh-positive; that is, its red blood cells carry an antigen known as the Rh factor.

2. The mother is Rh-negative, which is to say her red blood cells lack the Rh factor.

3. The mother’s immune system has been previously activated against the Rh antigen; this usually is the result
of exposure to fetal cells during the birth of an earlier Rh-positive baby or a transfusion of Rh-positive
blood.
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Rh hemolytic disease can be prevented by giving the mother injections of anti-Rh antibody shortly after the birth of
an Rh-positive child. This antibody destroys any Rh-positive fetal cells in the maternal circulation, thereby
preventing the activation of the mother’s immune system should she conceive another Rh-positive fetus.

Cell-mediated immune mechanisms

In addition to their importance in cooperating with B cells that secrete specific antibodies, T cells have important,
separate roles in protecting against antigens that have escaped or bypassed antibody defenses. Immunologists have
long recognized that antibodies do not necessarily protect against viral infections, because many viruses can spread
directly from cell to cell and thus avoid encountering antibodies in the bloodstream. It is also known that persons
who fail to make antibodies are very susceptible to bacterial infections but are not unduly liable to viral infections.
Protection in these cases results from cell-mediated immunity, which destroys and disposes of body cells in which
viruses or other intracellular parasites (such as the bacteria that cause tuberculosis and leprosy) are actively growing,
thus depriving microorganisms of their place to grow and exposing them to antibodies.

As discussed in the section Activation of T and B lymphocytes, cell-mediated immunity has two mechanisms. One
involves activated helper T cells, which release cytokines. In particular, the gamma interferon produced by helper T
cells greatly increases the ability of macrophages to kill ingested microbes; this can tip the balance against microbes
that otherwise resist killing. Gamma interferon also stimulates natural killer cells. The second mechanism of cell-
mediated immunity involves cytotoxic T cells. They attach themselves by their receptors to target cells whose
surface expresses appropriate antigens (notably ones made by developing viruses) and damage the infected cells
enough to kill them.

Cytotoxic T cells may kill infected cells in a number of ways. The mechanism of killing used by a given cytotoxic T
cell depends mainly on a number of costimulatory signals. In short, cytotoxic T cells can kill their target cells either
through the use of pore-forming molecules, such as perforins and various components of cytoplasmic granules, or by
triggering a series of events with the target cell that activate a cell death program, a process called apoptosis. In
general, the granular cytotoxic T cells tend to kill cells directly by releasing the potent contents of their cytotoxic
granules at the site of cell-to-cell contact. This renders the cell membrane of the target cell permeable, which allows
the cellular contents to leak out and the cell to die. The nongranular cytotoxic T cells often kill cells by inducing
apoptosis, usually through the activation of a cell-surface protein called Fas. When a protein on the surface of the
cytotoxic T cell interacts with the Fas protein on the target cell, Fas is activated and sends a signal to the nucleus of
the target cell, thus initiating the cell death process. The target cell essentially commits suicide, thereby destroying
the virus within the cell as well.

Immunity against cancer

Cancer cells are normal body cells that have been altered in a manner that allows them to divide relentlessly,
ignoring normal signals of restraint. As a result, cancer cells form clusters of cells, called tumours, that invade and
colonize tissues, eventually undermining organ function and causing death. In the early 20th century the pioneering
immunologist Paul Ehrlich pointed out that the enormous multiplication and differentiation of cells during prenatal
life must afford many opportunities for aberrant cells to appear and grow but that immune mechanisms eliminate
such cells. The idea that such a mechanism continues to function throughout life, weeding out newly arisen cancer
cells, became popular in the 1950s and ’60s when a number of immunologists postulated immune surveillance, the
theory that T-cell-mediated immunity evolved as a specific defense against cancer cells and that T cells constantly
patrol the body, searching for abnormal body cells that carry antigens on their surface which are not found on
healthy body cells. Although it has its compelling aspects, the immunosurveillance theory remains just a theory, and
a controversial one at that.

The role of the immune system in protecting against cancer has not been fully explained, but nevertheless there is no
question that in some instances the immune system can distinguish cancer cells from normal cells. The study of
tumour immunology has shown unequivocally that cancer cells do carry antigens that are not present on healthy
cells. Immunologists distinguish broadly between two types of tumour antigens: tumour-specific antigens, which are
found only on cancer cells and not on their normal counterparts, and tumour-associated antigens, which are found on
both normal and cancer cells but which are abnormally expressed—e.g., are overproduced—on cancer cells. In both
cases these antigens have been shown to evoke an immune response, although not necessarily one strong enough to
eliminate the tumour.
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Why does a tumour continue to grow if an immune response against it is induced? Through animal experiments, a
number of mechanisms have been identified that allow tumours to avoid recognition and destruction by the immune
system:

1. The surfaces of cancer cells may lose antigens that are recognizable by the immune system.

2. Cancer cells may lose all class I MHC molecules from their surface, which prevents cytotoxic T cells from
recognizing the cells.

3. Some cancer cells produce immunosuppressive chemicals that can inhibit T cells directly or that can
activate regulatory T cells.

4. Some cancer cells shed some of their antigens, and these newly released, free-floating antigens may bind to
the receptors on cytotoxic T cells, plugging them up so that the T cells cannot bind to the cancer cells and
eliminate them.

5. Certain cancer cells can outmaneuver an immune response by growing so rapidly or becoming such a dense
mass that immune cells cannot come in contact with most of them.

Other dysfunctions of the immune system, such as immune suppression and immune deficiency, may contribute to
cancer development and growth. Individuals such as transplant patients who have been treated with
immunosuppressive drugs for a long period of time are more likely to develop certain types of cancer, as are patients
with immunodeficiency diseases. For example, people with AIDS (acquired immunodeficiency syndrome) are more
prone to developing cancers associated with viruses, such as Kaposi sarcoma. The incidence of cancer also increases
greatly in old age, when some immune responses decline. But defective immune responses may not be the major
factor involved in cancer development in the elderly, since genetic mutations that are linked to cancer also
accumulate with age.

