BIOCHEM-TRANS With Additional Protein Topic

PHARM 13: PHARMACEUTICALS IN BIOCHEMISTRY
JESSA MAE V. SELEDIO  USM – COLLEGE OF MEDICINE AND ALLIED HEALTH SCIENCES
MS. JEZZA MAY B MANUEL  ADAPTED FROM: BOOK
CARBOHYDRATES • Nucleolus – site of ribosome assembly

• Nuclear membrane
BIOCHEMISTRY – AN OVERVIEW
OCCURRENCE AND FUNCTIONS OF
• The study of the chemical substances found in living
organisms and the chemical interactions of these CARBOHYDRATES
substances with each other. CARBOHYDRATES
• A field in which new discoveries are made almost daily • The most abundant class of bioorganic molecules on planet
about how cells manufacture the molecules needed for life Earth.
and how the chemical reactions by which life is maintained • Mean “Hydrates of Carbon”
occur. • Although their abundance in the human body is relatively
BIOCHEMICAL SUBSTANCE low, carbohydrates constitute about 75% by mass of dry
• Is a chemical substance found within a living organism. plant materials.
• Divided into two groups: • Green (chlorophyll-containing) plants produce
carbohydrates via photosynthesis.
o In this process, carbon dioxide from the air and water
from the soil are the reactants, and sunlight absorbed
by chlorophyll is the energy source.
• Plants have two main uses for the carbohydrates they

produce.
o Cellulose – they serve as structural element
o Starch – they provide energy reserves for the plants.
• Dietary intake of plant materials is the major carbohydrate
source for humans and animals.
• The average human diet should ideally be about two-thirds
carbohydrate by mass.
• Although the human body is usually thought of as CARBOHYDRATES HAVE THE FOLLOWING FUNCTIONS
containing mainly organic (biochemical) substances, such IN HUMANS:
substances make up only about one-fourth of total body (1) Carbohydrate oxidation provides energy.
mass. (2) Carbohydrate storage, in the form of glycogen, provides a
• The bioinorganic substance water constitutes more than short-term energy reserve.
two-thirds of the mass of the human body, and another 4%– (3) Carbohydrates supply carbon atoms for the synthesis of
5% of body mass comes from inorganic salts. other biochemical substances (proteins, lipids, and nucleic
OVERVIEW OF MOLECULAR BIOLOGY: PARTS OF THE CELL acids).
(4) Carbohydrates form part of the structural framework of
CELL MEMBRANE DNA and RNA molecules.
• Phospholipids (5) Carbohydrates linked to lipids are structural components
• Glycoproteins and Glycolipids of cell membranes.
• Cholesterol (6) Carbohydrates linked to proteins function in a variety of
• Arachidonic Acid cell–cell and cell–molecule recognition processes.
ORGANELLES BIOMOLECULES BUILDING BLOCKS
• Mitochondrion
Carbohydrates Simple sugars
o Powerhouse of the cell that also produces ATP
(energy) Lipids Fatty acids
• Ribosomes
Proteins Amino acids
o Protein synthesis
▪ Prokaryote: 30s, 50s = 70s Nucleic acids Nucleotides
▪ Eukaryotes: 40s, 60s = 80s
• Lysosomes CLASSIFICATION OF CARBOHYDRATES
o Suicide bag of the cell • Most simple carbohydrates have empirical formulas that fit
o Has enzymes and free radicals (when release will the general formula CnH2nOn.
cause Apoptosis; programmed cell death) • Can also be written as Cn(H2O)n is the basis for the term
• Endoplasmic reticulum carbohydrate—that is, “hydrate of carbon.”
o Smooth ER – lipid synthesis • Is a polyhydroxy aldehyde, a polyhydroxy ketone, or a
o Rough ER – protein synthesis compound that yields polyhydroxy aldehydes or
• Golgi apparatus polyhydroxy ketones upon hydrolysis.
o Packaging and storage of substance of the cell • The carbohydrate glucose is a polyhydroxy aldehyde,
NUCLEUS and the carbohydrate fructose is a polyhydroxy ketone
• Control center of the cell
• Chromosomes – tightly coiled DNA strands (46 Chr)
2  CARBOHYDRATES AND CARBOHYDRATE METABOLISM
CLASSIFICATION OF CARBOHYDRATES
MONOSACCHARIDE
• Is a carbohydrate that contains a single polyhydroxy
aldehyde or polyhydroxy ketone unit.
• Monosaccharides cannot be broken down into simpler
units by hydrolysis reactions.
• Both glucose and fructose
• Naturally occurring monosaccharides have from three to
seven carbon atoms; five- and six-carbon species are HYDROLYSIS
especially common.
• Pure monosaccharides are water-soluble, white,
crystalline solids.
DISACCHARIDE
• Is a carbohydrate that contains two monosaccharide units
covalently bonded to each other.
• Like monosaccharides, disaccharides are crystalline,
water-soluble substances.
• Sucrose (table sugar) and lactose (milk sugar)
• Hydrolysis of a disaccharide produces two
monosaccharide units.
OLIGOSACCHARIDE
• Is a carbohydrate that contains three to ten
monosaccharide units covalently bonded to each other.
• “Free” oligosaccharides are seldom encountered in CHIRALITY: HANDEDNESS IN MOLECULES
biochemical systems. MIRROR IMAGES
• They are usually found associated with proteins and lipids
• Is the reflection of an object in a mirror.
in complex molecules that have both structural and
• Objects can be divided into two classes on the basis of
regulatory functions.
their mirror images:
• Complete hydrolysis of an oligosaccharide produces
several monosaccharide molecules; a trisaccharide SUPERIMPOSABLE MIRROR IMAGES
produces three monosaccharide units, a hexasaccharide • Are images that coincide at all points when the images are
produces six monosaccharide units, and so on. laid upon each other.
POLYSACCHARIDE • A dinner plate with no design features has superimposable
mirror images
• Is a polymeric carbohydrate that contains many
monosaccharide units covalently bonded to each other. NONSUPERIMPOSABLE MIRROR IMAGES
• The number of monosaccharide units present in a • Are images where not all points coincide when the images
polysaccharide varies from a few hundred units to more are laid upon each other.
than a million units. • Human hands are nonsuperimposable mirror images
• Polysaccharides, like disaccharides and oligosaccharides,
CHIRALITY
undergo hydrolysis under appropriate conditions to
produce monosaccharides • For organic and bioorganic compounds, the structural
requirement for handedness is the presence of a carbon
NATURAL OCCURING POLYSACCHARIDES
atom that has four different groups bonded to it in a
CELLULOSE tetrahedral orientation.
• Paper in books, cotton in clothing fabrics and the wood CHIRAL CENTER
used in home construction.
• Is an atom in a molecule that has four different groups
STARCH bonded to it in a tetrahedral orientation.
• A component of many types of foods, including bread, CHIRAL
pasta, potatoes, rice, corn, beans, and peas.
• A molecule that contains a chiral center
CHIRAL MOLECULE THERE ARE TWO MAJOR STRUCTURAL FEATURES THAT
GENERATE STEREOISOMERISM
• Is a molecule whose mirror images are not
superimposable. (1) the presence of a chiral center in a molecule and
(2) the presence of “structural rigidity” in a molecule.
• Chiral molecules have handedness.
ACHIRAL MOLECULE STRUCTURAL RIGIDITY
• Is caused by restricted rotation about chemical bonds.
• Is a molecule whose mirror images are superimposable.
• It is the basis for cis–trans isomerism, a phenomenon
• Achiral molecules do not possess handedness.
found in some substituted cycloalkanes and some alkenes.
Chiral centers within molecules are often denoted by a small • Thus, handedness is this text’s second encounter with
asterisk. Note the chiral centers in the following molecules. stereoisomerism.
STEREOISOMERS CAN BE SUBDIVIDED INTO TWO
TYPES:
ENANTIOMERS
• Are stereoisomers whose molecules are
nonsuperimposable mirror images of each other.
• Left- and right-handed forms of a molecule with a single
chiral center are enantiomers.
DIASTEREOMERS
• Are stereoisomers whose molecules are not mirror images
of each other.
• Cis–trans isomers (of both the alkene and the cycloalkane
types) are diastereomers
GUIDELINES FOR IDENTIFYING CHIRAL CENTERS
(1) A carbon atom involved in a multiple bond (double or
triple bond) cannot be a chiral center since it has fewer
than four groups bonded to it. To have four groups present,
all bonds about the chiral center must be single bonds.
(2) A carbon atom that has two like groups bonded to it cannot
be a chiral center since it does not meet the requirement
of four different groups. The commonly encountered
entities -CH3 and -CH2+ in a structural formula never
involve chiral centers because of the presence of two or
more like hydrogen atoms.
(3) Carbon atoms in a ring system, if not involved in multiple
bonding, can be chiral centers. Such carbon atoms have
four bonds—two to neighboring atoms in the ring and two
to substituents on the ring. Chirality occurs when both
a. the two substituents are different and DESIGNATING HANDEDNESS USING FISCHER
b. the two “halves” of the ring emanating from the PROJECTION FORMULAS
chiral center are different. This “difference in ring
FISCHER PROJECTION FORMULAS
halves” .
• A two-dimensional structural notation for showing the
spatial arrangement of groups about chiral centers in
molecules.
• A chiral center is represented as the intersection of vertical
and horizontal lines.
STEREOISOMERISM: ENANTIOMERS AND

DIASTEREOMERS
The arrangement of the four groups attached to the atom at the
ISOMERS chiral center is specified using conventions based on the
• The left- and right-handed forms of a chiral molecule following interpretation for a printed three-dimensional model
• Same molecular formula; different compounds of the tetrahedral bond orientations about the chiral center.
CONSTITUTIONAL ISOMERS 1. The central atom (the chiral center) is considered to be in
• Same formula; different connectivity the plane of the paper.
2. Two of the bonds are considered to be directed into the
STEREOISOMERS printed page (w and z in the illustration that follows).
• Are isomers that have the same molecular and structural 3. Two of the bonds are considered to be directed out of the
formulas but differ in the orientation of atoms in space. printed page (x and y in the illustration that follows).
The conventions that connect these model specifications with a

Fischer projection formula are
EPIMERS
1. Vertical lines from the chiral center in a Fischer projection
• Are diastereomers whose molecules differ only in the
formula represent bonds to groups directed into the
configuration at one chiral center.
printed page (w and z).
2. Horizontal lines from the chiral center in a Fischer In general, a compound that has n chiral centers may exist in a
projection formula represent bonds to groups directed out maximum of 2n stereoisomeric forms. For example, when three
of the printed page (x and y). chiral centers are present, at most eight stereoisomers (2 3=8) are
possible (four pairs of enantiomers)
The Fischer projection formula thus becomes
PROPERTIES OF ENANTIOMERS
CONSTITUTIONAL ISOMERS
• Differ in most chemical and physical properties.
• For example, constitutional isomers have different boiling
points and melting points.
DIASTEREOMERS
The simplest monosaccharide that has a chiral center is the • Differ in most chemical and physical properties.
three-carbon polyhydroxy aldehyde glyceraldehyde (2,3- • They also have different boiling points and melting points.
dihydroxypropanal).
ENANTIOMERS
• In contrast, nearly all the properties of a pair of
enantiomers are the same; for example, they have identical
boiling points and melting points.
• Enantiomers exhibit different properties in only two areas:
There are two stereoisomers for this compound—a pair of (1) their interaction with plane-polarized light and
enantiomers. The Fischer projection formulas for these two (2) their interaction with other chiral substances.
“mirror image” molecules are
INTERACTION OF ENANTIOMERS WITH PLANE-
POLARIZED LIGHT
• All light moves through space with a wave motion.
ORDINARY LIGHT WAVES
• That is, unpolarized light waves
• Vibrate in all planes at right angles to their direction of
The D and L designations for the handedness of the two members travel.
of an enantiomeric pair come from the Latin words dextro, which • can be converted to plane-polarized light by passing it
means “right,” and levo, which means “left.” through a polarizer
OPTICAL ACTIVITY o An instrument with lenses or filters containing
LEVOROTARY (-) special types of crystals.
• Substance rotates polarized light to the left. PLANE-POLARIZED LIGHT WAVES
• [E.g., l-glucose; (-)- glucose]. • By contrast, vibrate in only one plane at right angles to
• e enantiomer with the chiral center !OH group on the left in their direction of travel.
the Fischer projection formula is by definition the left-
When plane-polarized light is passed through a solution
handed isomer (L-glyceraldehyde).
containing a single enantiomer, the plane of the polarized light
DEXTROROTARY (+) is rotated counterclockwise (to the left) or clockwise (to the
• Substance rotates polarized light to the right. right), depending on the enantiomer.
• The enantiomer with the chiral center -OH group on the The extent of rotation depends on the concentration of the
right in the Fischer projection formula is by definition the enantiomer as well as on its identity. Furthermore, the two
right-handed isomer (D-glyceraldehyde) enantiomers of a pair rotate the plane-polarized light the same
• [E.g., d-glucose; (+)-glucose] (Dextrose is a (+)-glucose). number of degrees, but in opposite directions. If a 0.50 M
solution of one enantiomer rotates the light 300 to the right, then
a 0.50 M solution of the other enantiomer rotates the light 30 0 to
the left.
POLARIMETERS
• Instruments used to measure the degree of rotation of
plane-polarized light by enantiomeric compounds
CONSTITUTIONAL ISOMERS AND STEREOISOMERISM
CONSTITUTIONAL ISOMERS
• Isomers in which the atoms have different connectivity
SKELETAL ISOMERS
• Isomers with different carbon atom arrangements and
different hydrogen atom arrangements.
MOST OTHER DIASTEREOMERS (TWO OR MORE CHIRAL

CENTER)
• Stereoisomerism that results from
o A mirror image relationship at one (or more) chiral
centers, and
o The same configuration at one (or more) chiral
POSITIONAL ISOMERS centers
• Isomers that differ in the location of the functional group
FUNCTIONAL GROUP ISOMERS DEXTROROTATORY AND LEVOROTATORY COMPOUNDS

• Isomers that contain different functional groups
• Enantiomers are said to be optically active because of the
way they interact with plane-polarized light.
OPTICALLY ACTIVE COMPOUND
• Is a compound that rotates the plane of polarized light.
• Clockwise direction (right)
DEXTROROTATORY COMPOUND
STEREOISOMERS • Is a chiral compound that rotates the plane of polarized
light in a clockwise direction.
• Isomers with atoms of the same connectivity that differ only
in the orientation of the atoms in space. LEVOROTATORY COMPOUND
ENANTIOMERS • Is a chiral compound that rotates the plane of polarized
light in a counterclockwise direction.
• Stereoisomers that are nonsuperimposable mirror images
of each other. INTERACTIONS BETWEEN CHIRAL COMPOUNDS
• Handedness (D and L forms) is determined by the 1. Enantiomers have identical boiling points, melting points,
configuration at the high-numbered chiral center and densities because such properties depend on the
strength of intermolecular forces, and intermolecular force
strength does not depend on chirality. Intermolecular
force strength is the same for both forms of a chiral
molecule because both forms have identical sets of
functional groups.
2. A pair of enantiomers have the same solubility in an achiral
solvent, such as ethanol, but differing solubilities in a chiral
solvent, such as D-2-butanol.
DIASTEREOMERS 3. The rate and extent of reaction of enantiomers with another
• Stereoisomers that are not mirror images of each other reactant are the same if the reactant is achiral but differ if
TWO TYPES: the reactant is chiral.
4. Receptor sites for molecules within the body have chirality
CIS–TRANS ISOMERS
associated with them. Thus, enantiomers always generate
• Stereoisomerism that results from restricted rotation about
different responses within the human body as they interact
chemical bonds
at such sites. Sometimes the responses are only slightly
o Is sometimes possible when a ring is present
different, and at other times they are very different.
o Is sometimes possible when a double bond is
present The response of the body to the D isomer of the hormone is 20
times greater than its response to the L isomer of the hormone.
Epinephrine binds to its cellular receptor site by means of a
three-point
aldoses) the number of stereoisomers possible for ketotetroses,
ketopentoses, and ketohexoses. An aldohexose has four chiral
carbon atoms, but a ketohexose has only three.
BIOCHEMICALLY IMPORTANT
MONOSACCHARIDES
• Of the many monosaccharides, six that are particularly
important in the functioning of the human body are the
trioses D-glyceraldehyde and dihydroxyacetone and the D
forms of glucose, galactose, fructose, and ribose.
• Glucose and galactose are aldohexoses
• Fructose is a ketohexose
CLASSIFACTION OF MONOSACCHARIDE • Ribose is an aldopentose.
• A three-carbon monosaccharide is called a triose, and • All six of these monosaccharides are water-soluble, white,
those that contain four, five, and six carbon atoms are crystalline solids.
called tetroses, pentoses, and hexoses, respectively.
• Often called sugars. Hexoses are six-carbon sugars,
pentoses five-carbon sugars, and so on. The word sugar is
associated with “sweetness,” and most (but not all)
monosaccharides have a sweet taste.
• Based on number of Carbon Sugar
SUGAR
• A general designation for either a monosaccharide or a
disaccharide.
ALDOSE
• Is a monosaccharide that contains an aldehyde functional
group.
• Aldoses are polyhydroxy aldehydes.
• A six-carbon monosaccharide with an aldehyde functional
group is an aldohexose. D-GLYCERALDEHYDE AND DIHYDROXYACETONE
KETOSE • The simplest of the monosaccharides, these two trioses are
• Is a monosaccharide that contains a ketone functional important intermediates in the process of glycolysis, a
group. series of reactions whereby glucose is converted into two
• Ketoses are polyhydroxy ketones. molecules of pyruvate.
• A five-carbon monosaccharide with a ketone functional • D-Glyceraldehyde is a chiral molecule, but
group is a ketopentose. dihydroxyacetone is not.
D-GLUCOSE
• Of all monosaccharides, D-glucose is the most abundant in
nature and the most important from a human nutritional
standpoint. Its Fischer projection formula is
A major difference between glyceraldehyde and