Much research has been devoted to developing effective immunotherapies against cancer, but the effectiveness of
this approach has been marginal. Nevertheless, researchers continue to pursue immunotherapeutic approaches. One
avenue of research has focused on finding ways to immunize patients against the specific cancer growing within
them. This approach targets tumour-specific antigens found on the cancer cells. Because these antigens are altered
forms of normal self antigens, they are “foreign” and could be recognized by the immune system as such, but often
they are not. However, investigators are working to develop vaccines that stimulate an immune response to these
antigens, hoping that the reaction would be strong enough to eliminate the cancer.

Prophylactic immunization

Prophylactic immunization refers to the artificial establishment of specific immunity, a technique that has
significantly reduced suffering and death from a variety of infectious diseases. There are two types of prophylactic
immunization: passive immunization, in which protection is conferred by introducing preformed antibodies or
lymphocytes from another individual whose immune system was stimulated by the appropriate antigen, and active
immunization, in which protection results from the administration of a vaccine, with dead or harmless living forms
of an organism or with an inactivated toxin, that stimulates the immune system to produce lymphocytes and
antibodies against that organism or toxin.

Passive immunization

It is sometimes the case that an infectious organism or a poisonous substance can have such a rapid deleterious
effect that the victim does not have time to develop an immune response spontaneously. At such times passive
immunization with preformed antibodies can provide life-saving assistance in combating the pathogen or poison.
This situation may arise in victims of poisonous snakebites or botulism, as well as in those in whom such infections
as diphtheria, tetanus, or gas gangrene have progressed to the point at which bacterial toxins have been absorbed
into the bloodstream. It is also the case with bites from a rabid animal, although active immunization is begun at the
same time, since the spread of the rabies infection to the central nervous system is relatively slow. Physicians use
passive immunization as temporary protection for persons traveling to countries where hepatitis B is prevalent.
Passive immunization provides antibodies to persons who suffer from B-cell deficiencies and are therefore unable to
 94

make antibodies for themselves (see immune system disorder: Immune deficiencies). Also, as discussed earlier,
passive immunizations of anti-Rh antibody can prevent erythroblastosis fetalis.

Protective immunoglobulins—primarily of the IgG class—can be prepared from the blood of humans or other
species (e.g., horses or rabbits) that have already developed specific immunity against the relevant antigens. These
preparations are known as antiserums. (This explains the original term for passive immunization, which is serum
therapy.) Human IgG is slowly broken down in the recipient’s body, the concentration falling by about one-half
every three weeks, so that effective amounts of antibody can be present for two or three months. Human antiserum is
used whenever it is available, because IgG from other species is far more likely to provoke an immune response that
will eliminate the antibody and may lead to serum sickness (see immune system disorder: Type III hypersensitivity).

Active immunization

Active immunization aims to ensure that a sufficient supply of antibodies or T and B cells that react against a
potential infectious agent or toxin are present in the body before infection occurs or the toxin is encountered. Once it
has been primed, the immune system either can prevent the pathogen from establishing itself or can rapidly mobilize
the various protective mechanisms described above to abort the infection or toxin in its earliest stages.

The vaccines used to provide active immunization need not contain living microbes. What matters is that they
include the antigens important in evoking a protective response and that those antigens be administered in a
harmless form sufficient in amount and persistence to produce an immune response similar to the natural infection.
Bacterial toxins, such as those that cause tetanus or diphtheria, can be rendered harmless by treatment with
formaldehyde without affecting their ability to act as immunogens. These modified toxins, or toxoids, usually are
adsorbed onto an inorganic gel before being administered, an approach that increases the likelihood that the toxoid
will be retained in a macrophage. Toxoids elicit effective, long-lasting immunity against bacterial toxins. When
immunization against several antigenic determinants is desired or the important antigenic component is not known,
it may be prudent to use the entire microbe, which has been killed in a manner that does not alter it significantly.
Such so-called “killed” vaccines are used to immunize against typhoid, pertussis (whooping cough), plague, and
influenza, for example. In other cases, researchers have developed attenuated (i.e., weakened) strains of bacteria or
viruses. Attenuated vaccines cause an infection but do not produce the full array of signs and symptoms of the
disease, because the infectious agent multiplies to only a limited extent in the body and never reverts to the virulent
form. The use of such live microbes provides the most effective prophylaxis of all, since they truly imitate a mild
form of the natural infection. Such are the vaccines for yellow fever, poliomyelitis (oral vaccine), measles, rubella,
and tuberculosis. Although sufficiently attenuated as far as healthy persons are concerned, live vaccines may cause
the full disease in persons who have an immune deficiency.

Most vaccines are administered by injection, but a few are given orally. Ultimately mucosal vaccines (those
administered to mucosal surfaces such as those lining the gut, nasal passages, or the urogenital tract) may be the
most effective vaccines available because of their unique ability to stimulate IgA responses and because of their ease
of administration. Recombinant DNA technology has allowed researchers to use modified bacteria and viruses that
are not harmful to humans to immunize individuals against an antigen from a pathogenic microorganism. This
approach involves introducing into the DNA of the harmless microorganism a gene from a pathogenic organism that
encodes an antigen capable of eliciting a protective immune response but not the full-blown disease. Once
inoculated into the host, the microorganism generates the protective antigen of the pathogen and immunizes the host.
An effective oral vaccine against cholera was developed based on this approach.

Sometimes different strains of a microorganism, each characterized by a different antigenic determinant, give rise to
the same disease. In such cases neither natural infection nor prophylactic immunization with any one strain protects
against infection by the others. For example, a variety of virus strains cause the common cold, but it is impractical to
immunize against each strain. On the other hand, although there are more than 60 different strains of pneumococci
that can cause bacterial pneumonia, some strains are much more common than others. Consequently a vaccine
containing antigens from up to 14 of the most common strains is useful in protecting persons at special risk.

Active immunization is often the most effective and least costly method of protecting against an infectious disease.
Vaccination campaigns against many diseases, such as diphtheria, polio, and measles, have been tremendously
successful. In cases in which 95 percent or more of the population at risk is protected and humans are the only
 95

reservoir of infection, active immunization can lead to the worldwide eradication of the infectious agent, as has been
achieved in the case of smallpox.