dihydroxyacetone is that the latter does not possess a chiral
carbon atom. Thus, D and L forms are not possible for
dihydroxyacetone. This reduces by half (compared with
GRAPE SUGAR • The sweetest-tasting of all sugars, D-fructose is found in
• Ripe fruits, particularly ripe grapes (20%–30% glucose by many fruits and is present in honey in equal amounts with
mass), are a good source of glucose. glucose.
• It is sometimes used as a dietary sugar, not because it has
TWO OTHER NAMES FOR D-GLUCOSE
fewer calories per gram than other sugars but because less
DEXTROSE is needed for the same amount of sweetness.
• The name dextrose draws attention to the fact that the • The Chemical Connections 18-B, fructose use as a
optically active D-glucose, in aqueous solution, rotates sweetener in the form of high fructose corn syrup (HFCS).
plane-polarized light to the right. • From the third to the sixth carbon, the structure of D-
BLOOD SUGAR fructose is identical to that of D-glucose.
• Differences at carbons 1 and 2 are related to the presence
• The term draws attention to the fact that blood contains
of a ketone group in fructose and of an aldehyde group in
dissolved glucose.
glucose.
GLUCOSE
• The normal concentration of glucose in human blood is in
the range of 70–100 mg/dL (1 dL 5 100 mL).
• The actual glucose concentration in blood is dependent on
the time that has elapsed since the last meal was eaten.
• A concentration of about 130 mg/dL occurs in the first hour
after eating, and then the concentration decreases over the
next 2–3 hours back to the normal range.
• Cells use glucose as a primary source of energy
TWO HORMONES RIBOSE
INSULIN AND GLUCAGON • D-glucose, D-galactose, and D-fructose are all hexoses.
• D-Ribose is a pentose.
• Have important roles in keeping glucose blood
• If carbon 3 and its accompanying -H and -OH groups were
concentrations within the normal range, which is required
eliminated from the structure of D-glucose, the remaining
for normal body function.
structure would be that of D-ribose.
• Abnormal functioning of the hormonal control process for
blood glucose levels leads to the condition known as
diabetes.
D-GALACTOSE
• A comparison of the Fischer projection formulas for D-
galactose and D-glucose shows that these two compounds
differ only in the configuration of the -OH group and -H
group on carbon 4.
D-RIBOSE
• D-Galactose and D-glucose are epimers
• Is a component of a variety of complex molecules,
including ribonucleic acids (RNAs) and energy-rich
compounds such as ATP.
2-DEOXY-D-RIBOSE
• Is also important in nucleic acid chemistry.
• This monosaccharide is a component of DNA molecules.
• The prefix deoxy- means “minus an oxygen”;
• the structures of ribose and 2-deoxyribose differ in that the
• Seldom encountered as a free monosaccharide.
latter compound lacks an oxygen atom at carbon 2.
• In the human body, galactose is synthesized from glucose
in the mammary glands for use in lactose. CYCLIC FORMS OF MONOSACCHARIDES
o A disaccharide consisting of a glucose unit and a • Experimental evidence indicates that for monosaccharides
galactose unit containing five or more carbon atoms, such open-chain
BRAIN SUGAR structures are actually in equilibrium with two cyclic
• A component of glycoproteins found in brain and nerve structures, and the cyclic structures are the dominant forms
tissue. at equilibrium.
• D-Galactose is also present in the chemical markers that • The cyclic forms of monosaccharides result from the ability
distinguish various types of blood—A, B, AB, and O of their carbonyl group to react intramolecularly with a
hydroxyl group.
D-FRUCTOSE • Structurally, the resulting cyclic compounds are cyclic
• D-Fructose is biochemically the most important hemiacetals.
ketohexose.
• It is also known as levulose and fruit sugar.
• Aqueous solutions of naturally occurring D-fructose rotate
plane-polarized light to the left; hence the name levulose.
CYCLIC FORMS OF D-GLUCOSE AQUEOUS SOLUTION OF D-GLUCOSE
• A dynamic equilibrium exists among the α, β, and open-
chain forms, and there is continual interconversion among
them.
• For example, a freshly mixed solution of pure α -D-glucose
slowly converts to a mixture of both α - and β -D-glucose by
an opening and a closing of the cyclic structure.
• When equilibrium is established, 63% of the molecules are
β -D-glucose, 37% are α -D-glucose, and less than 0.01%
are in the open-chain form.
SPECIAL TERMINOLOGY FOR CYCLIC MONOSACCHARIDE

STRUCTURES
• Special terminology exists for the hemiacetal carbon atom
present in a cyclic monosaccharide structure.
ANOMERIC CARBON ATOM
• Is the hemiacetal carbon atom present in a cyclic
monosaccharide structure.
• It is the carbon atom that is bonded to an !OH group and to
the oxygen atom in the heterocyclic ring.
Cyclic monosaccharide formation always produces two
stereoisomers—an alpha form and a beta form. These two
STRUCTURE 2 isomers are called anomers.
• Is a rearrangement of the projection formula for D-glucose ANOMERS

in which the carbon atoms have locations similar to those • Are cyclic monosaccharides that differ only in the positions
found for carbon atoms in a six-membered ring. of the substituents on the anomeric (hemiacetal) carbon
• All hydroxyl groups drawn to the right in the original atom.
Fischer projection formula appear below the ring. α-STEREOISOMER
• Those to the left in the Fischer projection formula appear
• Has the -OH group on the opposite side of the ring from the
above the ring.
-CH2OH group
STRUCTURE 3
β -STEREOISOMER
• Is obtained by rotating the groups attached to carbon 5 in
• Has the -OH group on the same side of the ring as the -
a counterclockwise direction so that they are in the
CH2OH group.
positions where it is easiest to visualize intramolecular
hemiacetal formation.
• The intramolecular reaction occurs between the hydroxyl
group on carbon 5 and the carbonyl group (carbon 1).
• The -OH group adds across the carbon–oxygen double
bond, producing a heterocyclic ring that contains five
carbon atoms and one oxygen atom. CYCLIC FORMS OF OTHER MONOSACCHARIDES
STRUCTURE 4-6 • Intramolecular cyclic hemiacetal formation and the
• Addition across the carbon–oxygen double bond with its equilibrium between forms associated with it are not
accompanying ring formation produces a chiral center at restricted to glucose.
carbon 1, so two stereoisomers are possible. • All aldoses with five or more carbon atoms establish
• These two forms differ in the orientation of the -OH group similar equilibria, but with different percentages of the
on the hemiacetal carbon atom (carbon 1). alpha, beta, and open-chain forms.
• In α-D-glucose, the -OH group is on the opposite side of the • Fructose and other ketoses with a sufficient number of
ring from the CH2OH group attached to carbon 5. In β-D- carbon atoms also cyclize.
glucose, the CH2OH group on carbon 5 and the -OH group • Galactose, like glucose, forms a six-membered ring, but
on carbon 1 are on the same side of the ring. both D-fructose and D-ribose form a five-membered ring.
• D-Fructose cyclization involves carbon 2 (the keto group)
and carbon 5, which results in two CH2OH groups being
outside the ring (carbons 1 and 6).
• D-Ribose cyclization involves carbon 1 (the aldehyde
group) and carbon 4.
• A cyclic monosaccharide containing a six-atom ring is
called a pyranose, and one containing a five-atom ring is
called furanose because their ring structures resemble
the ring structures in the cyclic ethers pyran and furan, Comparison of this Fischer projection formula, reveals that the
respectively. monosaccharide is D-mannose. A similar matchup diagram for L-
mannose shows that all up and down positions are inverted
relative to the D-mannose diagram
HAWORTH PROJECTIONS
• Is a two-dimensional structural notation that specifies the
three-dimensional structure of a cyclic form of a
monosaccharide.
• British chemist Walter Norman Haworth
• In a Haworth projection, the hemiacetal ring system is REACTIONS OF MONOSACCHARIDE
viewed “edge on” with the oxygen ring atom at the upper • Five important reactions of monosaccharides are
right (six-membered ring) or at the top (five-membered o Oxidation to acidic sugars,
ring). o Reduction to sugar alcohols,
o Glycoside formation,
o Phosphate ester formation, and
o Amino sugar formation.
• In considering these reactions, glucose will be used as the
monosaccharide reactant.
• Remember, however, that other aldoses, as well as
ketoses, undergo similar reactions.
OXIDATION TO PRODUCE ACIDIC SUGARS
• The redox chemistry of monosaccharides is closely linked
to that of the alcohol and aldehyde functional groups.
• This latter redox chemistry is summarized in the following
diagram.
• Monosaccharide oxidation can yield three different types

In situations where a or b configuration does not matter, the -OH of acidic sugars. The oxidizing agent used determines the
group on carbon 1 is placed in a horizontal position, and a wavy product.
line is used as the bond that connects it to the ring.
WEAK OXIDIZING AGENTS
• Such as Tollens and Benedict’s solutions, oxidize the
aldehyde end of an aldose to give an aldonic acid.
• Oxidation of the aldehyde end of glucose produces
gluconic acid.
• Oxidation of the aldehyde end of galactose produces
galactonic acid.
• The structures involved in the glucose reaction are:
Any -OH group at a chiral center that is to the right in a Fischer
projection formula points down in the Haworth projection
formula. Any group to the left in a Fischer projection formula
points up in the Haworth projection formula. The following is a
matchup between Haworth projection formulas and a Fischer
projection formula.
D-SORBITOL
• The known common name of D-Glucitol
• Hexahydroxy alcohols such as D-sorbitol have properties
similar to those of the trihydroxy alcohol glycerol.
• These alcohols are used as moisturizing agents in foods
and cosmetics because of their affinity for water.
• D-Sorbitol is also used as a sweetening agent in chewing
gum; bacteria that cause tooth decay cannot use
• Because aldoses act as reducing agents in such reactions, polyalcohols as food sources, as they can glucose and
they are called reducing sugars. many other monosaccharides.
• With Tollens solution, glucose reduces Ag+ ion to Ag, and GLYCOSIDE FORMATION
with Benedict’s solution, glucose reduces Cu2+ ion to Cu+ • Hemiacetals were shown to react with alcohols in acid
ion solution to produce acetals.
REDUCING SUGAR • Because the cyclic forms of monosaccharides are
• Is a carbohydrate that gives a positive test with Tollens and hemiacetals, they react with alcohols to form acetals, as is
Benedict’s solutions. illustrated here for the reaction of β-D-glucose with methyl
• All monosaccharides, both aldoses and ketoses alcohol.
STRONG OXIDIZING AGENTS

• Can oxidize both ends of a monosaccharide at the same
time (the carbonyl group and the terminal primary alcohol
group) to produce a dicarboxylic acid.
• Such polyhydroxy dicarboxylic acids are known as
aldaric acids.
• For glucose, this oxidation produces glucaric acid.
GLYCOSIDE
• The general name for monosaccharide acetals
• Is an acetal formed from a cyclic monosaccharide by
replacement of the hemiacetal carbon -OH group with an
-OR group.
• A glycoside produced from glucose is called a glucoside,
that from galactose is called a galactoside, and so on.
• Like the hemiacetals from which they are formed, can exist
in both α and β forms.
• In biochemical systems enzymes can oxidize the primary
• Named by listing the alkyl or aryl group attached to the
alcohol end of an aldose such as glucose, without oxidation
of the aldehyde group, to produce an alduronic acid. oxygen, followed by the name of the monosaccharide
involved, with the suffix -ide appended to it.
• For glucose, such an oxidation produces D-glucuronic
acid.
PHOSPHATE ESTER FORMATION

• The hydroxyl groups of a monosaccharide can react with
REDUCTION OF PRODUCE SUGAR ALCOHOL inorganic oxyacids to form inorganic esters.
• The carbonyl group present in a monosaccharide (either • Phosphate esters, formed from phosphoric acid and
an aldose or a ketose) can be reduced to a hydroxyl group, various monosaccharides, are commonly encountered in
using hydrogen as the reducing agent. biochemical systems.
• For aldoses and ketoses, the product of the reduction is the
corresponding polyhydroxy alcohol, which is sometimes
called a sugar alcohol.
• For example, the reduction of D-glucose gives D-glucitol.
• These phosphate esters of glucose are stable in aqueous

solution and play important roles in the metabolism of
carbohydrates.
AMINO SUGAR FORMATION
• If one of the hydroxyl groups of a monosaccharide is
replaced with an amino group, an amino sugar is
produced.
• In naturally occurring amino sugars, of which there are
three common ones, the amino group replaces the carbon
2 hydroxyl group.
• The three common natural amino sugars are D-
Glucosamine, D-Galactosamine, and D-Mannosamine.
DISACCHARIDES
• A carbohydrate in which two monosaccharides are bonded
• Amino sugars and their N-acetyl derivatives are important
together.
building blocks of polysaccharides found in chitin (Section
• In disaccharide formation, one of the monosaccharide
8.16) and hyaluronic acid.
reactants functions as a hemiacetal, and the other
• The N-acetyl derivatives of D-glucosamine and D-
functions as an alcohol.
galactosamine are present in the biochemical markers on
red blood cells, which distinguish the various blood types.
GLYCOSIDIC LINKAGE
• Is the bond in a disaccharide resulting from the reaction
between the hemiacetal carbon atom -OH group of one
monosaccharide and an -OH group on the other
monosaccharide.
• It is always a carbon–oxygen–carbon bond in a
disaccharide.
• Many disaccharides contain both a hemiacetal carbon
atom and an acetal carbon atom, as is the case for the
preceding disaccharide structure.
• The remainder of this section deals with the specifi c

structures and properties of four important disaccharides:
o maltose,
o cellobiose,
o lactose, and
o sucrose.
MALTOSE SUGAR
• Often called malt sugar, is produced whenever the
polysaccharide starch breaks down, as happens in seed
germination and in human beings during starch digestion.
• It is a common ingredient in baby foods and is found in
malted milk. Malt (germinated barley that has been baked
and ground) contains maltose.
• Structurally, maltose is made up of two D-glucose units, CELLOBIOSE
one of which must be a-D-glucose. • Is produced as an intermediate in the hydrolysis of the
polysaccharide cellulose.
• Contains two D-glucose monosaccharide units.
• It differs from maltose in that one of the D-glucose units—
the one functioning as a hemiacetal—must have a β
configuration instead of the α configuration for maltose.
• This change in configuration results in a β (1 : 4) glycosidic
linkage.
• he glycosidic linkage between the two glucose units is

called an α (1 : 4) linkage.
• The two -OH groups that form the linkage are attached,
respectively, to carbon 1 of the first glucose unit (in an α
configuration) and to carbon 4 of the second.
• Cellobiose is a reducing sugar, has three isomeric forms in

aqueous solution, and upon hydrolysis produces two D-
glucose molecules.
MALTOSE AND CELLOBIOSE