Evolution of the immune system

Related Topics
• bone marrow

• white blood cell

• lymph

• lymphoid tissue

• mast cell

• phagocytosis

• mononuclear phagocyte system

• immune system disorder

• Bruce A. Beutler

• Ralph M. Steinman

Virtually all organisms have at least one form of defense that helps repel disease-causing organisms. Advanced
vertebrate animals, a group that includes humans, defend themselves against such microorganisms by means of a
complex group of defense responses collectively called the immune system. This protective system evolved from
simpler defense mechanisms, but the evolutionary twists and turns that led to its development are not entirely clear.
To unravel the path that the vertebrate immune system followed in its evolution, investigators have studied the
defense responses of various living organisms. They also have examined the genes of immune system proteins for
clues to the genetic origins of immunity. These approaches and the information they have yielded are discussed in
the following sections. A discussion of human immune diseases is provided in the article immune system disorder.

The development of immunity in major animal groups

Because the immune system is composed of cells and tissues that do not lend themselves to fossilization, it is
impossible to trace the evolution of immunity from the paleontological record. But, because all animals exhibit some
general ability to recognize self and to repel foreign substances, it is possible to study the immune capacity of living
animals and, based on the relative positions of these animals in the evolutionary tree, to extrapolate a reasonable
evolutionary history of the immune system.

Immune capacity among invertebrates

From the lowliest protozoans to the higher marine tunicates, invertebrates have means of distinguishing self
components from nonself components. Sponges from one colony will reject tissue grafts from a different colony but
will accept grafts from their own. When tissue grafts are made in animals higher up the evolutionary tree—between
individual annelid worms or starfish, for example—the foreign tissue is commonly invaded by phagocytic cells
(cells that engulf and destroy foreign material) and cells resembling lymphocytes (white blood cells of the immune
system), and it is destroyed. Yet tissues grafted from one part of the body to another on the same individual adhere
and heal readily and remain healthy. So it seems that something akin to cellular immunity is present at this level of
evolution.

Similar Topics
 96

• endocrine system

• human ear

• photophore

• mesentery

• stomach

• heart

• gonad

• intestine

• gland

• brain

Insects engulf and eliminate foreign invaders through the process of phagocytosis (“cellular eating”). They have
factors present in their circulatory fluids that can bind to foreign cells and cause clumping, or agglutination, of a
number of these cells, an event that facilitates phagocytosis. Insects also seem to acquire immunity to infectious
agents.

Immune capacity among vertebrates

The most sophisticated immune systems are those of the vertebrates. Recognizable lymphocytes and
immunoglobulins (Ig; also called antibodies) appear only in these organisms. The most primitive living
vertebrates—the jawless fishes (hagfish and lampreys)—do not have lymphoid tissues corresponding to a spleen or a
thymus, and their immune responses, although demonstrable, are very weak and sluggish. Farther up the
evolutionary tree, at the level of the cartilaginous fishes (sharks and rays) and the bony fishes, a thymus and a spleen
are present, as are immunoglobulins, although only those immunoglobulins of the IgM class are detectable. Fish lack
specialized lymph nodes, but they do have clusters of lymphocytes in the gut that may serve an analogous purpose.

It is not until the level of the terrestrial vertebrates—amphibians, reptiles, birds, and mammals—that a complete
immune system with thymus, spleen, bone marrow, and lymph nodes is present and IgM and IgG antibodies are
made. Antibodies of the IgA class are found only in birds and mammals, and IgE antibodies are confined to
mammals. So it appears that the most primitive devices for producing specific, acquired immunity gradually
diversified to meet the new environmental hazards as animals moved out of the sea onto the land.

The evolution of the complement system (a group of proteins involved in immune responses) may have occurred
faster than that of the immunoglobulin system. The jawless fishes have complement components corresponding only
to the later-acting (i.e., cytolytic, or cell-killing) aspects of complement function, but all higher vertebrates have
components similar to the complete complement system of mammals. The fact that the complement system has been
so well conserved during evolution implies not only that it has been of great biological value but also that
complement and immunoglobulins have interacted throughout the evolution of the immune system in higher
vertebrates. (For more information on the complement system, see Antibody-mediated immune mechanisms.)

Genetic origins of the immune system

Researchers have found many similarities between the structures of proteins involved in antigen recognition and
those in cell-to-cell recognition in the immune system. (Antigens are the foreign proteins that antibodies recognize
 97

and bind to.) These proteins include the antigen receptors of lymphocytes, the (MHC) proteins, the coreceptors
involved in cell-to-cell recognition in immune reactions (such as the receptors named CD4, CD8, and CD28), and
the FC receptor that binds to the stem of the Y-shaped immunoglobulin molecule. A number of proteins not involved
in the immune system also share structural features with these proteins. The main feature similarity is a structure
called the immunoglobulin domain. Each protein is composed of one or more Ig domains of nearly identical size.
The domains are formed into a loop by bonds between sulfur atoms on the amino acids at the ends. Although each
domain is different and serves a different function in the molecule as a whole, the number and order of the amino
acids forming each domain are far more similar than would be expected if each had arisen independently in the
course of evolution. Equally remarkable is the fact that nerve cells, thymus cells, and T lymphocytes in mice and
rats carry a surface protein termed Thy-1 (thymus-1 antigen), the function of which is unknown, that also has this
same basic structure and a similar arrangement of amino acids. The similarities suggest that the genes for all these
molecules originated from some primitive gene involved in the recognition of one cell by another, which is required
for orderly development of a complex, multicellular organism, and that during evolution they had acquired different
functions. Researchers named this group of genes and their protein products the immunoglobulin superfamily. The
processes whereby one ancestral gene could have given rise to such a family of genes include gene duplication,
crossing over, and mutation, all of which are discussed in detail in genetics.

Not surprisingly, molecules that have a similar function in different species (e.g., immunoglobulins or MHC
components) show an even closer resemblance. By analyzing the number of differences in the amino acids and their
position in the polypeptide chains that make up IgM and IgG molecules in, for example, humans, mice, and rabbits
and by making reasonable assumptions about mutation rates, scientists can estimate roughly how many generations
would have had to elapse—and hence how much time—for the present immunoglobulins of these species to have
evolved from a common ancestral IgM-like molecule. Such calculations suggest that divergence from the ancestral
immunoglobulin took place some 200 million years ago. That was about the same time amphibians are thought to
have diverged from the main vertebrate line. So one may conclude that a functional immune system arose even
earlier and has continued to provide a defense against foreign agents ever since.
Samuel Scott PerdueJohn H. Humphrey

MEDICINE CABINET (TERMINOLOGY FOR DRUGS)

Brands are the proprietary names and trademarks of the pharmaceutical companies that make and distribute them.
Names in parentheses are generic or chemical names. You may see either or both on labels of your medicines. With
some exceptions, the medications presented require a prescription. Only selected drug categories are presented with
examples. If you wish more information on selected drugs, click on the drug Category name. To return to the main
listing, close the category pop-up box.