• Have different biochemical behaviors.
• These differences are related to the stereochemistry of
• Maltose is a reducing sugar because the glucose unit on their glycosidic linkages.
the right has a hemiacetal carbon atom (C-1).
• Maltase, the enzyme that breaks the glucose–glucose α(1 :
• Thus, this glucose unit can open and close; it is in 4) linkage present in maltose, is found both in the human
equilibrium with its open-chain aldehyde form. body and in yeast.
• This means there are actually three forms of the maltose • Consequently, maltose is digested easily by humans and is
molecule: a-maltose, b-maltose, and the open-chain readily fermented by yeast.
form.
• Both the human body and yeast lack the enzyme cellobiase
• In the solid state, the β form is dominant. needed to break the glucose– glucose β(1 : 4) linkage of
• The most important chemical reaction of maltose is that of cellobiose.
hydrolysis. • Thus, cellobiose cannot be digested by humans or
o Hydrolysis of D-maltose produces two molecules of fermented by yeast.
D-glucose.
• Acidic conditions or the enzyme maltase is needed for the LACTOSE
hydrolysis to occur. • Lactose is made up of a β-D-galactose unit and a D-glucose
unit joined by a β(1 : 4) glycosidic linkage.
The glucose hemiacetal center is unaffected when galactose Sucrose hydrolysis (digestion) produces an equimolar mixture
bonds to glucose in the formation of lactose, so lactose is a of glucose and fructose called invert sugar.
reducing sugar (the glucose ring can open to give an aldehyde).
• Lactose is the major sugar found in milk. This accounts for
its common name, milk sugar.
• Enzymes in mammalian mammary glands take glucose
from the bloodstream and synthesize lactose in a four-step OTHER TYPES OF GLYCOSIDIC LINKAGES
process. • Three of the four disaccharides considered in this
• Epimerization of glucose yields galactose, and then the section—maltose, cellobiose, and lactose—have (1 : 4)
β(1 : 4) linkage forms between a galactose and a glucose glycosidic linkages.
unit. • The other disaccharide considered, sucrose, has a (1 : 2)
• Lactose is an important ingredient in commercially glycosidic linkage.
produced infant formulas that are designed to simulate • Other carbon atoms besides 1, 2, and 4 can also participate
mother’s milk. in glycosidic linkages.
• Souring of milk is caused by the conversion of lactose to • An additional common type of glycosidic linkage is one
lactic acid by bacteria in the milk. that involves carbons 1 and 6.
• Pasteurization of milk is a quick-heating process that kills • Several disaccharides not detailed in this section have α-(1
most of the bacteria and retards the souring process. : 6) glycosidic linkages.
• Lactose can be hydrolyzed by acid or by the enzyme • The following structure is that for two α-D-glucose
lactase, forming an equimolar mixture of galactose and molecules connected via an α-(1 : 6) glycosidic linkage.
glucose.
SUCROSE
• Common table sugar, is the most abundant of all
disaccharides and occurs throughout the plant kingdom.
• It is produced commercially from the juice of sugar cane
and sugar beets.
o Sugar cane contains up to 20% by mass sucrose, and
o Sugar beets contain up to 17% by mass sucrose.
• The two monosaccharide units present in a D-sucrose • This disaccharide is an entirely different compound than
molecule are α-D-glucose and b-D-fructose. maltose or cellobiose, both of which involve two glucose
molecules connected, respectively, via α(1 : 4) and β(1 : 4)
• α, β(1 : 2) glycosidic linkage.
glycosidic linkages.
o The -OH group on carbon 2 of D-fructose (the
hemiacetal carbon) reacts with the -OH group on OLIGOSACCHARIDE
carbon 1 of D-glucose (the hemiacetal carbon)
• Are carbohydrates that contain three to ten
monosaccharide units bonded to each other via glycoside
linkages.
• Two naturally occurring oligosaccharides found in onions,
cabbage, broccoli, brussel sprouts, whole wheat, and all
types of beans are the trisaccharide raffinose and the
tetrasaccharide stachyose.
• Raffinose’s monosaccharide components are galactose,
glucose, and fructose.
• Stachyose’s structure differs from that of raffinose in that an
additional galactose unit is present.
• Note the presence in both structures of two different types
of glycosidic linkages—α(1 : 6) and α,β(1 : 2) linkages.
• Humans lack the digestive enzymes necessary to
metabolize either raffinose or stachyose.
• Sucrose is a nonreducing sugar. • Hence these oligosaccharides, when ingested in food, pass
• In sucrose, the hemiacetal center (anomeric carbon atom) undigested into the large intestine, where bacteria act
of each monosaccharide is involved in the glycosidic upon them (usually produces discomfort and flatulence
linkage. (gas).
• The result is a molecule that contains two acetal centers. • Beano and related products contain the enzyme (not found
• Sucrose, in the solid state and in solution, exists in only one in humans) that facilitates the digestion of these
form—there are no a and b isomers, and an open-chain oligosaccharides.
form is not possible. • The type of blood a person has (O, A, B, or AB) is
SUCRASE determined by the type of oligosaccharide that is attached
• The enzyme needed to break the α, β(1 : 2) linkage in to the person’s red blood cells.
sucrose, is present in the human body.
• Hence, sucrose is an easily digested substance.
• One of the monosaccharides present in the The arrangement of these monosaccharides in the biochemical
oligosaccharides associated with blood type is a 6-deoxy- marker determines blood type.
L-monosaccharide.
Note that all three of the oligosaccharide markers have a

common four-monosaccharide sequence in their structure.
The absence or presence of a fifth monosaccharide (attached to

the second galactose) determines blood type.
• Type O blood lacks a fifth monosaccharide unit.
• Type A blood has N-acetylgalactosamine as a fifth unit.
• Type B blood has galactose as a fifth unit.
• Type AB blood contains both type A and type B markers.
GENRAL CHARACTERISTICS OF
POLYSACCHARIDES
• A polysaccharide is a polymer that contains many
monosaccharide units bonded to each other by glycosidic
linkages.
GLYCAN
• An alternate name for a polysaccharide
IMPORTANT PARAMETERS THAT DISTINGUISH
VARIOUS POLYSACCHARIDES FROM EACH OTHER ARE:
1. The identity of the monosaccharide repeating unit(s) in the
polymer chain.
o The more abundant polysaccharides in nature
contain only one type of monosaccharide repeating
unit.
o A homopolysaccharide is a polysaccharide in
FOUR MONOSACCHARIDES CONTRIBUTE TO THE which only one type of monosaccharide monomer is
MAKE-UP OF THE OLIGOSACCHARIDE “MARKING present.
SYSTEM.” ▪ starch, glycogen, cellulose, and chitin
o A heteropolysaccharide is a polysaccharide in
which more than one (usually two) type of
monosaccharide monomer is present.
▪ hyaluronic acid and heparin
2. The length of the polymer chain.
3. The type of glycosidic linkage between monomer units.
4. The degree of branching of the polymer chain.
Unlike monosaccharides and most disaccharides,
polysaccharides are not sweet and do not test positive in Tollens
and Benedict’s solutions. Polysaccharides, such as fl our and
cornstarch, are often used as thickening agents in sauces,
desserts, and gravy.
Storage Polysaccharides Starch and glycogen
Structural cellulose and chitin

Polysaccharides
Acidic Polysaccharides hyaluronic acid and heparin
GLYCOGEN
• Is a polysaccharide containing only glucose units.
• It is the glucose storage polysaccharide in humans and
animals.
• Its function is thus similar to that of starch in plants, and it is
sometimes referred to as animal starch.
• Liver cells and muscle cells are the storage sites for
glycogen in humans.
• Similar structure with amylopectin
• All glycosidic linkages are of the α type, and both (1 : 4)
STORAGE POLYSACCHARIDES and (1 : 6) linkages are present.
• Is a polysaccharide that is a storage form for GLYCOGEN VS AMYLOPECTIN
monosaccharides and is used as an energy source in cells. • The number of glucose units between branches
• In cells, monosaccharides are stored in the form of • The total number of glucose units present in a molecule.
polysaccharides rather than as individual • Glycogen is about three times more highly branched than
monosaccharides in order to lower the osmotic pressure amylopectin, and it is much larger, with up to 1,000,000
within cells. glucose units present.
• Osmotic pressure depends on the number of individual
EXCESS GLUCOSE
molecules present.
• Most important storage polysaccharides are starch and • Present in the blood (normally from eating too much
glycogen starch)
• The liver and muscle tissue convert the excess glucose to
STARCH glycogen, which is then stored in these tissues.
• Is a homopolysaccharide containing only glucose
GLUCOSE BLOOD LEVEL DROP
monosaccharide units.
• It is the energy-storage polysaccharide in plants. • From exercise, fasting, or normal activities
• If excess glucose enters a plant cell, it is converted to • Some stored glycogen is hydrolyzed back to glucose.
starch and stored for later use. These two opposing processes are called glycogenesis and
• When the cell cannot get enough glucose from outside the glycogenolysis, the formation and decomposition of glycogen,
cell, it hydrolyzes starch to release glucose. respectively.
• Iodine is often used to test for the presence of starch in
solution.
• Starch-containing solutions turn a dark blue-black when
iodine is added.
GLYCOGEN
• As starch is broken down through acid or enzymatic
• An ideal storage form for glucose.
hydrolysis to glucose monomers, the blue-black color
disappears. • The large size of these macromolecules prevents them
from diffusing out of cells.
TWO DIFFERENT POLYGLUCOSE POLYSACCHARIDES
• Conversion of glucose to glycogen reduces osmotic
CAN BE ISOLATED
pressure.
AMYLOSE • Cells would burst because of increased osmotic pressure
• A straight-chain glucose polymer, usually accounts for if all of the glucose in glycogen were present in cells in free
15%–20% of the starch. form.
• Its non-branched structure, the glucose units are • High concentrations of glycogen in a cell sometimes
connected by α(1 : 4) glycosidic linkages. precipitate or crystallize into glycogen granules.
AMYLOPECTIN o These granules are discernible in photographs of
cells under electron microscope magnification
• A branched glucose polymer, accounts for the remaining
80%–85% of the starch. STRUCTURAL POLYSACCHARIDES
• Has a high degree of branching in its polyglucose • Is a polysaccharide that serves as a structural element in
structure. plant cell walls and animal exoskeletons.
• A branch occurs about once every 25– 30 glucose units. • Two of the most important structural polysaccharides are
• The branch points involve α(1 : 6) linkages. cellulose and chitin.
• Because of the branching, amylopectin has a larger o Both are homopolysaccharides
average molecular mass than the linear amylose.
• Up to 100,000 glucose units may be present in an
amylopectin polymer chain
CELLULOSE • All of the oligosaccharide markers that determine blood
• The structural component of plant cell walls, is the most type (Chemical Connections 18-D) contain an NAG
abundant naturally occurring polysaccharide. monosaccharide unit.
• The “woody” portions of plants have particularly high • Chitin polymers contain both glycosidic linkages and
concentrations of this fibrous, water-insoluble substance. amine bonds, both of which can be broken via hydrolysis.
• Like amylose, cellulose an unbranched glucose polymer. D-GLUCOSAMINE
• have a beta-configuration, β(1 : 4) linkages • Complete hydrolysis product of chitin.
• Marketed as a dietary supplement touted to help with joint
problems
• claims that D-glucosamine decreases joint inflammation
and pain associated with osteoarthritis have yet to be
substantiated.
SUMMARY OF GLYCOSIDIC LINKAGES IN SACCHARIDES
• Amylose molecules tend to have spiral-like structures,

whereas cellulose molecules tend to have linear
structures (water-insoluble fibers).
• Cellulose chains contain about 5000 glucose units, which
gives macromolecules with molecular masses of about
900,000 amu.
• Cellulose is not a source of nutrition for human beings.
o Humans lack the enzymes capable of catalyzing the
hydrolysis of β(1 : 4) linkages
• It serves as dietary fiber.
• Cellulose readily absorbs water, leading to softer stools
and frequent bowel action.
CELLULASE
• Produced by bacteria in the intestinal tracts of animals such
as horses, cows, and sheep.
• an enzyme that can hydrolyze cellulose b(1 : 4) linkages
and produce free glucose from cellulose.
DIETARY FIBERS
• Provides the digestive tract with “bulk” that helps move
food through the intestinal tract and facilitates the
ACIDIC POLYSACCHARIDES
excretion of solid wastes.
• Some, bind lipids such as cholesterol (Section 19.9) and • Is a polysaccharide with a disaccharide repeating unit in
carry them out of the body with the feces. which one of the disaccharide components is an amino
• About 25–35 grams of dietary fiber daily is a desirable sugar and one or both disaccharide components has a
intake. negative charge due to a sulfate group or a carboxyl
group.
CHITIN
• Are heteropolysaccharides
• The second most abundant naturally occurring o Two different monosaccharides are present in an
polysaccharide. alternating pattern.
• Its function is to give rigidity to the exoskeletons of crabs, • Two of the most well-known acidic polysaccharides are
lobsters, shrimp, insects, and other arthropods. hyaluronic acid and heparin, both of which have
• It also has been found in the cell walls of fungi. unbranched-chain structures.
• The monosaccharide present is the glucose derivative N-
HYALURONIC ACID
acetyl-D-glucosamine (NAG)
• Structure contains alternating residues of N-acetyl-β-D-
glucosamine (NAG) and D-Glucuronate.
• D-glucuronate is the carboxylate ion formed when D-
glucuronic acid loses its acidic hydrogen atom.
• D-Glucuronic acid is the product obtained when the - SIMPLE CARBOHYDRATES
CH2OH group of a glucose molecule is oxidized to a - • Is a dietary monosaccharide or dietary disaccharide.
COOH group. Simple carbohydrates are usually sweet to the taste and
• Two repeating units in the structure of hyaluronic acid are are commonly referred to as sugars.
in this structure, note the alternating pattern of glycosidic • provide 20% of the energy in the U.S. diet.
bond types, β(1 : 3) and β(1 : 4). • Half of this energy content comes from natural sugars and
the other half from refined sugars added to foods.
NATURAL SUGAR
• Is a sugar naturally present in whole foods.
• Milk and fresh fruit are two important sources of natural
sugars
• Are accompanied by nutrients
• There are approximately 50,000 disaccharide units per

REFINED SUGAR
chain. • Is a sugar that has been separated from its plant source.
• Sugar beets and sugar cane are major sources of refined
HIGHLY VISCOUS HYALURONIC ACID SOLUTIONS sugars.
• Serve as lubricants in the fluid of joints, and they are also • Are chemically and structurally no different from the
associated with the jelly-like consistency of the vitreous sugars naturally present in foods.
humor of the eye. • Provide empty calories because they provide energy but
• The Greek word hyalos means “glass”; hyaluronic acid few other nutrients.
solutions have a glass-like appearance.
The only difference is that the refined sugar is in a pure form,
HEPARIN whereas natural sugars are part of mixtures of substances
• A small highly-sulfated polysaccharide with only 15–90 obtained from a plant source.
disaccharide residues per chain.
COMPLEX CARBOHYRATES
• The monosaccharides present in heparin’s disaccharide
repeating unit are a sulfate derivative of D-glucuronate (D- • Is a dietary polysaccharide.
glucuronate-2-sulfate) and a doubly sulfated derivative of • The main complex carbohydrates are starch and cellulose,
D-glucosamine (N-sulfo-D-glucosamine-6-sulfate). substances not generally sweet to the taste.
• Both of these monosaccharide derivatives contain two • The major dietary source for complex carbohydrates in the
negatively charged acidic groups. U.S. diet is grains, a source of both starch and fiber as well
as of protein, vitamins, and minerals.
DIETARY INTAKE OF CARBOHYDRATES
glycemic response
• Refers to how quickly carbohydrates are digested (broken
down into glucose), how high blood glucose levels rise,
and how quickly blood glucose levels return to normal
• Two measurement systems called the glycemic index (GI)
and the glycemic load (GL) have been developed for
rating carbohydratecontaining foods in terms of their
• A blood anticoagulant. It is naturally present in mast cells glycemic response
and is released at the site of tissue injury.
GLYCOLIPIDS AND GLYCOPROTEINS: CELL
• It prevents the formation of clots in the blood and retards
the growth of existing clots within the blood. RECOGNITION
• It does not, however, break down clots that have already • Biochemistry of carbohydrates (prior to 1960)
formed. o As energy sources for plants, humans, and animals
and
PHARMACEUTICAL-GRADE HEPARIN
o As structural materials for plants and arthropods.
• Is applied as an anticoagulant to the interior/ exterior
• The mono-, di-, and oligosaccharides attached through
surface of external objects that come in contact with blood
glycosidic linkages to lipid molecules
(test tubes, kidney dialysis machine surfaces, prosthetic
• Protein molecules have a wide range of biochemical
implant materials) to prevent the blood from clotting.
functions
• The source is intestinal or lung tissue of slaughter-house
o Cell interaction with evading bacteria and viruses.
animals (pigs and cows).
o Cell to cell recognition
DIETARY CONSIDERATION AND GLYCOLIPID
CARBOHYDRATES • Is a lipid molecule that has one or more carbohydrate (or
• Nutritionists usually subdivide dietary carbohydrates into carbohydrate derivative) units covalently bonded to it.
the categories simple and complex. • Cerebrosides and gangliosides occur extensively in brain
tissue.
GLYCOPROTEIN
• Is a protein molecule that has one or more carbohydrate
(or carbohydrate derivative) units covalently bonded to it.
• Immunoglobins are key components of the body’s
immune system response to invading foreign materials.
CARBOHYDRATE METABOLISM
DIGESTION
• Is the biochemical process by which food molecules,
through hydrolysis, are broken down into simpler
chemical units that can be used by cells for their metabolic
needs.
• The first stage of in the processing of food products
• Begins in the mouth, where the enzyme salivary α-
amylase catalyzes the hydrolysis of α-glycosidic linkages
in starch from plants and glycogen from meats to produce
smaller polysaccharides and the disaccharide maltose.
SALIVARY-α-AMYLASE
• Inactivated by the acidic environment of the stomach, and
the stomach’s own secretions do not contain any
carbohydrate-digesting enzymes.
SMALL INTESTINE
• Primary site for carbohydrate digestion
• Where α-amylase, this time secreted by the pancreas,
again begins to function.
PANCREATIC α-AMYLASE
• Breaks down polysaccharide chains into shorter and
GLYCOLYSIS
shorter segments until the disaccharide maltose (two
• Is the metabolic pathway by which glucose (a C6
glucose units) and glucose itself are the dominant species.
molecule) is converted into two molecules of pyruvate (a
OUTER MEMBRANES OF INTESTINAL MUCOSAL CELLS C3 molecule), chemical energy in the form of ATP is
• The final step in carbohydrate digestion occurs produced, and NADH-reduced coenzymes are produced.
• Where the enzymes that convert disaccharides to • It is a linear that functions in almost all cells
monosaccharides are located. • The conversion of glucose to pyruvate is an oxidation
MALTASE, SUCRASE, AND LACTASE process in which no molecular oxygen is utilized.
o The oxidizing agent is the coenzyme NAD+.
• Important disaccharidase enzymes
• Glycolysis is an anaerobic pathway
• These enzymes convert, respectively, maltose to two
glucose units, sucrose to one glucose and one fructose unit, ANAEROBIC PATHWAYS
and lactose to one glucose and one galactose unit. • Metabolic pathways in which molecular oxygen is not a
GLUCOSE, GALACTOSE, AND FRUCTOSE participant
• Major breakdown products AEROBIC PATHWAYS