This content is for educational information only. Ask your physician or pharmacist any questions you may have
about taking your medications.
Category What I call then They are used for? My samples
Analgesics pain pills headaches, muscle aches and pains Aleve (napro
Aspirin
Celebrex (ce
Codeine
Motrin (ibup
Tylenol (ace
Antacids indigestion heartburn Prevacid (lan
pills Prilosec (om
Tums
 98

Zantac (ranit
Antiarthritic rheumatism pills rheumatoid arthritis Aspirin
Aleve (napro
Celebrex (ce
Humira (ada
Remicade (in
Antibiotics bug killers microbial infections Amoxil (amo
Erythromyci
Keflex (ceph
Pen-Vee (Pe
Septra (sulfa
Vibramycin
Anticoagulants blood thinners prevent blood clots Coumadin (w
Heparin
Plavix (clopi
Anticonvulsants epilepsy drugs prevent seizures Dilantin (phe
Phenobarbita
Neurontin
(gabapentin)
Antidepressants uppers relieve depression Elavil (amitr
Prozac (fluox
Zoloft (sertra
Antihistamines cold and flu pills stops runny nose, wheezing and itchiness Allegra (fexo
Benadryl (di
Claritin (lora
Antihyperlipidemics cholesterol pills lowers cholesterol levels Lipitor (atorv
Niaspan (Nia
Pravachol (p
Questran (ch
Zocor (simva
Antihypertensives blood pressure pills lowers high blood pressure Norvasc (am
Captopen (ca
Inderal (prop
Lotensin (be
Tenormin (at
Zestril (lisino
Cardiac drugs heart medicine treats abnormal heart rhythms, heart failure, angina Cardizem (di
pain Cordarone (a
Inderal (prop
Lanoxin (dig
Nitrostat (nit
Diuretics w lowers high blood pressure, treat congestive heart Hydrodiuril (
ater pills failure Lasix (furose
Erectile Dysfunction man’s best friend impotency Cialis (tadala
Levitra(vard
Viagra (silde
Hypnotics sleeping pills insomnia Ambien (zol
Lunesta (esz
Sonata (zalep
Hypoglycemic agents diabetic drugs lowers high blood sugar Diabeta (Gly
Glucophage
Glucotrol (gl
Insulin
Osteoporosis therapy mom’s bone pills strengthens bones Actonel (rise
Boniva (iban
 99

Fosamax (ale
Tranquilizers downers anxiety Valium (diaz
Xanax (alpra

EXTRA NOTES ON MEDICAL VOCABULARY

Word Meaning Example sentence

part of speech
abnormal not normal for the human body This amount of weight loss is abnormal for women your age.
adj
ache pain that won't go away I can't sleep because my knees ache in the night.
noun/verb
acute quick to become severe/bad We knew the baby was coming right away because the woman
adj
allergy noun a body's abnormal reaction to certain foods Your son is extremely allergic to peanuts.
allergic adj or environmental substances (eg causes a rash)
ambulance emergency vehicle that rushes people to a We called the ambulance when Josh stopped breathing.
noun hospital
amnesia a condition that causes people to lose their I can't remember the accident because I had amnesia.
noun memory
amputation permanent removal of a limb We had to amputate his leg because the infection spread so q
noun
amputate verb
anaemia noun occurs when the body doesn't have enough red I have low energy because I am anaemic.
anaemic adj blood cells
antibiotics medication that kills bacteria and cures My throat infection went away after I started the antibiotics.
noun infections
anti-depressant medication that helps relieve anxiety and The anti-depressants helped me get on with life after Lucy d
noun sadness
appointment a scheduled meeting with a medical I've made you an appointment with a specialist in three week
noun professional
arthritis a disease that causes the joints to become My grandmother can't knit anymore because the arthritis in
noun swollen and crippled
asthma (attack) a condition that causes a blockage of the airway I carry an inhaler when I run because I have asthma.
noun and makes it difficult for a person to breathe
bacteria a disease-causing organism To prevent the spread of bacteria it is important that nurses
noun
bedsore wounds that develop on a patient's body from If you don't get up and take a walk, you will develop painful b
noun lying in one place for too long
benign not harmful (not cancerous) We're hoping that the tests will show that the lump in your br
adj
biopsy removal of human tissue in order to conduct The biopsy ruled out a number of illnesses.
noun certain medical tests
 100

blood count the amount of red and white blood cells a You will be happy to know that your blood count is almost ba
noun person has
blood donor a person who gives blood to a blood bank or Blood donors have to answer questions about their medical h
noun other person
blood pressure the rate at which blood flows through the body High blood pressure puts you at risk of having a heart attack
noun (high/low)
brace a device that holds injured body parts in place You will probably always have to wear a brace on your ankle
noun
breech position of an unborn baby in which the feet are We thought it was going to be a breech birth, but the baby tur
adj down and the head is up
broken a bone that is divided in two or more pieces as a We thought it was just a sprain, but it turned out his leg was b
adj result of an injury
bruise noun injured body tissue that is visible underneath The woman was badly bruised when she came into the emerg
bruised adj the skin
Caesarean procedure that involves removing a baby from The baby was so large that we had to perform a Caesarean se
section, C- its mother through an incision in the woman's
section lower abdomen
noun
cancer disease caused by the uncontrollable growth of There are many different options when it comes to treating ca
noun cells
cardiopulmonar restoring a person's breath and circulation You saved your brother's life by performing CPR.
y resuscitation
(CPR)
noun
cast a hard bandage that is wrapped around a My leg was in a cast for graduation.
noun broken bone to keep it in place
chapel, a place where loved ones can go to pray for a If you want a place to pray, the chapel is on the third floor.
chapeline patient's recovery;
noun a priest who visits patients in the hospital
chemotherapy type of treatment used on cancer patients My mother has already had three rounds of chemotherapy.
noun
chickenpox a virus commonly contracted by children, It is best to get chickenpox as a child so that you don't get it w
noun characterized by itchy spots all over the body
coroner a person who determines the cause of death We only call the coroner if we think a death is suspicious.
noun after a person dies
critical requiring immediate and constant medical You can't see her right now; she's in critical condition.
condition attention
noun
crutches objects that people with injured legs or feet use I'd rather hop on one foot than use crutches.
noun to help them walk
cyst a sac in the body-tissue filled with fluid We're going to remove the cysts just to be on the safe side.
noun (sometimes diseased)
deaf unable to hear The accident left the patient both deaf and blind.
adj
deficiency a lack of something necessary for one's health The tests show that you have an iron deficiency.
noun
dehydrated in need of water It is easy for the elderly to become dehydrated in this heat.
adj
dementia loss of mental capacity It is hard to watch a loved one suffering with dementia.
noun
diabetes type of disease typically involving insulin People with diabetes have to constantly check their blood su
noun deficiency
diagnosis medical explanation of an illness or condition The doctor would prefer to share the diagnosis with the patie
 101

noun
discomfort experiencing pain This pain medication should relieve some of your discomfort
noun
disease a medical disorder that is harmful to a person's I understand that this disease runs in your family.
noun health
dislocated when a bone is temporarily separated from its You will have to wear a sling because of your dislocated shou
adj joint
emergency a medical problem that needs immediate It is important that children know which number to dial in cas
noun attention
ER (emergency the hospital room used for treating patients The child was rushed into the ER after he had a severe allergi
room) with immediate and life-threatening injuries
noun
external on the outside This cream is for external use only. Do not get it near your ea
adj
false negative a test that incorrectly comes back negative We had two false negative pregnancy tests, so we didn't know
noun
adj
family history medical background of a person's family The doctor was concerned about my family history of skin ca
noun members
fatal causing death The doctor made a fatal error when he wrote the wrong presc
adj
fever noun higher than normal body temperature He is very feverish, and his temperature is near danger point
feverish adj
flu (influenza) many types of respiratory or intestinal People who have the flu should not visit hospital patients.
noun infections passed on through a virus
fracture noun broken or cracked bone Your wrist is fractured and needs a cast.
fractured adj
germ a micro-organism, especially one that causes Flowers are not allowed in the ward to avoid the risk
noun disease of germs being brought in.
genetic a medical condition or physical feature that is The disease is part genetic and part environmental.
adj passed on in the family
growth a ball of tissue that grows bigger than normal, That growth on your shoulder is starting to worry me.
noun either on or under the skin
heart attack instance in which blood stops pumping through People who smoke are at greater risk of having
noun the heart a heart attack.
HIV the virus that infects the human T-cells and HIV can be passed down from the mother to her fetus.
noun leads to AIDS
hives bumps that appear on the surface of the skin I broke out in hives after I ate that potato casserole.
noun during an allergic reaction
illness noun general term for any condition that makes a Her illness went away when she started eating better.
ill adj person feel sick for a certain period of time
immune system the parts of the body that fight diseases, You can't have visitors because your immune system is low.
noun infections, and viruses
immunization an injection that protects against a specific Babies are immunized three times in their first year.
noun disease
immunize verb
incision cut in the body made during surgery I had to have stitches to close the incision.
noun
inconclusive Unclear We have to do more x-rays because the first ones were inconc
adj
infant young baby The nurse will demonstrate how to bathe an infant.
noun
 102

infection noun diseased area of the body (viral or bacterial) The wound should be covered when you swim to prevent it
infected adj from becoming infected.
inflamed appearance (red and swollen) of an injured My right ankle was so inflamed it was twice the size of my lef
adj body part
injury damage to the body Her injuries were minor; just a few cuts and bruises.
noun
intensive care section of the hospital where patients get She will remain in the ICU until she can breathe on her own.
unit (ICU) constant attention and doctors rely on
noun specialized equipment
internal under the skin, inside the organs The doctors will be monitoring her for any internal
adj bleeding.
itchy feeling discomfort on the skin's surface If you are allergic to this medication your skin will get red and
adj
IV a tube that pumps liquids and medication into a The toddler was so dehydrated that the doctor decided to get
noun patient's body
lab results tests that come back from a laboratory and help The lab results have come in and you are free to go home.
noun doctors make a diagnosis
lab (laboratory) place where samples of blood/urine etc. are I'll take these samples down to the lab on my way out.
noun taken for testing
life support a machine that keeps patients alive by helping The woman has severe brain damage and is currently on life s
noun them breathe
life-threatening when injuries and conditions are extremely The victim was shot in two places but the bullet wounds are n
adj serious
light-headed feeling of dizziness and being off-balance, If you are feeling light-headed again, lie down and call me.
adj caused by lack of oxygen in the brain
malignant expected to grow and get much worse I'm afraid at least one of the tumours is malignant.
adj (especially related to cancerous cells)
medical school place where someone trains to be a doctor After eight years of medical school I can finally practice med
(med. school)
noun
newborn an infant that is less than three months old You have to support her neck because she is still a newborn.
noun
numb no feeling in a certain body part The needle will make your lower body feel numb.
adj
OR (operating the place where major surgeries and operations You must wear a face mask and gloves while you are in the OR
room) take place
noun
operation noun a medical procedure that involves going inside a The operation lasted seven hours, but it was successful.
operate on verb person's body in an attempt to fix a problem
pain strong discomfort in certain areas of the body We gave your husband some medicine to relieve some of the p
noun
pain killer, pain type of medicine that takes away some or all of You can take two pain killers every four hours.
reliever the discomfort of an illness or injury
noun
paralyzed unable to move certain areas of the body We thought her legs were paralyzed for life, but she is learnin
adj
patient a person staying in a hospital or medical facility The patients in Room 4 are not getting along.
noun
pharmacist a person who fills a doctor's prescription and Ask the pharmacist if there is a generic brand of this medicat
noun gives people advice about medication
pharmacy, a place where people go to buy medication and You should be able to buy a bandage at the pharmacy.
drugstore other medical supplies
noun
 103

physician Doctor Ask your family physician to refer you to a specialist.