• These monosaccharides are absorbed into the • Pathways that require molecular oxygen
bloodstream through the intestinal wall.
TEN STEP PROCESS OF GLYCOLYSIS
• Fingerlike projections, Villi lined the folds of the intestinal
wall SIX-CARBON STAGE OF GLYCOLYSIS
• Absorption through Active Transport • Energy-consuming stage.
• Protein carriers mediate the passage of the • The energy release associated with the conversion of two
monosaccharides through cell membranes. ATP molecules to two ADP molecules is used to transform
• After absorption into the the bloodstream, monosaccharides into monosaccharide phosphates.
monosaccharides are transported to the liver, • The intermediates of the six-carbon stage of glycolysis are
o Where fructose and galactose are rapidly converted all either glucose or fructose derivatives in which
into compounds that are metabolized by the same phosphate groups are present.
pathway as glucose. STEP 1: PHOSPHORYLATION USING ATP
• Glycolysis is a series of ten reactions, each of which
• Formation of Glucose 6-Phosphate.
involves a different enzyme.
• Hexokinase
o An enzyme that requires Mg2+ ion for its activity,
catalyzes the reaction.
THREE-CARBON STAGE OF GLYCOLYSIS
• Energy-generating stage.
• All of the intermediates in this stage are C3-phosphates,
two of which are high-energy phosphate species
• Loss of a phosphate from these high-energy species effects
the conversion of ADP molecules to ATP molecules.
• The C3 intermediates in this stage of glycolysis are all
• Phosphorylation of glucose provides a way of “trapping” phosphorylated derivatives of dihydroxyacetone,
glucose within a cell. glyceraldehyde, glycerate, or pyruvate, which in turn are
• Glucose can cross cell membranes, but glucose 6- derivatives of either glycerol or acetone.
phosphate cannot.
• Phosphorylation of glucose changes it from a neutral
molecule to a negatively charged substance; charge
severely limits the ability of phosphorylated molecules to
cross cell membranes.
STEP 2: ISOMERIZATION
• Formation of Fructose 6-Phosphate.
• Glucose 6-phosphate is isomerized to fructose 6-
phosphate by phosphoglucoisomerase.
• The net result of this change is that carbon 1 of glucose is

no longer part of the ring structure.
STEP 3: PHOSPHORYLATION USING ATP
• Formation of Fructose 1,6-Bisphosphate.
• Phosphofructokinase
o Is another enzyme that requires Mg2+ ion for its
activity.
• The fructose molecule now contains two phosphate STEP 4: CLEAVAGE
groups. • Formation of Two Triose Phosphates
• C6 species is split into two C3 (triose) species.
• Because fructose 1,6- bisphosphate, the molecule being
split, is unsymmetrical, the two trioses produced are not
identical.
o dihydroxyacetone phosphate
o glyceraldehyde 3-phosphate
• Aldolase is the enzyme that catalyzes this reaction.
• Formation of Glyceraldehyde 3-Phosphate.
• Only glyceraldehyde 3-phosphate (aldose), is a glycolysis
intermediate.
• Dihydroxyacetone phosphate (ketose) can be readily
converted into glyceraldehyde 3-phosphate.
• Isomerization process from ketose to aldose is catalyzed
by the enzyme triosephosphate isomerase.
• The enzyme phosphoglyceromutase catalyzes the
exchange of the phosphate group between the two
carbons
STEP 6: OXIDATION AND PHOSPHORYLATION USING Pi

• Formation of 1,3-Bisphosphoglycerate
• Reaction catalyzed by glyceraldehyde 3-phosphate STEP 9: DEHYDRATION
dehydrogenase, • Formation of Phosphoenolpyruvate.
o A phosphate group is added to glyceraldehyde 3- • This is an alcohol dehydration reaction that proceeds with
phosphate to produce 1,3-bisphosphoglycerate. the enzyme enolase, another Mg2+-requiring enzyme.
• 1,3-bisphosphoglycerate • The result is another compound containing a high-energy
o A high-energy phosphate group. phosphate group.
▪ Produced when a phosphate group is attached
to a carbon atom that is also participating in a
carbon–carbon or carbon–oxygen double
bond
• The hydrogen of the aldehyde group becomes part of
NADH.
STEP 10: PHOSPHORYLATION OF ADP

• Formation of Pyruvate.
• Substrate-level phosphorylation again occurs.
Note that a molecule of the reduced coenzyme NADH is a product • Phosphoenolpyruvate transfers its high-energy phosphate
of this reaction and also that the source of the added phosphate group to an ADP molecule to produce ATP and pyruvate
is inorganic phosphate (Pi). • The enzyme involved, pyruvate kinase, requires both
STEP 7: PHOSPHORILATION OF ADP Mg2+ and K+ ions for its activity.
• Formation of 3-Phosphoglycerate
• Diphosphate species just formed is converted back to a
monophosphate species.
• This is an ATP-producing step
• The enzyme involved is phosphoglycerokinase
Remember that two ATP molecules are produced for each

original glucose molecule because both C3 molecules produced
from the glucose react.
• Substrate-Level Phosphorylation
o Is the biochemical process whereby ATP is produced
from ADP through direct transfer of a high-energy
phosphoryl group from a reaction substrate to ADP
• Oxidative Phosphorylation
o Involves production of ATP from ADP using Pi (free
phosphate) and the energy “harvested” from the
oxidation-reduction reactions of the electron
transport chain.
• Formation of 2-Phosphoglycerate
• The phosphate group of 3-phosphoglycerate is moved
from carbon 3 to carbon 2.
The net overall equation for the process of glycolysis is • A high ATP concentration, which is characteristic of a state
of low energy consumption, thus stops glycolysis at the
fructose 6-phosphate stage.
• This stoppage also causes increases in glucose 6-
phosphate stores because glucose 6-phosphate is in
equilibrium with fructose 6-phosphate.
LAST STEP
• The third control point, the conversion of
phosphoenolpyruvate to pyruvate.
• Pyruvate kinase, the enzyme needed at this point, is
inhibited by high ATP concentrations.
ENTRY OF GALACTOSE AND FRUCTOSE INTO GLYCOLYSIS
• Both pyruvate kinase (Step 10) and phosphofructokinase
• The breakdown products from carbohydrate digestion are (Step 3) are allosteric enzymes
glucose, galactose, and fructose.
• Both galactose and fructose are converted, in the liver, to
FATES OF PYRUVATE
intermediates that enter into the glycolysis pathway. • Three common fates for pyruvate, all of importance, exist.
Conversion to Formation requires aerobic (oxygen-

acetyl CoA rich) conditions.
Conversion to Formation occurs under anaerobic

lactate (oxygen-deficient) conditions.
Conversion to Limited to some microorganisms.

ethanol (Anaerobic)
• A key concept in considering these fates of pyruvate is the

need for a continuous supply of NAD+ for glycolysis.
• As glucose is oxidized to pyruvate in glycolysis, NAD+ is
reduced to NADH.
• It is significant that each of the three pathways for

processing pyruvate have a provision for regenerating
NAD+ from NADH so that glycolysis can continue.
OXIDATION TO ACETYL CoA
• The entry of galactose into the glycolytic pathway begins • Pyruvate is oxidized to acetyl CoA.
with its conversion to glucose 1-phosphate (a four-step • Pyruvate formed in the cytosol through glycolysis crosses
sequence), which is then converted to glucose 6- the two mitochondrial membranes and enters the
phosphate, a glycolysis intermediate. mitochondrial matrix, where the oxidation takes place.
• The entry of fructose into the glycolytic pathway involves
phosphorylation by ATP to produce fructose 1-phosphate,
which is then split into two trioses— glyceraldehyde and
dihydroxyacetone phosphate.
• Dihydroxyacetone phosphate enters glycolysis directly;
glyceraldehyde must be phosphorylated by ATP to
glyceraldehyde 3-phosphate before it enters the pathway.
REGULATION OF GLYCOLYSIS
• Glycolysis, like all metabolic pathways, must have control
mechanisms associated with it. In glycolysis, the control
points are Steps 1, 3, and 10 • Most acetyl CoA molecules produced from pyruvate enter
STEP 1 the citric acid cycle.
• The conversion of glucose to glucose 6-phosphate, • Citric acid cycle operations change more NAD+ to its
involves the enzyme hexokinase. reduced form, NADH.
• This particular enzyme is inhibited by glucose 6- • The NADH from glycolysis, from the conversion of
phosphate, the substance produced by its action pyruvate to acetyl CoA, and from the citric acid cycle
enters the electron transport chain directly and indirectly
(feedback inhibition).
• The net overall reaction for processing one glucose
STEP 3 molecule to two molecules of acetyl CoA is
• Where fructose 6-phosphate is converted to fructose 1,6-
bisphosphate by the enzyme phosphofructokinase, high
concentrations of ATP and citrate inhibit enzyme activity.
FERMENTATION PROCESSES
• When the body becomes oxygen deficient (anaerobic
conditions), such as during strenuous exercise, the ETHANOL FERMENTATION
electron transport chain process slows down because its • Is the enzymatic anaerobic conversion of pyruvate to
last step is dependent on oxygen. ethanol and carbon dioxide.
o A buildup in NADH concentration and a decreased • Possess the ability to regenerate NAD+ through ethanol,
amount of available NAD+ concentration. rather than lactate, production.
FERMENTATION • Fermentation involving yeast causes bread and related
• Is a biochemical process by which NADH is oxidized to products to rise as a result of CO2 bubbles being released
NAD+ without the need for oxygen during baking.
• Two fermentations: FIRST STEP
LACTATE FERMENTATION • A decarboxylation reaction to produce acetaldehyde
• Is the enzymatic anaerobic reduction of pyruvate to lactate.
SECOND STEP
• The conversion of NADH to NAD+ • acetaldehyde reduction to produce ethanol.
• The lactate so formed is converted back to pyruvate when
aerobic conditions are again established in a cell.
• Lactate structure resembles that of pyruvate and also
glycerate.
o all derivatives of propionic acid, the three-carbon
unsaturated monocarboxylic acid.
• The overall equation for the conversion of pyruvate to
ethanol (the sum of the two steps) is
• An overall reaction for the production of ethanol from

glucose is obtained by combining the reaction for the
conversion of pyruvate with the net reaction for glycolysis
Note that NADH and NAD+ do not appear in the final equation;
• Purpose of its formation is to replenish NAD+ supplies
they are both generated and consumed.
• Lactate buildup contributes to muscle soreness, muscle

cramping, and fatigue.
• The net equation for glycolysis is
• The net equation for conversion of pyruvate to lactate is
• Adding the two equation; one glucose produces two

pyruvates and therefore two lactates, yields the following
equation for the overall conversion of glucose to lactate.
GLYCOGEN SYNTHESIS AND DEGREGATION STEP 3: LINKAGE TO CHAIN
GLYCOGEN • Glucose Transfer to a Glycogen Chain.
• The glucose unit of UDP-glucose is then attached to the end
• A branched polymeric form of glucose, is the storage form
of a glycogen chain.
of carbohydrates in humans and animals.
• It is found primarily in muscle and liver tissue.
o In muscles, it is the source of glucose needed for
glycolysis.
o In the liver, it is the source of glucose needed to
maintain normal glucose levels in the blood In a subsequent reaction, the UDP produced in Step 3 is
GLYCOGENESIS converted back to UTP, which can then react with another
• Is the metabolic pathway by which glycogen is synthesized glucose 1-phosphate (Step 2). The conversion reaction requires
from glucose 6-phosphate. ATP
• Glycogenesis involves three reactions (steps).
Adding a single glucose unit to a growing glycogen chain
• Formation of Glucose 1-phosphate. requires the investment of two ATP molecules: one in the
• The starting material is glucose 6-phosphate (available formation of glucose 6-phosphate and one in the regeneration of
from the first step of glycolysis). UTP.
• The enzyme phosphoglucomutase effects the change
from a 6-phosphate to a 1-phosphate. GLYCOGENOLYSIS
• Is the metabolic pathway by which glucose 6-phosphate is
produced from glycogen.
• It does not require UTP or UDP molecules.
• Glycogenolysis is a two-step process
STEP 1: PHOSPHOROLYSIS
• Formation of Glucose-1-phosphate.
• The enzyme glycogen phosphorylase effects the removal
of an end glucose unit from a glycogen molecule as
glucose 1-phosphate.
STEP 2: ACTIVATION
• Formation of UDP-glucose.
• Glucose 1-phosphate from Step 1 must be activated before
it can be added to a growing glycogen chain.
• The activator is the high-energy compound UTP (uridine
triphosphate). • Formation of Glucose 6-phosphate.
• A UMP is transferred to glucose 1-phosphate, and the • The enzyme phosphoglucomutase catalyzes the
resulting PPi is hydrolyzed to 2Pi . isomerization process whereby the phosphate group of
glucose 1-phosphate is moved to the carbon 6 position.
Reverse process of the 1st step of glycogenesis
GLUCONEOGENESIS
• Is the metabolic pathway by which glucose is synthesized
from non-carbohydrate materials.
• Glycogen stores in muscle and liver tissue are depleted
within 12–18 hours of fasting or in even less time from
heavy work or strenuous exercise.
• The noncarbohydrate starting materials for
gluconeogenesis are
o Lactate (from hard-working muscles and from red • In Steps 9 and 11 of gluconeogenesis (Steps 1 and 3 of
blood cells), glycolysis), he reactant–product combinations match
o Glycerol (from triacylglycerol hydrolysis), and between pathways.
o Certain amino acids (from dietary protein • The new enzymes for gluconeogenesis are fructose 1,6-
hydrolysis or from muscle protein during starvation) bisphosphatase and glucose 6-phosphatase.
• 90% of gluconeogenesis takes place in the liver.
• Helps to maintain normal blood-glucose levels in times of
inadequate dietary carbohydrate intake (such as between
meals). CORI CYCLE
GLUCONEOGENESIS VS GLYCOLYSIS • Is a cyclic biochemical process in which glucose is
• The processes of gluconeogenesis (pyruvate to glucose) converted to lactate in muscle tissue, the lactate is
and glycolysis (glucose to pyruvate) are not exact reconverted to glucose in the liver, and the glucose is
opposites. returned to the muscle tissue.
• The slow rate of the reaction • Gluconeogenesis using lactate as a source of pyruvate is
particularly important because of lactate formation during
strenuous exercise.
• The lactate so produced diffuses from muscle cells into the
blood, where it is transported to the liver.
• Here the enzyme lactate dehydrogenase (the same
enzyme that catalyzes lactate formation in muscle)
converts lactate back to pyruvate.
• A two-step process by way of oxaloacetate is required to
effect the change, and this adds an extra compound to the
gluconeogenesis pathway.
• Both an ATP molecule and a GTP molecule are needed to
drive this two-step process.
• The newly formed pyruvate is then converted via

gluconeogenesis to glucose, which enters the bloodstream
and goes to the muscles.
• A net loss of nucleotide triphosphates (ATP, GTP)
accompanies Cori cycle operation.
TERMINOLOGY FOR GLUCOSE METABOLIC
PATHWAYS
• There are two other locations where gluconeogenesis and

glycolysis differ.
• The glycogen degradation pathways have names ending

in -lysis, which means “breakdown.”
• The pathways associated with glycogen synthesis names
ending in -genesis, which means “making.”
• The net equation for the oxidative stage of the pentose
phosphate pathway is
Note the production of two NADPH molecules per glucose 6-

phosphate processed during this stage.
NONOXIDATIVE STAGE
• First step, ribulose 5-phosphate (a ketose) is isomerized to
ribose 5-phosphate (an aldose).
PENTOSE PHOSPHATE PATHWAY