noun
poison noun a substance that is very dangerous if it enters The child was bitten by a poisonous snake.
poisonous adj the human body
prenatal of the time period leading up to giving birth The woman was well prepared for labour because she took th
adj
prescription the correct amount and type of medication You will need to visit your doctor to get another prescription
noun needed to cure an illness or relieve symptoms
prescribe verb
privacy noun being alone; personal (eg test results) You will have to pay for a private hospital room if you don't w
private adj
radiation high energy X-rays that destroy cancer cells If the radiation doesn't kill all of the abnormal cells, the cance
noun
residency part of a doctor's training that takes place in the John is a resident under Dr Brown.
resident hospital;
noun a student working under a doctor
routine check- a doctor's appointment to check a person's I'd like to see you a year from now for a routine check-up.
up general health
noun
scrubs plain uniform (usually green, white, or blue) I have some extra scrubs in my locker.
noun worn by medical professionals
scrub up carefully wash hands before and after seeing a I have to scrub up and get ready for surgery.
verb patient
second opinion input from a second doctor about an illness or I went to another doctor to get a second opinion about these
noun symptom
seizure sudden violent movements or unconsciousness People who suffer from epilepsy are prone to seizures.
noun caused by electrical signal malfunction in the
brain
shock body not getting enough blood flow The woman was in shock after being pulled from the river.
noun
side effects other symptoms that might occur as a result of a One of the side effects of antidepressants is a loss of appetite
noun certain medication or procedure
sore Painful I have a sore throat and a runny nose.
adj
spasm the uncontrollable tightening of a muscle Ever since I injured my leg I've been having muscle spasms in
noun
specialist a doctor that is an expert in a certain kind of My family doctor is sending me to a specialist.
noun medicine
sprain an injury (less serious than a break) to a joint I sprained my knee playing soccer.
noun/verb (ankle, wrist, knee etc)
stable condition a patient is stable if their medical condition is You can see your husband now; he is in a stable condition.
noun no longer changing rapidly
sting sharp, temporary pain It may sting when I insert the needle.
noun/verb
stress noun worry that causes muscles to tighten and blood You need to take some time off work and relieve some of your
stressed adj pressure to rise
swelling noun ligaments (parts that hold the joints together) I knew my ankle was sprained because it was so swollen.
swollen adj growing bigger and rounder after an injury to a
joint
symptoms pain or physical changes that occur because of You have all of the symptoms of a diabetic.
noun an illness or disease
temperature amount of heat measured in a body; higher than We brought Jesse to emergency because he was running a (hig
noun normal temperature
 104

tender painful when touched or used The incision was tender after the surgery.
adj
test results medical information that helps doctors The test results came back negative. You aren't pregnant.
noun understand a patient's condition or body
therapy treatment aimed at improving a person's I was able to go back to work a few weeks after starting the th
noun mental or physical condition
transplant moving of an organ from one human to another The heart transplant saved your life.
noun
ultrasound a test that examines the body's internal organs The ultrasound shows that we are expecting a baby boy.
noun and processes using sound waves (often used
during pregnancies)
umbilical cord the lifeline from the mother to the fetus (when I had an emergency C-section because the umbilical cord wa
noun cut at birth this forms the belly button)
unconscious alive, but appearing to be asleep and unaware of I hit my head on the steering wheel and was still unconscious
adj the surroundings
urine sample a small amount of the body's liquid waste that is The urine sample tells us how much alcohol is in your blood.
noun tested for different medical reasons
vein the thin tubes that transport blood around the I'm just looking for the best vein in which to insert the needle
noun body and back to the heart
virus a dangerous organism that causes the spread of The virus is contractable through the exchange of bodily fluid
noun minor and major diseases
visiting hours time of day when friends and family are allowed I'm afraid you'll have to come back during visiting hours.
noun to visit patients in hospital
vomit discharge of a person stomach contents through The pregnant woman can't stop vomiting.
noun/verb the mouth
ward a section of a hospital or health facility where I should warn you that we're entering the mental health ward
noun patients stay
wheelchair a chair on wheels used for transporting patients If you get in the wheelchair I'll take you down to see the gard
noun from place to place
wound noun injury to body ("flesh wound" means not deep) The wounded soldiers are being airlifted to the hospital.
wounded adj
x-ray a photograph of a person's bones and organs The technician took x-rays of my shoulder to make sure it wa
noun/verb

SEEING THE DOCTOR

Describing aches and pains

If your head hurts:
If your stomach hurts:
If your back hurts:
If your neck hurts:
If other parts of your body hurt:
"I've got a headache." or "My head aches."
"I've got stomach ache." or "My stomach aches."
"I've got backache." or "My back aches."
"I've got neckache." or ""My neck aches."
"I've got a pain in my arm / leg etc."
 105

Dialogue

It's Monday morning and Mr Smith has gone to see the doctor.
Doctor: Hello Mr Smith. We haven't seen you in a while. What seems to be the problem?
Mr Smith Well, I fell off the ladder whilst I was decorating and hurt my ankle. It swelled up and hasn't
gone down since.
Doctor: OK - let's have a look, take off your shoe and sock and roll up your trouser leg.

(Examines ankle)

Ah yes, I think we had better send you to the hospital to get this X-rayed. You may have
broken a bone.
Mr Smith: What? You're joking! No wonder it hurts so much.

The human body

Here are the English names for parts of the human body, as well as the words for different senses.

Head and face

beard
cheek
chin
head
hair
ear
eye
eyebrow
eardrum
earlobe
eyelash
eyelid
forehead
freckles
jaw
lip
mouth
nose
nostril
moustache
tongue
tooth (plural: teeth)
wrinkles
 106

Upper body
Adam's apple
arm
armpit
back
breast
chest
elbow
hand
finger
fingernail
forearm
knuckle
navel or belly button
neck
nipple
palm
shoulder
throat
thumb
waist
wrist

Lower body
ankle
anus
belly
big toe
bottom (slang: bum)
buttocks
calf
foot (plural: feet)
genitals
groin
heel
hip
knee
leg
penis
pubic hair
shin
sole
testicles
thigh
 107

toe
toenail
vagina

Parts of the eye

cornea
eye socket
eyeball
iris
retina
pupil

Internal body parts

Achilles tendon
artery
appendix
bladder
blood vessel
brain
cartilage
colon
gall bladder or gallbladder
heart
intestines
large intestine
small intestine
kidneys
ligament
liver
lungs
oesophagus
pancreas
organ
prostate gland or prostate
rectum
spleen
stomach
tendon
tonsils
vein
windpipe
womb or uterus
 108

Bones
collarbone or clavicle
thigh bone or femur
humerus
kneecap
pelvis
rib
rib cage
skeleton
skull
spine or backbone
vertebra (plural: vertebrae)

Body fluids
bile
blood
mucus
phlegm
saliva or spit
semen
sweat or perspiration
tears
urine
vomit

Other related words

bone
fat
flesh
gland
joint
limb
muscle
nerve
skin
digestive system
nervous system
to breathe
to cry
to hiccup
to have the hiccups
to sneeze
to sweat or to perspire
to urinate
 109

to vomit
to yawn

Senses
smell
touch
sight
hearing
taste
to smell
to touch
to see
to hear
to taste

Human Body Vocabulary Word List

A E cont. L S
abdomen endocrine system larynx sacrum
Adam's apple esophagus leg scalp
adenoids eye ligament scapula
adrenal gland eyebrow lip senses
anatomy eyelashes liver shin
ankle eyelid lobe shoulder
anus F lumbar vertebrae shoulder blade
appendix face lungs skeleton
arch fallopian tubes lymph node skin
arm feet M skull
artery femur mandible sole
B fibula metacarpal spinal column
back filling metatarsal spinal cord
ball of the foot finger molar spine
belly fingernail mouth spleen
belly button follicle muscle sternum
big toe foot N stomach
bladder forehead nail T
blood G navel tarsal
blood vessels gallbladder neck teeth
body glands nerves tendon
bone groin nipple testes
brain gums nose thigh
breast H nostril thorax
buttocks hair O throat
C hand organs thumb
 110

calf head ovary thyroid

capillary heart P tibia
carpal heel palm tissue
cartilage hip pancreas toe
cell humerus patella toenail
cervical vertebrae I pelvis tongue
cheek immune system phalanges tonsils
chest instep pharynx tooth
chin index finger pinky torso
circulatory system intestines pituitary trachea
clavicle iris pore U
coccyx J pupil ulna
collar bone jaw R ureter
D K radius urethra
diaphragm kidney rectum urinary system
digestive system knee red blood cells uterus
E respiratory system uvula
ear ribs V
ear lobe vein
elbow vertebra
W
waist
white blood cells
wrist

1. arteries : Any of the blood vessels that carry

blood away from the heart to all parts of the body
2. heart : The muscular organ inside the chest that pumps blood through the
body
3. blood: The red liquid that flows throughout the bodies of humans
4. veins : One of the blood vessels through which the blood flows to the heart
from all parts of the body
5. blood vessels : Tubes in the body through which blood circulates
6. capillaries : Blood vessels that join the end of an artery to the beginning of a vein
7. gallbladder : A sac attached to the liver, in which extra bile is stored until needed
8.
esophagus
The passage for food from the mouth to travel to the stomach
9.
large intestine
The lower part of the intestine,
including the appendix, colon, and
rectum
10.
mouth
 111

The section of the body containing

the tongue and teeth which opens
to allow food to pass through
11.
stomach
The large organ like a bag or pouc
h into which food passes from the
mouth and throat to begin the process of digestion
12.
liver
A large reddish-brown organ in people and animals that helps the
body absorb food
13.
pancreas
A gland near the stomach that helps digestion
14.
small intestine
The slender part extending from the st
omach to the large intestine that
completes the digestion of food
Human Body
Vocabulary Words Week 2
1.
skull
The bones of the head that surround and protect the brain
2.
ribs
Narrow bones that curve around the body
from the spine in back to the
breastbone in front. Ribs protect the organs inside
3.
humerus
The long bone of the upper arm that extends from shoulder to elbow
4.
vertebrae
Bones that form the backbone
5.
pelvis
A basin-shaped structure in the skeleton
6.
ulna
The bone on the little finger side of the forearm
7.
radius
The bone on the thumb si
de of the forearm
8.
carpals
The bones of the wrist
9.
metacarpals
The bones in the hand
10.
phalanges
Any bone in the fingers or toes
11.
 112

femur
The long bone of the leg extendi
ng from the hip to the knee and
supporting the thigh
12.
patella
the kneecap
13.
tibia
The inner and usually larger of the
two bones of the vertebrate hind leg
between the knee and the ankl
e – also called the shinbone
14.
fibula
The outer and usually smaller of th
e two bones of the hind limb below
the knee
15.
tarsals
The small bones in the foot between th
e metatarsus and the leg – ankle
16.
metatarsals
The bones in the foot
Human Body
Vocabulary Words Week 3
1.
nose
A body part on the face just below the eyes, through which air
passes and through
which one smells
2.
pharynx
The space behind the cavity of th
e mouth into which the nostrils
and esophagus open
3.
larynx
The upper portion of the windpipe th
at contain the vocal cords –
voice box
4.
trachea
The main part of the system of
tubes by which air passes to and
from the lungs to make breathing possible
5.
bronchial tubes
A branch of the windpipe that br
ings air to and from the lungs –
the windpipe
6.
lungs
One of the pair od organs for br
eathing found in the chest. The
 113

lings take in oxygen from the ai

r and remove carbon dioxide from
the blood
7.
alveoli
Air cells in the lungs
8.
respiration
The process of taking in oxygen and giving off carbon dioxide
which is breathing
9.
exhale
To breathe out
10.
inhale
To breathe air into the lungs
Human Body
Vocabulary Words Week 4
1.
involuntary muscle
A muscle that works or moves on its own
2.
voluntary muscle
A muscle that can be controlled
3.
joint
A place in the body where bones come
together and movement can
occur
4.
ligament
A tough, flexible connecting tissue th
at attaches one bone to another
bone at a joint
5.
nerve
Cells along which messages are ca
rried to and from the brain
6.
organ
Groups of tissues working together
7.
reflex
An involuntary response not controlled by the brain
8.
medulla
The smallest part of the brain that controls many involuntary
movements
9.
cell
The smallest unit of an organism th
at carries out all activities of life
10.
cerebellum
The part of the brain that sm
oothes and coordinates movement
 114