• Is the metabolic pathway by which glucose is used to
produce NADPH, ribose 5-phosphate (a pentose
phosphate), and numerous other sugar phosphates.
• Main focus is not subsequent ATP production as is the case
for glycolysis
• The pentose ribose is a component of ATP, GTP, UTP, CoA,
• Major Functions NAD+/NADH, FAD/FADH2, and RNA.
o Synthesis of the coenzyme NADPH needed in lipid
• Further step, contain provision for the conversion of ribose
biosynthesis and
5-phosphate to numerous other sugar phosphates.
o Production of ribose 5-phosphate, a pentose
Ultimately, glyceraldehyde 3-phosphate and fructose 6-
derivative needed for the synthesis of nucleic acids
phosphate (both glycolysis intermediates) are formed.
and many coenzymes.
• The overall net reaction for the pentose phosphate
• Significant in cells that produce lipids: fatty tissue, the
pathway is
liver, mammary glands, and the adrenal cortex (an active
producer of steroid lipids).
NADPH
THE PENTOSE PHOSPHATE PATHWAY HELPS MEET
• The coenzyme produced in the pentose phosphate CELLULAR NEEDS IN NUMEROUS WAY:
pathway, is the reduced form of NADP+ (nicotinamide
(1) When ATP demand is high, the pathway continues to its
adenine dinucleotide phosphate).
end products, which enter glycolysis.
• Structurally, NADP+/NADPH is a phosphorylated version of (2) When NADPH demand is high, intermediates are recycled
NAD+/NADH. to glucose 6-phosphate (the start of the pathway), and
further NADPH is produced.
(3) When ribose 5-phosphate demand is high, for nucleic acid
and coenzyme production, most of the nonoxidative stage
is nonfunctional, leaving ribose 5-phosphate as a major
product.
SUMMARY OF GLUCOSE METABOLISM
NONPHOSPHORYLATED VERSION
• Involved, mainly in its oxidized form (NAD+), in the
reactions of the common metabolic pathway
PHOSPHORYLATED VERSION
• Involved, mainly in its reduced form (NADPH), in
biosynthetic reactions of lipids and nucleic acids.
TWO STAGES WITHIN THE PENTOSE PHOSPHATE
PATHWAY
OXIDATIVE STAGE
• Occurs first, involves three steps through which glucose 6-
phosphate is converted to ribulose 5-phosphate and CO2.
26  CARBOHYDRATES AND CARBOHYDRATES METABOLISM
HORMONAL CONTROL OF CARBOHYDRATES • Four of the six B vitamins involved in carbohydrate
metabolism are the same four that are involved in the
• A second major method for regulating carbohydrate
common metabolic pathway.
metabolism
o Niacin (as NAD+, NADH),
• Three hormones that affect carbohydrates:
o Riboflavin (as FAD),
INSULIN o Thiamin (as TPP), and
• A 51-amino-acid protein hormone is produced by the beta o Pantothenic acid (as CoA).
cells of the pancreas. The two newly involved B vitamins are biotin and vitamin B6:
• promotes the uptake and utilization of glucose by cells. (1) Biotin involvement occurs in the enzyme pyruvate
• Thus, its function is to lower blood-glucose levels. carboxylate, the enzyme needed to convert pyruvate to
• It is also involved in lipid metabolism. oxaloacetate (the new first step in gluconeogenesis).
• Also produces an increase in the rates of glycogenesis, (2) Vitamin B6 in the form of PLP is involved in glycogenosis
glycolysis, and fatty acid synthesis.
DIABETES
• Metabolic disorder
• Either the body does not produce enough insulin or body
cells do not respond properly to the insulin that is
produced.
GLUCAGON
• Is a polypeptide hormone (29 amino acids) produced in the
pancreas by alpha cells.
• It is released when blood-glucose levels are low.
• Its principal function is to increase blood-glucose
concentrations by speeding up the conversion of glycogen
to glucose (glycogenolysis) and gluconeogenesis in the
liver.
• Thus, glucagon’s effects are opposite those of insulin.
EPINEPHRINE
GLYCOGEN STORAGE DISORDER
• Also called adrenaline, is released by the adrenal glands
in response to anger, fear, or excitement. GSD TYPE NAME ENZYME DEFICIENT
• Its function is similar to that of glucagon— stimulation of
1 Von Gierke’s Gluc-6-phosphate
glycogenolysis, the release of glucose from glycogen.
• Its primary target is muscle cells, where energy is needed 2 Pompe’s α-glucosidase
for quick action. 3 Cori Debranching
• It also functions in lipid metabolism.
4 Andersen Branching
• Stimulate the enzyme adenyl cyclase to begin production
of a second messenger, cyclic AMP (cAMP) from ATP. 5 McArdle’s Muscle phosphorylase
• The cAMP is released in the cell interior, where, in a series 6 Hers Liver phosphorylase
of reactions, it activates glycogen phosphorylase, the
enzyme that initiates glycogenolysis. 7 Tarui Phosphofructokinase
• Cyclic AMP also inhibits glycogenesis, thus preventing
glycogen production at the same time. PROTEINS
• Is a naturally occurring, unbranched polymer in which the
monomer units are amino acids.
• Next to water, proteins are the most abundant substances
in nearly all cells—they account for about 15% of a cell’s
overall mass and for almost half of a cell’s dry mass.
• All proteins contain the elements carbon, hydrogen,
oxygen, and nitrogen; most also contain sulfur.
• The presence of nitrogen in proteins sets them apart
• The average nitrogen content of proteins is 15.4% by mass.
Other elements, such as phosphorus and iron, are essential
B VITAMINS AND CARBOHYDRATE METABOLISM constituents of certain specialized proteins.
• Major function is that of the coenzymes in metabolic CASEIN

reactions. • The main protein of milk, contains phosphorus, an element
• B vitamin involvement in the processes of glycolysis, very important in the diet of infants and children.
gluconeogenesis, glycogenesis, glycogenolysis, and HEMOGLOBIN
conversion of pyruvate to acetyl CoA and lactate.
• The oxygen-transporting protein of blood, contains iron.
• Six of the eight B vitamins are involved in carbohydrate
metabolism.
27  PROTEINS AND PROTEINS METABOLISM
AMINO ACIDS: BUILDING BLOCKS FOR o Serine o Asparagine
PROTEINS o Cysteine o Glutamine
o Threonine o Tyrosine
AMINO ACID
• Is an organic compound that contains both an amino (-NH2)
group and a carboxyl (-COOH) group.
• Always α-amino acid
o Is an amino acid in which the amino group and the
carboxyl group are attached to the a-carbon atom.
AMINO ACID SIDE CHAIN

• The R group present in an a-amino acid
• The nature of this side chain distinguishes α-amino acids
from each other.
• Side chains vary in size, shape, charge, acidity, functional
groups present, hydrogen-bonding ability, and chemical
reactivity.
STANDARD AMINO ACIDS POLAR ACIDIC AMINO ACIDS
• Is one of the 20 a-amino acids normally found in proteins. • Is an amino acid that contains one amino group and two
• This classification system gives insights into how various carboxyl groups, the second carboxyl group being part of
types of amino acid side chains help determine the the side chain.
properties of proteins • Bears a negative charge; the side-chain carboxyl group
has lost its acidic hydrogen atom.
NONPOLAR AMINO ACIDS • Two Carboxylic
• Is an amino acid that contains one amino group, one • Two polar acidic amino acids
carboxyl group, and a nonpolar side chain. o Aspartic Acid
• Hydrophobic (“water-fearing”) o Glutamic Acid.
• Nine nonpolar amino acids
o Glycine o Proline
o Alanine o Phenylalanine
o Valine o Methionine
o Leucine o Tryptophan
o Isoleucine
POLAR BASIC AMINO ACIDS

• Is an amino acid that contains two amino groups and one
carboxyl group, the second amino group being part of the
side chain.
• Bears a positive charge; the nitrogen atom of the amino
group has accepted a proton.
• Two Amine
• Three polar basic amino acids:
o Lysine o Histidine
• Tryptophan is a borderline member of this group because o Arginine
water can weakly interact through hydrogen bonding with
the NH ring location on tryptophan’s side-chain ring
structure
POLAR NEUTRAL AMINO ACIDS
• Is an amino acid that contains one amino group, one
carboxyl group, and a side chain that is polar but neutral.
• Hydrophilic (“water-loving”).
• Six polar neutral amino acids.
THEORIES OF ACID AND BASE INCOMPLETE DIETARY PROTEIN
THEORY ACID BASE • Is a protein that does not contain adequate amounts,
relative to the body’s needs, of one or more of the essential
Arrhenius H+ in H2O OH- in H2O amino acids.
Bronsted Lowry H+ Donor H+ Acceptor • Common in animal
o Gelatin - a protein in which tryptophan is the limiting
Lewis Accept e- Donate e- amino acid
• Plant sources
STANDARD AMINO ACIDS
LIMITING AMINO ACID
• Names are often abbreviated using three letter codes.
• Except in four cases, these abbreviations are the first three • Is an essential amino acid that is missing, or present in
letters of the amino acid’s name. inadequate amounts, in an incomplete dietary protein.
• One-letter code for amino acid names exists that is o Lysine (wheat, rice, oats, and corn),
particularly useful in computer applications that involve o Methionine (beans and peas), and
proteins. o Tryptophan (corn and beans).
• 10 essential amino acids COMPLEMENTARY DIETARY PROTEINS
o The adult human body cannot produce adequate • Are two or more incomplete dietary proteins that, when
amounts of the other nine standard amino acids. combined, provide an adequate amount of all essential
amino acids relative to the body’s needs.
• Rice, beans or corn
CHIRALITY AND AMINO ACIDS
• Four different groups are attached to the a-carbon atom in
all of the standard amino acids except glycine, where the
R group is a hydrogen atom
• 19 of 20 amino acids have chiral center

• The amino acids found in nature and in proteins are L
isomers (preferred form)
o monosaccharides the D isomer is preferred.
THE RULES FOR DRAWING FISCHER PROJECTION
FORMULAS OF AMINO ACIDS
• The -COOH group is put at the top of the projection
formula, the R group at the bottom. This positions the
ESSENTIAL AMINO ACIDS carbon chain vertically.
• The -NH2 group is in a horizontal position. Positioning it on
• Is a standard amino acid needed for protein synthesis that
the left denotes the L isomer, and positioning it on the right
must be obtained from dietary sources because the human
denotes the D isomer
body cannot synthesize it in adequate amounts from other
substances.
• There are nine essential amino acids for adults, and a tenth
one is needed for growth in children.
o Arginine o Methionine
o Histidine o Phenylalanine
o Isoleucine o Threonine
o Leucine o Tryptophan ACID-BASE PROPERTIES OF AMINO ACIDS
o Lysine o Valine
• In pure form, amino acids are white crystalline solids with
Arginine is required for growth in children but is not essential relatively high decomposition points.
for adults o Most amino acids decompose before they melt
COMPLETE DIETARY PROTEIN
• Is a protein that contains all of the essential amino acids in
the same relative amounts in which the body needs them.
• May or may not contain all of the nonessential amino acids.
• Animal sources
o Casein • In neutral solution, carboxyl groups have a tendency to
• Soy is the only common plant protein that is a complete lose protons (H+), producing a negatively charged
dietary protein species:
−𝑪𝑶𝑶𝑯 → −𝑪𝑶𝑶− + 𝑯+
• In neutral solution, amino groups have a tendency to
accept protons (H+), producing a positively charged
species:
−𝑵𝑯𝟐 + 𝑯+ → −𝑵𝑯𝟑
• The -COOH group of an amino acid donates a proton to the
-NH2 of the same amino acid. ISOELECTRIC PAIRS
• We can characterize this behavior as an internal acid–
• Is the pH at which an amino acid exists primarily in its
base reaction. zwitterion form.
ZWITTERION • At the isoelectric point, almost all amino acid molecules in
• German term meaning “double ion.” a solution (more than 99%) are present in their zwitterion
• Is a molecule that has a positive charge on one atom and a form.
negative charge on another atom, but which has no net • Those with nonpolar or polar neutral side chains, have
charge. isoelectric points in the range of 4.8–6.3.
• In an acidic solution, the zwitterion accepts a proton (H+) to • The three basic amino acids have higher isoelectric points,
form a positively charged ion. and the two acidic amino acids have lower ones.
NAME ISOELECTRIC NAME ISOELECTRIC

POINT POINT
Alanine 6.01 Leucine 5.98

Arginine 10.76 Lysine 9.74
Asparagine 5.41 Methionine 5.74
• In basic solution, the -NH3 of the zwitterion loses a proton,
and a negatively charged species is formed. Aspartic acid 2.77 Phenylalanine 5.48
Cysteine 5.07 Proline 6.48
Glutamic acid 3.22 Serine 5.68
Glutamine 5.65 Threonine 5.87
Glycine 5.97 Tryptophan 5.88
Histidine 7.59 Tyrosine 5.66
• Thus, in solution, three different amino acid forms can exist
(zwitterion, negative ion, and positive ion). Isoleucine 6.02 Valine 5.97
o Equilibrium with each other, and the equilibrium
CYSTEINE: A CHEMICALLY UNIQUE AMINO
shifts with pH change
• The overall equilibrium process can be represented as ACIDS
follows: • The only standard amino acid that has a side chain that
contains a sulfhydryl group (-SH group).
• In the presence of mild oxidizing agents, readily
dimerizes, that is, reacts with another cysteine molecule to
form a cystine molecule.
• A dimer is a molecule that is made up of two like subunits
• In cystine, the two cysteine residues are linked via a
In acidic solution, the positively charged species on the left covalent disulfide bond.
predominates; nearly neutral solutions have the middle species
(the zwitterion) as the dominant species; in basic solution, the
negatively charged species on the right predominates.
• The covalent disulfide bond of cystine is readily broken,

using reducing agents, to regenerate two cysteine
molecules.
PEPTIDES
• Is an unbranched chain of amino acids.
• Extra site that can be protonated or deprotonated, acidic • Peptides are further classified by the number of amino
and basic amino acids have four charged forms in solution. acids present in the chain
• These four forms for aspartic acid, one of the acidic amino o A compound containing two amino acids is
acids, are specifically called a dipeptide;
o three amino acids joined together in a chain
constitute a tripeptide; and so on.
o The name oligopeptide is loosely used to refer to
peptides with 10 to 20 amino acid residues,
o A polypeptide is a long unbranched chain of amino
acids.
NATURE OF THE PEPTIDE BOND
• The bonds that link amino acids together in a peptide chain
is called peptide bond.
• The repeating sequence of peptide bonds and α-carbon
• There are four peptide bonds present in a pentapeptide.
-CH groups in a peptide is referred to as the backbone of
the peptide.
• The R group side chains are considered substituents on the
backbone rather than part of the backbone.
• The reaction between a carboxylic acid and an amine to

produce an amide was considered.
• The general equation for this reaction was
PEPTIDE NOMENCLATURE
• Small peptides are named as derivatives of the C-terminal
• Two amino acids can combine in a similar way—the amino acid that is present.
carboxyl group of one amino acid interacts with the amino • The IUPAC rules for doing this are:
group of the other amino acid. RULE 1:
• The products are a molecule of water and a molecule
• The C-terminal amino acid residue (located at the far right
containing the two amino acids linked by an amide bond.
of the structure) keeps its full amino acid name.
RULE 2:
• All of the other amino acid residues have names that end in
-yl. The -yl suffi x replaces the -ine or -ic acid ending of the
amino acid name, except for tryptophan (tryptophyl),
• Removal of the elements of water from the reacting
cysteine (cysteinyl), glutamine (glutaminyl), and
carboxyl and amino groups and the ensuing formation of
asparagine (asparaginyl).
the amide bond are better visualized when expanded
structural formulas for the reacting groups are used. RULE 3:
• The amino acid naming sequence begins at the N-terminal
amino acid residue
ISOMERIC PEPTIDES
• Peptides that contain the same amino acids but in different
order are different molecules (constitutional isomers) with
different properties.
PEPTIDE BOND • For example, two different dipeptides can be formed from
one molecule of alanine and one molecule of glycine.
• Is a covalent bond between the carboxyl group of one
amino acid and the amino group of another amino acid.
• The end with the free H3N group is called the N-terminal
end, and the end with the free COO- group is called the C-
terminal end.
• The sequence of amino acids in a peptide is written with
the N-terminal end amino acid on the left BIOCHEMICALLY IMPORTANT SMALL PEPTIDES
SMALL PEPTIDE HORMONES
• The two best-known peptide hormones, both produced by
AMINO ACID RESIDUE the pituitary gland, are oxytocin and vasopressin.
• Is the portion of an amino acid structure that remains, after • Each hormone is a nonapeptide (nine amino acid residues)
the release of H2O, when an amino acid participates in with six of the residues held in the form of a loop by a
peptide bond formation as it becomes part of a peptide disulfide bond formed from the interaction of two cysteine
chain. residues.
• Structurally, these nonapeptides differ in the amino acid
present in positions 3 and 8 of the peptide chain.
• In both structures, an amine group replaces the C-terminal
single-bonded oxygen atom.
• More than one peptide chain may be present in a protein.
On this basis, proteins are classified as monomeric or
multimeric.
MONOMERIC PROTEIN
• Is a protein in which only one peptide chain is present.
MULTIMERIC PROTEIN
• Is a protein in which more than one peptide chain is
OXYTOCIN
present.
• Regulates uterine contractions and lactation • Large proteins, those with many amino acid residues,
• Leucine and Isoleucine usually are multimeric.
VASOPRESSIN PROTEIN SUBUNITS
• regulates the excretion of water by the kidneys; it also • The peptide chains present in multimeric proteins are
affects blood pressure.
• Another name is antidiuretic hormone (ADH).
• name relates its function in the kidneys, which is to
decrease urine output in order to decrease water
elimination from the body.
• Arginine and Phenylalanine
SMALL PEPTIDE NEUROTRANSMITTERS
ENKEPHALINS
• Are pentapeptide neurotransmitters produced by the
brain itself that bind at receptor sites in the brain to reduce
pain.
•
• two best-known enkephalins are Met-enkephalin and Leu-
enkephalin, whose structures differ only in the amino acid
residue present at the C-terminal end of the peptide.
• Have pain-reducing effects; short term pain relief