11.
cerebrum
The part of the brain that controls
the ability to think, learn, and talk
12.
sensory nerve
A nerve that receives messages fro
m inside or outside the body and
sends them to the brain by way of the spinal cord
13.
skeleton
A hard structure that supports and protects and animal or human’s
body
14.
spinal cord
A thick, cordlike bundle of nerves
along which messages ftravel to
and from the brain
15.
tendon
A tough, white band of connecting
tissue that attaches skeletal
muscle to bone
16.
tissue
Different cells working together to do the same job
17.
oxygen
A gas having no color, smell, or
taste that humans need to live
18.
carbon dioxide
A gas made of carbon
and oxygen having no colo
r or smell. When
we breathe out, we put carbon dioxide into the air
19.
ventricle
Either of the two lower chambers
of the heart that receive blood
from the auricles and for
ces it into the artieries
20.
atrium
The chambers of the heart that
receives the blood from the veins
 115

1. artery

a blood vessel that carries blood from the heart to the body

2. atrium

a chamber connected to other chambers or passageways

3. bile

a digestive juice secreted by the liver

4. cardiac muscle

the muscle tissue of the heart

5. cartilage

tough elastic tissue, mostly converted to bone in adults

6. diaphragm

a muscular partition in the chest used in respiration

7. epiglottis

a flap of cartilage that covers the windpipe while swallowing

8. esophagus

the passage between the pharynx and the stomach

9. hemoglobin

a hemoprotein that gives red blood cells their color

10. involuntary muscle

a muscle that contracts without conscious control and found in walls of internal organs such as stomach and
intestine and bladder and blood vessels (excluding the heart)

11. larynx

the structure containing the vocal cords

12. ligament

a band of fibrous tissue connecting bones or cartilages

13. nephron

any of the small tubules that are the excretory units of the vertebrate kidney

14. periosteum

a dense fibrous membrane covering the surface of bones (except at their extremities) and serving as an
attachment for tendons and muscles; contains nerves and blood vessels that nourish the enclosed bone
 116

15. plasma

the watery fluid in which blood cells are suspended

16. red blood cell

a mature blood cell that contains hemoglobin to carry oxygen to the bodily tissues; a biconcave disc that
has no nucleus

17. saliva

a clear liquid secreted into the mouth by the salivary glands and mucous glands of the mouth; moistens the
mouth and starts the digestion of starches

18. smooth muscle

a muscle that contracts without conscious control and found in walls of internal organs such as stomach and
intestine and bladder and blood vessels (excluding the heart)

19. tendon

a band of tissue connecting a muscle to its bony attachment

20. urea

the chief solid component of mammalian urine

21. vein

a blood vessel that carries blood toward the heart

22. ventricle

a chamber of the heart that receives blood from an atrium

23. voluntary muscle

striated muscle that can be controlled voluntarily

24. white blood cell

blood cells that engulf and digest bacteria and fungi

Body Parts
arm
eye
eyebrow
belly
leg
breast
 117

thumb
elbow
fist
finger
foot (plural: feet)
ankle
buttocks
hair
neck
hand
wrist
hip
chin
knee
head
lip
mouth
nose
nostril
upper arm
thigh
ear
bottom, bum
back
underarm, forearm
lower leg
shoulder
forehead
waist
calf (plural: calves)
cheek
eyelash, lash
tooth (plural: teeth)
toe
tongue

Dysmenorrhea, also known as painful periods, or menstrual cramps, is pain during menstruation.[1][2] It usually
begins around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in
the pelvis or lower abdomen. Other symptoms may include back pain, diarrhea, or nausea.[1]

In young women painful periods often occur without an underlying problem. In older women it is more often due to
an underlying issues such as uterine fibroids, adenomyosis, or endometriosis.[3] It is more common among those with
heavy periods, irregular periods, whose periods started before twelve years of age, or who have a low body weight.[1]
A pelvic exam in those who are sexually active and ultrasound may be useful to help in diagnosis.[1] Conditions that
should be ruled out include ectopic pregnancy, pelvic inflammatory disease, interstitial cystitis, and chronic pelvic
pain.[1]

Dysmenorrhea occurs less often in those who exercise regularly and those who have children early in life.[1]
Treatment may include the use of a heating pad.[3] Medications that may help include NSAIDs such as ibuprofen,
hormonal birth control, and the IUD with progestogen.[1][3] Taking vitamin B or magnesium may help.[2] Evidence
for yoga, acupuncture, and massage is insufficient.[1] Surgery may be useful if certain underlying problems are
present.[2]
 118

Dysmenorrhea is estimated to occur in 20% to 90% of women of reproductive age.

It is the most common menstrual disorder. Typically it starts within a year of the first menstrual period.

When there is no underlying

cause often the pain improves with age or following having a child.

What Are Menstrual Cramps?

(from http://www.webmd.com/women/menstrual-cramps#1)

Having menstrual cramps is one of the most common, annoying parts of your period. They can strike right before or
during that time of the month. Many women get them routinely.

You’ll feel these cramps in your lower belly or back. They can range from mild to severe. They usually happen for
the first time a year or two after a girl first gets her period. With age, they usually become less painful and may stop
entirely after you have your first baby.

Your doctor may call your cramps “dysmenorrhea.”

Symptoms
Chances are, you know all too well how it feels. You may have:

• Aching pain in your belly (sometimes severe)

• Feeling of pressure in your belly

• Pain in the hips, lower back, and inner thighs

When cramps are severe, symptoms may include:

• Upset stomach, sometimes with vomiting

• Loose stools

Pregnancy Symptoms

Are you wondering if you might be pregnant? The only way to know for sure is by taking a pregnancy test.

But there are early symptoms of pregnancy that may point to the possibility. Here's what to look for.

Do All Women Get Early Symptoms of Pregnancy?

Every woman is different. So are her experiences of pregnancy. Not every woman has the same symptoms or even
the same symptoms from one pregnancy to the next.
 119

Also, because the early symptoms of pregnancy often mimic the symptoms you might experience right before and
during menstruation, you may not realize you're pregnant.

What follows is a description of some of the most common early symptoms of pregnancy. You should know that
these symptoms may be caused by other things besides being pregnant. So the fact that you notice some of these
symptoms does not necessarily mean you are pregnant. The only way to tell for sure is with a pregnancy test.