o Morphine-codeine pain relief lasts much longer
• Enzymes present in the brain readily hydrolyze the
peptide linkages in enkephalins; morphine and codeine
do not have such linkages and are unaffected by the
hydrolysis enzymes.
SMALL PEPTIDE ANTIOXIDANT
GLUTATHIONE (GLU–CYS–GLY)
• Present in significant concentrations in most cells and is of BASED ON CHEMICAL COMPOSITION
considerable physiological importance as a regulator of SIMPLE PROTEIN
oxidation–reduction reactions. • Is a protein in which only amino acid residues are present.
• Function as an antioxidant
CONJUGATED PROTEIN
• Is a protein that has one or more non-amino acid entities
present in its structure in addition to one or more peptide
chains.
PROSTHETIC PROTEIN
• Is a non-amino acid group present in a conjugated protein.
GENERAL STRUCTURAL CHARACTERISTICS OF CONJUGATED PROTEIN CLASSIFICATION BASED ON
PROTEIN THE NATURE OF PROSTHETIC PROTEIN PRESENT
• Lipoproteins contain lipid prosthetic groups,
• A protein is a peptide in which at least 40 amino acid
• Glycoproteins contain carbohydrate groups,
residues are present.
• Metalloproteins contain a specific metal, and so on
• The defining line governing the use of the term protein—
40 amino acid residues—is an arbitrary line. PRIMARY STRUCTURE OF PROTEIN
• The terms polypeptide and protein are often used • Is the order in which amino acids are linked together in a
interchangeably; a protein is a relatively long protein.
polypeptide. • Involves the order of attachment of the amino acids to each
• Term protein is reserved for peptides with a large number other through peptide bonds.
of amino acids
FREDERICK SANGER (BRITISH BIOCHEMISTRY) RIGIDITY OF PLANAR PEPTIDE LINKAGE STRUCTURE
• The “sequencing” of its 51 amino acids was completed in • Which means that rotation of groups about the C-N bond is
1953 of insulin primary structure; after eight years of work. hindered, and cis–trans isomerism is possible about this
• There are 1.55 x 1066 sequences possible for the 51 amino bond.
acids found in insulin (hormone that regulate glood- • The trans isomer orientation is the preferred orientation,
glucose levels) as shown in the preceding diagram.
PRIMARY STRUCTURE OF MYOGLOBIN • The O atom of the C"O group and the H atom of the N9H
group are positioned trans to each other.
• Myoglobin – a protein involved in oxygen transport in
muscle.
SECONDARY STRUCTURE OF PROTEINS

• Is the arrangement in space adopted by the backbone
portion of a protein.
APLHA HELIX
• Is a protein secondary structure in which a single protein
chain adopts a shape that resembles a coiled spring
(helix), with the coil configuration maintained by hydrogen
bonds.
FURTHER DETAILS ABOUT ALPHA HELIX SECONDARY
PROTEIN STRUCTURE ARE:
1. The twist of the helix forms a right-handed, or clockwise,
spiral.
2. The hydrogen bonds between C=O and N-H entities are
orientated parallel to the axis of the helix.
3. A given hydrogen bond involves a C=O group of one
amino acid and a N-H group of another amino acid located
four amino acid residues further along the spiral. This is
because one turn of the spiral includes 3.6 amino acid
residues.
4. All of the amino acid R groups extend outward from the
spiral There is not enough room for the R groups within the
A representative segment of a protein backbone is as follows: spiral.
BETA PLEATED SHEET
• Is a protein secondary structure in which two fully
extended protein chain segments in the same or different
molecules are held together by hydrogen bonds.
• The carbon and nitrogen atoms of a protein backbone are • Pleated = zigzag pattern
arranged in a “zigzag” manner.
• This zigzag pattern arises from the geometric
characteristics of peptide bonds.
• Important points concerning peptide bond geometry are:
THE PEPTIDE LINKAGES ARE ESSENTIALLY PLANAR.
• This means that for two amino acids linked through a
peptide linkage, six atoms lie in the same plane: the a-
carbon atom and the C=O group from the first amino acid
and the N-H group and the a-carbon atom from the second
amino acid.
• Hydrogen bonds form between oxygen and hydrogen • Major distinction between secondary and tertiary:
peptide linkage atoms that are either: o Tertiary-structure interactions involve the R groups
o Intrachain bonds of amino acids
▪ Different parts of a single chain that folds o Secondary-structure interactions involve the
back on itself. peptide linkages between amino acid residues.
o Interchain bonds
FOURBONDS
▪ Between atoms in different peptide chains in
those proteins that contain more than one
chain
FURTHER FEATURES OF THE B PLEATED SHEET

SECONDARY PROTEIN STRUCTURE ARE:
• The hydrogen bonds between C"O and N!H entities lie in
the plane of the sheet. DISULFIDE BOND
• The amino acid R groups are found above and below the • The strongest of the tertiary-structure interactions
plane of the sheet and within a given backbone segment • Result from the 9SH groups of two cysteine residues
alternating between the top and bottom positions. reacting with each other to form a covalent disulfide bond.
UNSRTUCTURED SEGMENTS • Only one of the four tertiary-structure interactions that
• Is a protein secondary structure that is neither an a helix involves a covalent bond.
nor a b pleated sheet • Bond formation may involve
o two cysteine units in the same peptide chain
• This designation is somewhat of a misnomer because all
(intramolecular disulfide bond) or
molecules of a given protein exhibit identical unstructured
o two cysteine units in different chains
segments.
(intermolecular disulfide bond).
ELECTROSTATIC INTERACTION
• Also called salt bridges, always involve the interaction
between an acidic side chain (R group) and a basic side
chain (R group).
• At the appropriate pH, carry charges:
o Acidic side chain being negatively charged
o Basic side chain being positively charged.
o -COOH group becomes a -COO- group and when a -
TERTIARY STRUCTURE OF PROTEINS
NH2 group becomes a -N+H3 group.
• Is the overall three-dimensional shape of a protein that • The interaction that occurs between the two types of side
results from the interactions between amino acid side chains is a positive–negative ion–ion attraction.
chains (R groups) that are widely separated from each
other within a peptide chain. HYDROGEN BONDS
• Can occur between amino acids with polar R groups.
• A variety of polar side chains can be involved, especially
those that possess the following functional groups:
• Hydrogen bonds are relatively weak and are easily

INTERACTION RESPONSIBLE FOR TERTIARY STRUCTURE disrupted by changes in pH and temperature.
• Four types of stabilizing interaction HYDROPHOBIC INTERACTIONS
o Covalent disulfide bonds
• Result when two nonpolar side chains are close to each
o Electrostatic attractions (salt bridges)
other.
o Hydrogen bonds
o Hydrophobic attractions
o Polar R groups pointing outward, toward the aqueous NONCOVALENT INTRACTION
solvent (which is also polar) • Contribute to tertiary structure (electrostatic interactions,
o Nonpolar R groups pointing inward (away from the hydrogen bonds, and hydrophobic interactions) are also
polar water molecules). responsible for the maintenance of quaternary structure.
• London forces • Contribute to quaternary structure are, however, more
o Resulting from the momentary uneven distribution of easily disrupted.
electrons within the side chains
• Common between phenyl rings and alkyl side chains.
• Hydrophobic interactions are weaker than hydrogen
bonds or electrostatic interactions.
• Cumulative effect can be greater in magnitude than the
effects of hydrogen bonding.
SUMMARY OF PROTEIN STRUCTURE
1959
• A protein tertiary structure was determined for the first
time.
• The determination involved myoglobin, a conjugated
protein whose function is oxygen storage in muscle tissue.
• It involves a single peptide chain of 153 amino acids with
numerous a helix segments within the chain.
• The structure also contains a prosthetic heme group, an
iron-containing group with the ability to bind molecular
oxygen. PROTEIN HYDROLYSIS
• When a protein or smaller peptide in a solution of strong
acid or strong base is heated, the peptide bonds of the
amino acid chain are hydrolyzed and free amino acids are
produced.
• The hydrolysis reaction is the reverse of the formation
reaction for a peptide bond. Amine and carboxylic acid
functional groups are regenerated.
• The complete hydrolysis of the tripeptide Ala–Gly–Cys
under acidic conditions produces one unit each of the
amino acids alanine, glycine, and cysteine. The equation
for the hydrolysis is:
QUARTERNARY STRUCTURE OF PROTEINS
• Is the organization among the various peptide chains in a
multimeric protein.
• Only found in multimeric protein
• Have structures involving two or more peptide chains that
PROTEIN DIGESTION
are independent of each other—that is, are not covalently
bonded to each other. • Simply enzyme-catalyzed hydrolysis of ingested protein.
• Most multimeric proteins contain an even number of • The free amino acids produced from this process are
subunits (two subunits 5 a dimer, four subunits 5 a absorbed through the intestinal wall into the bloodstream
tetramer, and so on). and transported to the liver.
• The subunits are held together mainly by hydrophobic • Here they become the raw materials for the synthesis of
interactions between amino acid R groups. new protein.
• Also, the hydrolysis of cellular proteins to amino acids is an
ongoing process, as the body resynthesizes needed
molecules and tissue.
PROTEIN DENATURATION produces coagulation, as in the frying
of an egg
• Is the partial or complete disorganization of a protein’s
characteristic three-dimensional shape as a result of Microwave Disrupts hydrogen bonds by making
disruption of its secondary, tertiary, and quaternary Radiation molecules vibrate too violently;
structural interactions. produces coagulation, as in the frying
of an egg
• The result of denaturation is loss of biochemical activity.
Protein denaturation does not affect the primary structure UV Operates very similarly to the action
of a protein. of heat (e.g., sunburning
Violet Whipping Causes molecules in globular shapes

or Shaking to extend to longer lengths, which
then entangle (e.g., beating egg white
into meringue)
Detergent Affects R-group interactions
Organic Interferes with R-group interactions

Solvents because these solvents also can form
hydrogen bonds; quickly denatures
proteins in bacteria, killing them
(e.g., the disinfectant action of 70%
COOKING
ethanol)
(1) Denatures Proteins – make it easy for enzymes in our body
to hydrolyze/digest protein. Strong Acids Disrupts hydrogen bonds and salt
(2) Kills microorganisms by denaturation of proteins and Bases bridges; prolonged action leads to
(3) Fever (1040 F) – the critical enzymes of the body start actual hydrolysis of peptide bonds
getting denatured. Salts of Heavy Metal ions combine with -SH groups
RENATURATION Metal and form poisonous salts
• Effects of denaturation can be reversed; Reducing Reduces disulfide linkages to produce

• This restoration process, in which the protein is -SH groups
Agents
“refolded,”
• Extensive denaturation changes, the process is usually PROTEIN CLASSIFICATION BASED ON SHAPE
irreversible.
FIBROUS PROTEIN
COAGULATION • Is a protein whose molecules have an elongated shape with
• Loss of water solubility is a frequent physical consequence one dimension much longer than the others.
of protein denaturation • Fibrous proteins tend to have simple, regular, linear
• The precipitation out of biochemical solution of denatured structures.
protein.
GLOBULAR PROTEIN
CAUTERIZATION • Is a protein whose molecules have peptide chains that are
• Heat used to seal small blood vessels folded into spherical or globular shapes.
TEMPERATURE • Water-soluble substances
• A temperature above 1060F (410C) is extremely MEMBRANE PROTEIN
dangerous, as the body’s enzymes begin to be inactivated • Is a protein that is found associated with a membrane
at this level. system of a cell.
• Enzymes, which function as catalysts for almost all body • Structure is somewhat opposite that of globular proteins,
reactions, are protein. with most of the hydrophobic amino acid side chains
• Inactivation of enzymes through denaturation can have oriented outward.
lethal effects on body chemistry
NAME OCCURRENCE AND FUNCTION
ALCOHOL
FIBROUS PROTEINS (INSOLUBLE)
• Important type of denaturing agent.
• Denaturation of bacterial protein takes place when Keratin Wool, feathers, hooves, silk, and
fingernails
isopropyl or ethyl alcohol is used as a disinfectant
• Pure isopropyl or ethyl alcohol is less effective than the Collagens Tendons, bone, and other connective
commonly used 70% alcohol solution. tissue
• Pure alcohol quickly denatures and coagulates the Elastin Blood vessels and ligaments
bacterial surface, thereby forming an effective barrier to Myosin Muscle tissue
further penetration by the alcohol
Fibrin Blood clots
DENATURATING MODE OF ACTION
GLOBULAR PROTEINS (SOLUBLE)
AGENT
Insulin Regulatory hormone for controlling
Heat Disrupts hydrogen bonds by making
molecules vibrate too violently; glucose metabolism
Myoglobin Oxygen storage in muscles COLLAGEN
Hemoglobin Oxygen transport in blood • The most abundant of all proteins in humans (30% of total
body protein), is a major structural material in tendons,
Transferrin Iron transport in blood ligaments, blood vessels, and skin; it is also the organic
Immunoglobulins Immune system responses component of bones and teeth.
• The predominant structural feature within collagen
COMPARISON OF FIBROUS AND GLOBULAR PROTEINS: molecules is a triple helix formed when three chains of
(1) Fibrous proteins are generally water-insoluble, whereas amino acids wrap around each other to give a ropelike
globular proteins dissolve in water. This enables globular arrangement of polypeptide chains.
proteins to travel through the blood and other body fluids
to sites where their activity is needed.
(2) Fibrous proteins usually have a single type of secondary
structure, whereas globular proteins often contain several
types of secondary structure.
(3) Fibrous proteins generally have structural functions that
provide support and external protection, whereas • The rich content of the amino acid proline (up to 20%) in
globular proteins are involved in metabolic chemistry, collagen is one reason why it has a triple-helix
performing functions such as catalysis, transport, and conformation rather than the simpler a helix structure.
regulation. • Proline amino acid residues do not fi t into regular α helices
(4) The number of different kinds of globular protein far because of the cyclic nature of the side chain present and
exceeds the number of different kinds of fibrous protein. its accompanying different “geometry.”
However, because the most abundant proteins in the
human body are fibrous proteins rather than globular
proteins, the total mass of fibrous proteins present exceeds
the total mass of globular proteins present.
The characteristics of two fibrous proteins (a keratin and
collagen) and two globular proteins (hemoglobin and
myoglobin) as representatives of their types are now examined.
\
• Collagen molecules (triple helices) are very long, thin, and
α KERATIN rigid. Many such molecules, lined up alongside each other,
• Is particularly abundant in nature, where it is found in combine to make collagen fibrils.
protective coatings for organisms. • Cross-linking between helices gives the fibrils extra
• It is the major protein constituent of hair, feathers, wool, strength.
fingernails and toenails, claws, scales, horns, turtle shells, • The greater the number of cross links, the more rigid the
quills, and hooves. fibril is.
• The stiffening of skin and other tissues associated with
STRUCTURE OF A TYPICAL α KERATIN
aging is thought to result, at least in part, from an
increasing amount of cross-linking between collagen
molecules.
• The process of tanning, which converts animal hides to
leather, involves increasing the degree of cross-linking.
HEMOGLOBIN
• The globular protein hemoglobin transports oxygen from
the lungs to tissue.
• It is a tetramer (four peptide chains) with each subunit also
containing a heme group, the entity that binds oxygen.
• Microfilaments the “core” unit in the structure of the α • With four heme groups present, a hemoglobin molecule
keratin of hair. These microfilaments in turn coil at even can transport four oxygen molecules at the same time.
higher levels.
• This coiling at higher and higher levels is what produces
the strength associated with a-keratin-containing proteins.
• All levels of coiling organization are stabilized by
attractive forces of the types previously considered in the
discussion of generalized secondary and tertiary protein
structure.
• Particularly important are inter-coil disulfide bridges that
form between cysteine residues.
• Introduction of disulfide bridges within the several levels
• It is the iron atom at the center of the heme molecule that
of coiling structure determines the “hardness” of an α
actually interacts with the O2.
keratin.
• “Hard” keratins, such as those found in horns and nails,
have considerably more disulfide bridges than their softer
counterparts found in hair, wool, and feathers.
MYOGLOBIN MESSENGER PROTEINS
• It functions as an oxygen storage molecule in muscles. • These proteins transmit signals to coordinate biochemical
• Myoglobin is a monomer, whereas hemoglobin is a processes between different cells, tissues, and organs.
tetramer. • A number of hormones that regulate body processes are
• That is, myoglobin consists of a single peptide chain and a messenger proteins, including insulin and glucagon.
heme unit, and hemoglobin has four peptide chains and • Human growth hormone is another example of a
four heme units. messenger protein.
• Thus, only one O2 molecule can be carried by a myoglobin CONTRACTILE PROTEINS
molecule.
• These proteins are necessary for all forms of movement.
• The tertiary structure of the single peptide chain of
• Muscles are composed of filament-like contractile proteins
myoglobin is almost identical to the tertiary structure of
that, in response to nerve stimuli, undergo conformation
each of the subunits of hemoglobin.
changes that involve contraction and extension.
• Myoglobin has a higher affinity for oxygen than does
• Actin and myosin are examples of such proteins.
hemoglobin.
• Human reproduction depends on the movement of sperm.
• Thus, the transfer of oxygen from hemoglobin to
o Sperm can “swim” because of long flagella made up
myoglobin occurs readily.
of contractile proteins.
• Oxygen stored in myoglobin molecules serves as a
reserve oxygen source for working muscles when their STRUCTURAL PROTEINS
demand for oxygen exceeds that which can be supplied by • These proteins confer stiffness and rigidity to otherwise
hemoglobin fluid-like biochemical systems.
CLASSIFICATION BASED ON FUNCTION • Collagen is a component of cartilage, and a Keratin gives
mechanical strength as well as protective covering to hair,
• The functional versatility of proteins stems from:
fingernails, feathers, hooves, and some animal shells.
o Their ability to bind small molecules specifically and
strongly to themselves TRANSMEMBRANE PROTEINS
o Their ability to bind other proteins, often other like • These proteins, which span a cell membrane, help control
proteins, to form fiber-like structures the movement of small molecules and ions through the cell
o Their ability to bind to, and often become integrated membrane.
into, cell membranes. • Many such proteins have channels through which
FOLLOWING LIST INCLUDES SEVERAL MAJOR molecules can enter and exit a cell.
CATEGORIES OF PROTEINS BASED ON FUNCTION: • Such protein channels are very selective, often allowing
CATALYTIC PROTEINS passage of just one type of molecule or ion.
• Proteins are probably best known for their role as STORAGE PROTEINS
catalysts. • These proteins bind (and store) small molecules for future
• Proteins with the role of biochemical catalyst are called use.
enzymes. • During degradation of hemoglobin the iron atoms present
DEFENSE PROTEINS are released and become part of ferritin, an iron-storage
protein, which saves the iron for use in the biosynthesis of
• These proteins, also called immunoglobulins or
new hemoglobin molecules.
antibodies, are central to the functioning of the body’s
• Myoglobin is an oxygen-storage protein present in
immune system.
muscle; the oxygen so stored is a reserve oxygen source
• They bind to foreign substances, such as bacteria and
for working muscle.
viruses, to help combat invasion of the body by foreign
particles. REGULATORY PROTEINS
TRANSPORT PROTEINS • These proteins are often found “embedded” in the exterior
surface of cell membranes.
• These proteins bind to particular small biomolecules and
• They act as sites at which messenger molecules, including
transport them to other locations in the body and then
messenger proteins such as insulin, can bind and thereby
release the small molecules as needed at the destination
initiate the effect that the messenger “carries.”
location.
• Regulatory proteins are often the molecules that bind to
• Bind small biomolecules
enzymes (catalytic proteins), thereby turning them “on”
o Examples are oxygen and other ligands, and
and “off” and thus controlling enzymatic action.
transport them to other locations in the body and
release them on demand. NUTRIENT PROTEINS
• The most well-known example of a transport protein; • These proteins are particularly important in the early
o Hemoglobin, which carries oxygen from the lungs to stages of life, from embryo to infant.
other organs and tissues. • Casein, found in milk, and ovalbumin, found in egg white,
o Transferrin, which carries iron from the liver to the are two examples of such proteins.
bone marrow. o The role of milk in nature is to nourish and provide
o High- and low-density lipoproteins are carriers of immunological protection for mammalian young.
cholesterol in the bloodstream. o Three-fourths of the protein in milk is casein.
• More than 50% of the protein in egg white is ovalbumin.
BUFFER PROTEINS ANTIBODY
• These proteins are part of the system by which the acid- • Is a biochemical molecule that counteracts a specific
base balance within body fluid is maintained. antigen.
• Within the blood, the protein hemoglobin has a buffering
role in addition to being an oxygen carrier.
• Transmembrane proteins regulate the movement of ions in
and out of cells, ensuring that ion concentrations are those
needed for correct acidity/alkalinity.
FLUID-BALANCE PROTEINS
• These proteins help maintain fluid balance between blood
and surrounding tissue.
• Two well-known fluid-balance proteins, found in the
capillary beds of the circulatory system, are albumin and
globulin.
• When increased blood pressure generated by a pumping
heart forces water and nutrients out of the capillaries, these All types of immunoglobulin molecules have much the same
proteins remain behind (since they are too big to cross basic structure:
cellular membranes). (1) Four polypeptide chains are present: two identical heavy
• As their concentration increases (due to less fluid being (H) chains and two identical light (L) chains.
present), osmotic pressure “forces” draw water back into (2) The H chains, which usually contain 400–500 amino acid
the capillaries, which is necessary for fluid balance to be residues, are approximately twice as long as the L chains.
maintained. (3) Both the H and L chains have constant and variable regions.
The constant regions have the same amino acid sequence
GLYCOPROTEINS
from immunoglobulin to immunoglobulin, and the variable
• A protein that contains carbohydrates or carbohydrate regions have a different amino acid sequence in each
derivatives in addition to amino acids immunoglobulin.
COLLAGEN (4) The carbohydrate content of various immunoglobulins
varies from 1% to 12% by mass.
• Qualifies as a glycoprotein because carbohydrate units are
(5) The secondary and tertiary structures are similar for all
present in its structure. This structural feature of collagen,
immunoglobulins. They involve a Y-shaped conformation
not considered previously, involves the presence of the
with disulfide linkages between H and L chains stabilizing
nonstandard amino acids 4-hydroxyproline (5%) and 5-
the structure.
hydroxylysine (1%)
o Derivatives of the standard amino acid proline and ANTIGEN-ANTIBODY COMPLEX
lysine
• The function of the carbohydrate groups in collagen is

related to cross-linking; they direct the assembly of LIPOPROTEINS
collagen triple helices into more complex aggregations • Is a conjugated protein that contains lipids in addition to
called collagen fibrils. amino acids.
IMMUNOGLOBULINS • The major function of such proteins is to help suspend lipids
and transport them through the bloodstream.
• Is a glycoprotein produced by an organism as a protective
• Lipids, in general, are insoluble in blood (an aqueous
response to the invasion of microorganisms or foreign
medium) because of their nonpolar nature.
molecules.
• Different classes of immunoglobulins, identified by PLASMA PROTEIN
differing carbohydrate content and molecular mass, exist. • Is a lipoprotein that is involved in the transport system for
• Serve as antibodies lipids in the bloodstream.
ANTIGEN • These proteins have a spherical structure that involves a
central core of lipid material (triacylglycerols and
• Is a foreign substance, such as a bacterium or virus, that
cholesterol esters) surrounded by a shell (membrane
invades the human body
structure) of phospholipids, cholesterol, and proteins.
PROTEIN METABOLISM
DIGESTION
• Begins in the stomach rather than in the mouth because
saliva contains no enzymes that affect proteins.
• Both protein denaturation and protein hydrolysis occur in
the stomach.
• The partially digested protein (large polypeptides) passes
from the stomach into the small intestine, where digestion
is completed.
THERE IS FOUR MAJOR CLASSES OF PLASMA

LIPOPROTEINS:
Chylomicrons Their function is to transport dietary

triacylglycerols from the intestine to
the liver and to adipose tissue.
Very-Low-Density Their function is to transport

Lipoproteins triacylglycerols synthesized in the
(VLDL) liver to adipose tissue.
Low-Density Their function is to transport

Lipoproteins cholesterol synthesized in the liver
(LDL) to cells throughout the body.
High-Density Their function is to collect excess

Lipoproteins cholesterol from body tissues and
(HDL) transport it back to the liver for
degradation to bile acids.
• The density of a lipoprotein is related to the fractions of

protein and lipid material present.
• The greater the amount of protein in the lipoprotein, the
higher the density.
GASTRIN
• Dietary protein entering the stomach effects the release of
this hormone by stomach mucosa cells.
• Its presence cab cause hydrochloric acid and pepsinogen
secretion.
HCL ACID 3 MAJOR FUNCTION WITHIN THE STOMACH
• Its antiseptic properties kill most bacteria
• Its denaturing action “unwinds” globular proteins, making
peptide bonds more accessible to digestive enzymes.
• its acidity leads to the activation of pepsinogen (inactive
form of Pepsin) because of the hydrochloric acid present,
o Gastric juice has a pH between 1.5 and 2.0
PEPSIN degradation of proteins that were synthesized for other
• Effects the hydrolysis of approximately 10% of peptide functions.
bonds present in proteins, producing a variety of THE AMINO ACIDS FROM THE BODY’S AMINO ACID
polypeptides. POOL ARE USED IN FOUR DIFFERENT WAYS
SECRETIN PROTEIN SYNTHESIS
• neutralization of gastric hydrochloric acid • It is estimated that about 75% of the free amino acids in a
healthy, well-nourished adult go into protein synthesis.
TRYPSIN, CHYMOTRYPSIN, and CARBOXYPEPTIDASE
Proteins are continually needed to replace old tissue
• This basic environment allows for the production of the (protein turnover) and also to build new tissue (growth).
pancreatic digestive enzymes
• Of which attack peptide bonds SYNTHESIS OF NONPROTEIN NITROGEN-CONTAINING
• All examples of proteolytic enzymes COMPOUNDS
• Amino acids are regularly withdrawn from the amino acid
AMINO PEPTIDASE
pool for the synthesis of nonprotein nitrogen-containing
• Secreted by intestinal mucosal cells, also attacks compounds.
peptide bonds. • Such molecules include the purines and pyrimidines of
ZYMOGENS nucleic acids, the heme of hemoglobin, the choline and
• Enzymes of this type are produced in inactive forms ethanolamine of phosphoglycerides, hormones such as
adrenaline, and neurotransmitters such as
• Activated at their site of action
norepinephrine, dopamine, and serotonin.
AMINO ACID UTILIZATION
SYNTHESIS
AMINO ACID POOL
AMINO ACID NUEROTRANSMITTER
• Is the total supply of free amino acids available for use in
the human body Tryptophan Serotonin
DIETARY PROTEINS Norepinephrine

• One of three sources that contributes amino acids to the Tyrosine Dopamine
amino acid pool. Serotonin
• The other two sources are protein turnover and
biosynthesis of amino acids in the liver. SYNTHESIS OF NONESSENTIAL AMINO ACIDS
• When required, the body draws on the amino acid pool for
PROTEIN TURNOVER
raw materials for the production of nonessential amino
• Is the repetitive process in which proteins are degraded acids that are in short supply.
and resynthesized within the human body. • The “roadblock” preventing the synthesis of the essential
• Disease, injury, and “wear and tear” are all causes of amino acids is not lack of nitrogen but lack of a correct
degradation. carbon skeleton upon which enzymes can work.
BIOSYNTHESIS • In general, the essential amino acids contain carbon chains
• By the liver also supplies the amino acid pool with amino or aromatic rings not present in other amino acids or the
acids. However, only the nonessential amino acids can be intermediates of carbohydrate or lipid metabolism.
produced in this manner. NUTRIONOALLY NUTRIONOALLY NONESSENTIAL
NITROGEN BALANCE ESSENTIAL AMINO ESSENTIAL AMINO ACIDS
• is the state that results when the amount of nitrogen taken ACIDS AMINO ACID PRECURSOR
into the human body as protein equals the amount of Alanine Pyruvate
Histidine
nitrogen excreted from the body in waste materials.
Isoleucine Arginine Glutamate
TWO TYPES OF NITROGEN BALANCE
Leucine Asparagine Aspartate
NEGATIVE NOTROGEN BALANCE
• Accompanies a state of “tissue wasting,” because more Lysine Aspartic acid Oxaloacetate
tissue proteins are being catabolized than are being Methionine Cysteine Serine
replaced by protein synthesis.
Phenylalanine Glutamic acid α – ketoglutarate
• Protein-poor diets, starvation, and wasting illnesses
produce a negative nitrogen balance. Threonine Glutamine Glutamate
POSITIVE NITROGEN BALANCE Tryptophan Glycine Serine

• Nitrogen intake exceeds nitrogen output Valine Proline Glutamate
• Indicates that the rate of protein anabolism (synthesis)
Serine 3-
exceeds that of protein catabolism. Phosphoglycerate
No specialized storage forms for amino acids exist in the body, Tyrosine Phenylalanine
as is the case for glucose (glycogen) and fatty acids
(triacylglycerols). Therefore, the body needs a relatively PRODUCTION OF ENERGY
constant source of amino acids to maintain normal metabolism. • Because excess amino acids cannot be stored for later use,
During negative nitrogen balance, the body must resort to the body’s response is to degrade them.
• The degradation process is complex because each of the • The two most encountered keto/amino acid pairs in
20 standard amino acids has a different degradation transamination are a-ketoglutarate/glutamate and
pathway. oxaloacetate/aspartate.
ALL DEGRADATION PATHWAYS
• Amino nitrogen atom is removed and ultimately is
excreted from the body as urea.
• The remaining carbon skeleton is then converted to
pyruvate, acetyl CoA, or a citric acid cycle intermediate,
depending on its makeup, with the resulting energy
production or energy storage.
TRANSAMINATION AND OXIDATIVE
DEAMINATION
TWO STAGE OF AMINO ACIDS DEGREGATION
(1) The removal of the a-amino group and
(2) The degradation of the remaining carbon skeleton.
TWO DIFFERENT TYPES OF BIOCHEMICAL REACTIONS
NEEDED FOR THE REMOVAL OF AMINO GROUPS
(1) Transamination
(2) Oxidative reactions AMINOTRANSFERASE
• Enzyme needed for transamination reaction
TRANSAMINATION REACTIONS
• It effects the e transfer of the amino group from one carbon
• Is a biochemical reaction that involves the interchange of
skeleton to another.
the amino group of an a-amino acid with the keto group of
• There is no loss or gain of amino groups in transamination.
an a-keto acid.
• Amino group transfer is all that occurs.
• Reaction that only involves two amino acids (reactant and
• Requires the presence of pyridoxal phosphate, a
product) and two keto acids (reactant and product).
coenzyme produced from pyridoxine (vitamin B6).
• Two keto/amino acid pairs are involved, with the members
of a pair having a common carbon-chain base.
GLUTAMATE PRODUCTION VIA TRANSAMINATION

• The most important transamination reaction in protein
metabolism, in terms of frequency of occurrence, is the one
in which the keto acid a-ketoglutarate is the amino group
acceptor.
• Glutamate is the amino acid produced when α-
ketoglutarate accepts the amino group.
• The “regenerated” a-ketoglutarate becomes available for
re-participation in the transamination reactions whereby
glutamate was initially produced.
Note also that aspartate is now a carrier of nitrogen atoms that
are to be eliminated from the body as urea.
AMMONIUM ION PRODUCTION VIA OXIDATIVE

DEAMINATION
• Not all glutamates undergo transanimation to produce
aspartate.
• A significant number instead undergo oxidative
deamination
OXIDATIVE DEAMINATION REACTION
• Is a biochemical reaction in which an a-amino acid is
AMINOTRANSFERASE converted into an a-keto acid with release of an ammonium
• Are highly specific relative to which keto acid substrates ion.
they accept. • Occurs primarily in liver and kidney mitochondria.
• Most aminotransferases accept only α-ketoglutarate and to GLUTAMATE DEHYDROGENASE
a lesser extent oxaloacetate.
• Required enzyme for Oxidative deamination of glutamate
• Thus glutamate (from α-ketoglutarate) and aspartate
• Unusual in that it is the only known enzyme that can
(from oxaloacetate) are the two amino acids produced in
function with either NADP+ or NAD+ as a coenzyme.
transamination reactions.
THROUGH TRANSAMINATION INVOLVING α-
KETOGLUTARATE
• The amino groups from many different amino acids are
collected into one type of molecule, the amino acid
glutamate.
GLUTAMATE
• Functions as an amino group donor for further processing
of the amino groups, with the ultimate fate of the amino Note that a-ketoglutarate is a product of this process. It can be
groups being elimination from the body in the form of urea. reused in the first series of transamination reactions.
• The “nitrogen removal problem” has been reduced from
The NADH and H1 formed can participate in the electron
dealing with twenty amino acids to dealing with one amino
transport chain and oxidative phosphorylation to produce ATP
acid.
molecules.
TWO PATHWAYS FOR FURTHER PROCESSING OF
• The net equation for combined action of an
GLUTAMATE MOLECULES
Aminotransferase (transamination) and Glutamate
(1) A second transamination reaction that produces the amino Dehydrogenase (oxidative deamination):
acid aspartate
(2) Production of ammonium ion (NH4 +) via oxidative
deamination. • The NH4+ so produced, a toxic substance if left to
ASPARTATE PRODUCTION VIA TRANSAMINATION accumulate in the body, is then converted to urea in the
urea cycle.
• Transamination in which glutamate is the reacting amino
acid and oxaloacetate is the reacting keto acid produces SERINE AND THREONINE
aspartate as the new amino acid. • Exhibit different behavior from the other amino acids.
Note that the second product in this reaction is a-ketoglutarate. • They undergo direct deamination by a dehydration–
hydration process rather than oxidative deamination.
• This different behavior results from the presence of a side-
chain β-hydroxyl group, a feature unique to these two
acids.
• The direct deamination reaction for serine is:
THE UREA CYCLE

• Is a cyclic biochemical pathway in which urea is produced,
for excretion, using ammonium ions and aspartate
molecules as nitrogen sources.
• The only means the body has of removing ammonia; failure Cats Citrulline Awesome Aspartate
of any part of this cycle leads to an accumulation of
Always Argininosuccin Umbrellas Urea
ammonia with severe retardation or death.
ate
• Produced in the liver and is transported in the blood to the
kidneys and eliminated from the body in urine. Ask Arginine Orange Ornithine
• In the pure state, urea is a white solid with a melting point
of 1338C.
NITROGEN STANDPOINT
• Net effect of transamination and deamination reactions is
production of ammonium ions and aspartate molecules.
• Both are processed further in the urea cycle.
AMMONIUM IONS
• Enter the cycle indirectly, being first incorporated into
another molecule (carbamoyl phosphate) that then enters
the cycle’s first step.
ASPARTATE MOLECULES
• Enter the cycle directly in the cycle’s second step.
UREA
• Is very soluble in water (1 g per 1 mL), is odorless and
colorless, and has a salty taste. (Urea does not contribute
to the odor or color of urine.) STEPS OF UREA CYCLE
• With normal metabolism, an adult excretes about 30 g of • Note that the urea cycle occurs partially in the
urea daily in urine, although the exact amount varies with mitochondria and partially in the cytosol and that ornithine
the protein content of the diet. and citrulline must be transported across the inner
THREE AMINO ACIDS IN THE UREA CYCLE mitochondrial membrane.
• Arginine, Ornithine, and Citrulline, the latter two of STEP 1: CARBAMOYL GROUP TRANSFER
which are nonstandard amino acids—that is, amino acids
• The carbamoyl group of carbamoyl phosphate is
not found in protein.
transferred to ornithine to form citrulline
• Structurally, all three of these amino acids have the same
• Ornithine transcarbamoylase
carbon chain.
STEP 2: CITRULLINE-ASPARTATE CONDENSATION

• Citrulline is transported into the cytosol where a
condensation reaction between it and aspartate occurs.
CARBAMOYL PHOSPHATE • Produces argininosuccinate, is catalyzed by
argininosuccinate synthase
• The “fuel” for the urea cycle.
• This fuel is formed from ammonium ion (from oxidative
deamination), carbon dioxide (from the citric acid cycle),
water, and two ATP molecules.
• The formation equation for carbamoyl phosphate is:
Colored Carbonyl For Fumarate • Citrulline reacts with aspartate to produce

phosphate argininosuccinate utilizing ATP.
• Recall that the original source of both nitrogen is UREA CYCLE NET REACTION
glutamate, the collecting agent for amino acid nitrogen • The equivalent of a total of four ATP molecules is expended
atoms. in the production of one urea molecule.
• The flow of the nitrogen can be shown by these reactions: • Two ATP molecules are consumed in the production of
carbamoyl phosphate, and the equivalent of two ATP
molecules is consumed in Step 2 of the urea cycle,
o Where an ATP is hydrolyzed to AMP and PPi and the
PPi is then further hydrolyzed to two Pi.
STEP 3: ARGININOSUCCINATE CLEAVAGE UREA

• The enzyme argininosuccinate lyase catalyzes the • Are formed via the urea cycle is excreted in urine. Urea is
cleavage of argininosuccinate into arginine, a standard one of several molecules eliminated from the body through
amino acid, and fumarate, a citric acid cycle intermediate. urine.
LINKAGE BETWEEN THE UREA AND CITRIC ACID CYCLES
• The net equation for urea formation shows fumarate, a citric
acid cycle intermediate, as a product.
• This fumarate enters the citric acid cycle, where it is
converted to malate and then to oxaloacetate, which can
then be converted to aspartate through transamination.
• The aspartate then re-enters the urea cycle at Step 2
• Besides undergoing transamination, the oxaloacetate
produced from fumarate of the urea cycle can be
(1) converted to glucose via gluconeogenesis
(2) condensed with acetyl CoA to form citrate or
STEP 4: UREA FROM ARGININE HYDROLYSIS (3) converted to pyruvate.
• Hydrolysis of arginine produces urea and regenerates
ornithine, one of the cycle’s starting materials.
• Arginase
• The oxygen atom present in the urea comes from the water
involved in the hydrolysis.
UREA CYCLE INTERMEDIATES AND NO PRODUCTION
• The ornithine is transported back into the mitrochondria,
where it becomes available to participate in the urea cycle MID-1980s
again. • Arginine and Citrulline, are involved in an important
biochemical reaction that is completely independent of the
urea cycle.
• This newly discovered biochemical role is participation in
the production of the biochemical messenger molecule
nitric oxide, NO.
AMINO ACID CARBON SKELETON
• The removal of the amino group of an amino acid by
transamination/oxidative deamination produces an α-keto
acid that contains the carbon skeleton from the amino acid.
• Each amino acid has a different degradation pathway for
its carbon skeleton.
• alanine and serine, the degradation requires a single step.
• The 20 degradation pathways do not produce 20 different
products.
7 DEGRADATION PRODUCTS • The nonessential amino acids can be made in 1–3 steps.
FOUR DEGRADATION PRODUCTS The essential ones have biosynthetic pathways that
require 7–10 steps.
• Are citric acid cycle intermediates: a-ketoglutarate,
• Most bacteria and plants can synthesize all the amino acids
succinyl CoA, fumarate, and oxaloacetate.
by pathways not present in humans.
THREE DEGRADATION PRODUCTS
GLYCOLYSIS AND CITRIC ACID CYCLE INTERMEDIATES
• Are pyruvate, acetyl CoA, and acetoacetyl CoA.
• Are the starting materials for the biosynthesis of the 11
nonessential amino acids.
• Glycolysis intermediates 3-phosphoglycerate and
pyruvate.
• Citric acid cycle intermediates oxaloacetate and α-
ketoglutarate.
ALANINE, ASPARTATE, AND GLUTAMATE (NONESSENTIAL)
• Are biosynthesized by transamination of the appropriate a-
keto acid starting material.
GLUCOGENIC AMINO ACIDS

• Is an amino acid that has a carbon-containing degradation TYROSINE
product that can be used to produce glucose via
• Is a nonessential amino acid obtained from the essential
gluconeogenesis.
amino acid phenylalanine in a one-step oxidation that
• Amino acids that are degraded to citric acid cycle involves molecular O2, NADPH, and the enzyme
intermediates can serve as glucose precursors. phenylalanine hydroxylase.
KETOGENIC AMINO ACID o Lack of this enzyme causes the metabolic disease
• is an amino acid that has a carbon-containing degradation phenylketonuria (PKU).
product that can be used to produce ketone bodies HEMOGLOBIN CATABOLISM
• Amino acids that are degraded to acetyl CoA or
acetoacetyl CoA can contribute to the formation of fatty
RED BLOOD CELLS (RBC)
acids or ketone bodies • Primary function is to deliver oxygen to, and remove
carbon dioxide from, body tissues.
ADD ONS
• Mature red blood cells have no nucleus or DNA. Instead,
• Even though acetyl CoA can enter the citric acid cycle,
they are filled with the red pigment hemoglobin.
there can be no net production of glucose from it.
• Acetyl groups are C2 species, and such species only RBC FORMATION
maintain the carbon count in the cycle because two CO2 • Occurs in the bone marrow, and about 200 billion new red
molecules exit the cycle. blood cells are formed daily.
• Thus, amino acids that are degraded to acetyl CoA (or • The life span of a red blood cell is about four months.
acetoacetyl CoA) are not glucogenic. • RBC oxygen-carrying ability is due to the protein
• Amino acids that are degraded to pyruvate can be either hemoglobin present in such cells
glucogenic or ketogenic. HEMOGLOBIN
• Pyruvate can be metabolized to either oxaloacetate
• Is a conjugated protein
(glucogenic) or acetyl CoA (ketogenic).
• The protein portion is called globin, and the prosthetic
• Only two amino acids are purely ketogenic: leucine and
group (nonprotein portion) is heme.
lysine.
• Heme contains four pyrrole groups joined together with an
• Nine amino acids are both glucogenic and ketogenic:
iron atom in the center
those degraded to pyruvate, as well as tyrosine,
phenylalanine, and isoleucine (which have two
degradation products).
• The remaining nine amino acids are purely glucogenic.
AMINO ACID BIOSYNTHESIS
• The classifi cation of amino acids as essential or
nonessential for humans roughly parallels the number of
steps in their biosynthetic pathways and the energy
required for their synthesis.
• It is the iron atom in heme that interacts with O2, forming a
reversible complex with it.
• This complexation increases the amount of O2 that the
blood can carry by a factor of 80 over that which simply
“dissolves” in the blood.
OLD RBC
• Are broken down in the spleen (primary site) and liver
(secondary site).
• Part of this process is degradation of hemoglobin.
• Structure employs a notation, common in heme chemistry,
DEGRADATION OF HEMOGLOBIN
in which letters are used to denote attachments to the
GLOBIN PROTEIN pyrrole rings; such notation easily distinguishes the
• Is hydrolyzed to amino acids, which become part of the attachments.
amino acid pool. • The structure’s linear arrangement of pyrrole rings also
saves space compared to the heme-like representation of
Fe ATOMS
the rings.
• Becomes part of ferritin • However, the linear structure incorrectly implies that the
• An iron storage protein arrangement of the pyrrole rings that results from the ring
• Saves the iron for use in biosynthesis of new hemoglobin opening is linear (straight-line); rather, the pyrrole rings
molecules actually have a hemi-like arrangement.
HEME (TETRAPYRROLE) 2ND STEP OF HEME DEGRADATION
• Is degraded to bile pigments and eliminated in feces or • Biliverdin is converted to bilirubin.
urine • This change involves reduction of the central methylene
• Degradation of heme begins with a ring-opening reaction bridge of biliverdin.
in which a single carbon atom is removed.
• The product is called biliverdin.
• Usually occurs in the spleen.

• The bilirubin is then transported by serum albumin to the
liver, where it is rendered more water-soluble by the
attachment of sugar residues to its propionate side chains
(P side chains).
• The solubilizing sugar is glucuronate (glucose with a
−COO- group on C-6 instead of a -CH2OH group).
IMPORTANT CHARACTERISTICS OF THE REACTION
(1) Molecular oxygen, O2, is required as a reactant.
(2) Ring opening releases the iron atom to be incorporated
into ferritin.
(3) The product containing the excised carbon atom is carbon
monoxide
CARBON MONOXIDE
• Reacts with functioning hemoglobin, forming a CO–
• The solubilized bilirubin is excreted from the liver in bile,
hemoglobin complex; this decreases the oxygen-carrying
which flows into the small intestine.
ability of the blood.
• Here the bilirubin diglucuronide is changed, in a multistep
• CO–hemoglobin complexes are very stable; CO release to
process, to either stercobilin for excretion in feces or
the lungs is a slow process.
urobilin for excretion in urine.
BILIVERDIN • Both stercobilin and urobilin still have tetrapyrrole
• Alternative rendering structure of biliverdin is: structures.
• Intestinal bacteria are primarily responsible for the
changes that produce stercobilin and urobilin.
INTERRELATIONSHIPS AMONG METABOLIC
PATHWAYS
• The metabolic pathways of carbohydrates, lipids, and
proteins are integrally linked to one another.
o A change in one pathway can affect many other
pathways.
FEASTING (OVEREATING)
• Ingestion of food in excess of energy needs causes the
body to store a limited amount as glycogen and the rest as
fat.
BILE PIGMENT
• The tetrapyrrole degradation products obtained from
heme.
• is a colored tetrapyrrole degradation product present in
bile.
• Normally, the body excretes 1–2 mg of bile pigments in
urine daily and 250–350 mg of bile pigments in feces daily.
BILIVERDIN AND BILIRUBIN
• Respectively, green and reddish-orange in color.
FASTING (NO FOOD INGESTION)
• When no food is ingested, the body uses its stored
STERCOBILIN glycogen and fat for energy
• Has a brownish hue and is the compound that gives feces
their characteristic color.
UROBILIN
• Is the pigment that gives urine its characteristic yellow
color.
JAUNDICE STARVATION (CONTINUED FASTING BEYOND GLYCOGEN
• Results in higher than normal bilirubin levels in the blood DEPLETION)
and gives the skin and white of the eye yellow tint. • When glycogen stores are depleted, body protein is
• Can occur as a result of liver diseases, such as infectious broken down to amino acids, which are used to synthesize
hepatitis and cirrhosis, that decrease the liver’s ability to glucose.
process bilirubin. • The glucose serves as an energy source for the brain and
nervous system.
LOCAL COLORATION
• Also, in the liver, fats are converted to ketone bodies,
• Deep bruise is also related to the pigmentation associated which are another energy source for the brain.
with heme, biliverdin, and bilirubin.
• The changing color of the bruise as it heals reflects the
dominant degradation product present as the tissue
repairs itself.
INTERRELATIONSHIPS AMONG CARBOHYDRATE, LIPID,
AND PROTEIN METABOLISM
B VITAMINS AND PROTEIN METABOLISM

• Transamination reactions are dependent on the cofactor
PLP, which involves vitamin B6.
• Oxidation deamination requires use of NAD+, which
involves niacin, as an oxidizing agent.
• All eight B vitamins—including vitamin B12, the least used
B vitamin in terms of cofactor function—are needed as
cofactors at least once in obtaining these degradation
products.
• Vitamin B12 is needed in the formation of the degradation
pro duct succinyl CoA.

BIOCHEM-TRANS With Additional Protein Topic

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

BIOCHEM-TRANS With Additional Protein Topic

Uploaded by

Copyright:

Available Formats

PHARM 13: PHARMACEUTICALS IN BIOCHEMISTRY

CARBOHYDRATES • Nucleolus – site of ribosome assembly

• Plants have two main uses for the carbohydrates they

STEREOISOMERISM: ENANTIOMERS AND

The conventions that connect these model specifications with a

MOST OTHER DIASTEREOMERS (TWO OR MORE CHIRAL

FUNCTIONAL GROUP ISOMERS DEXTROROTATORY AND LEVOROTATORY COMPOUNDS

A major difference between glyceraldehyde and

SPECIAL TERMINOLOGY FOR CYCLIC MONOSACCHARIDE

• Is a rearrangement of the projection formula for D-glucose ANOMERS

• Monosaccharide oxidation can yield three different types

STRONG OXIDIZING AGENTS

PHOSPHATE ESTER FORMATION

• These phosphate esters of glucose are stable in aqueous

• The remainder of this section deals with the specifi c

• he glycosidic linkage between the two glucose units is

• Cellobiose is a reducing sugar, has three isomeric forms in

MALTOSE AND CELLOBIOSE

Note that all three of the oligosaccharide markers have a

The absence or presence of a fifth monosaccharide (attached to

Storage Polysaccharides Starch and glycogen

Structural cellulose and chitin

• Amylose molecules tend to have spiral-like structures,

• There are approximately 50,000 disaccharide units per

• Major breakdown products AEROBIC PATHWAYS

• The net result of this change is that carbon 1 of glucose is

STEP 6: OXIDATION AND PHOSPHORYLATION USING Pi

STEP 10: PHOSPHORYLATION OF ADP

Remember that two ATP molecules are produced for each

Conversion to Formation requires aerobic (oxygen-

Conversion to Formation occurs under anaerobic

Conversion to Limited to some microorganisms.

• A key concept in considering these fates of pyruvate is the

• It is significant that each of the three pathways for

• An overall reaction for the production of ethanol from

• Lactate buildup contributes to muscle soreness, muscle

• The net equation for conversion of pyruvate to lactate is

• Adding the two equation; one glucose produces two

Reverse process of the 1st step of glycogenesis

• The newly formed pyruvate is then converted via

• There are two other locations where gluconeogenesis and

• The glycogen degradation pathways have names ending

Note the production of two NADPH molecules per glucose 6-

PENTOSE PHOSPHATE PATHWAY

• Major function is that of the coenzymes in metabolic CASEIN

AMINO ACID SIDE CHAIN

POLAR BASIC AMINO ACIDS

• 19 of 20 amino acids have chiral center

NAME ISOELECTRIC NAME ISOELECTRIC

Alanine 6.01 Leucine 5.98

• The covalent disulfide bond of cystine is readily broken,

• The reaction between a carboxylic acid and an amine to

• Have pain-reducing effects; short term pain relief

SECONDARY STRUCTURE OF PROTEINS

FURTHER FEATURES OF THE B PLEATED SHEET

• Hydrogen bonds are relatively weak and are easily

SUMMARY OF PROTEIN STRUCTURE

Violet Whipping Causes molecules in globular shapes

Detergent Affects R-group interactions

Organic Interferes with R-group interactions

• Effects of denaturation can be reversed; Reducing Reduces disulfide linkages to produce

• The function of the carbohydrate groups in collagen is