PROTEINS

Characteristics of Proteins Conjugated (complex) proteins:

 A protein is a naturally-occurring, unbranched A protein that has one or more non-amino acid entities
polymer in which the monomer units are amino (prosthetic groups) present in its structure: Prosthetic group
acids may be organic or inorganic
 Proteins are most abundant molecules in the cells
after water – account for about 15% of a cell’s
overall mass
 Elemental composition - Contain Carbon (C),
Hydrogen (H), Nitrogen (N), Oxygen (O), and Sulfur
(S)
 The average nitrogen content of proteins is 15.4% by
mass
 Also present are Iron (Fe), phosphorus (P) and some
other metals in some specialized proteins
 General definition: A protein is a naturally-occurring,
unbranched polymer in which the monomer units
Protein Classification Based on Shape Fibrous
are amino acids. Proteins:
 Specific definition: A protein is a peptide in which at
least 40 amino acid residues are present: Alpha-Keratin & Collagen
 The terms polypeptide and protein are often used
interchangeably to describe a protein • The polypeptide chains are arranged in long strands
 Several proteins with >10,000 amino acid residues or sheets
are known
 Common proteins contain 400–500 amino acid • Have long, rod-shaped or string-like molecules that
residues can intertwine with one another and form strong
 Small proteins contain 40–100 amino acid residues fibers; water-insoluble
 More than one polypeptide chain may be present in
a protein: • Structural functions
 Monomeric : Contains one polypeptide chain
 Multimeric: Contains 2 or polypeptide chains Globular Proteins: Myoglobin & Hemoglobin

• The polypeptide chains are folded into spherical or

Protein Classification Based on Chemical
globular shapes
Composition
• Nonpolar amino acids are in the interior, polar
Simple proteins: amino acids are on the
• A protein in which only amino acid residues are
present: surface
– More than one protein subunit may be present but
all subunits contain only amino acids • Water-soluble which allows them to travel through
the blood and other body fluids to sites where their
Albuminoids - keratin in skin, hair, nails; collagen in
activity is
cartilage
needed
Albumins- egg albumin, serum albumin
Globulins- antibodies
• Dynamic
Histones- chromatin in chromosomes
functions
 other locations in the body and release them on
demand.

• Messenger proteins: transmit signals to coordinate

biochemical

processes between different cells, tissues, and organs.

– Insulin and glucagon - regulate carbohydrate

metabolism

– Human growth hormone – regulate body

growth

• Contractile proteins: Necessary for all forms of

movement.
Protein Classification Based on Function
– Muscles contain filament-like contractile
• Proteins play crucial roles in most biochemical proteins (actin and myosin).
processes.
– Human reproduction depends on the
• The diversity of functions exhibited by proteins far movement of sperm – possible because of
exceeds the role of other biochemical molecules contractile proteins.

• The functional versatility of proteins stems from: • Structural proteins: Confer stiffness and rigidity

– Ability to bind small molecules specifically – Collagen is a component of cartilage

and strongly
– Keratin gives mechanical strength as well as
– Ability to bind other proteins and form fiber- protective covering to hair, fingernails,
like feathers, hooves, etc.

structures, and • Transmembrane proteins: Span a cell membrane

and help control
– Ability integrated into cell membranes
the movement of small molecules and ions.

– Have channels – help molecules to enter and

Major Categories of Proteins Based on Function exist the cell.

• Catalytic proteins: Enzymes are best known for their – Transport is very selective - allow passage of
catalytic role. one type of

– Almost every chemical reaction in the body molecule or ion.

is driven by an enzyme
• Storage proteins: Bind (and store) small molecules.
• Defense proteins: Immunoglobulins or antibodies
are central to functioning of the body’s immune – Ferritin - an iron-storage protein - saves iron
system. for use in the biosynthesis of new
hemoglobin molecules.
• Transport proteins: Bind small biomolecules, e.g.,
oxygen and other ligands, and transport them to
 – Myoglobin - an oxygen-storage protein
present in muscle
• Regulatory proteins: Often found “embedded” in the
exterior surface of cell membranes - act as sites for
receptor molecules
– Often the molecules that bind to enzymes
(catalytic proteins), thereby turning them
“on” and “off,” and thus controlling
enzymatic action.
• Nutrient proteins: Particularly important in the early
stages of life -
from embryo to infant.
– Casein (milk) and ovalalbumin (egg white)
are nutrient proteins
– Milk also provide immunological protection
for mammalian
young.
Amino Acids: The Building Blocks for
Proteins
• Amino acid - An organic compound that contains
both an amino (-NH2) and a carboxyl (-COOH) group
attached to same carbon atom
– The position of carbon atom is Alpha (a)
– -NH2 group is attached at alpha (a) carbon
atom.
– -COOH group is attached at alpha (a) carbon
atom.
– R = side chain –vary in size, shape, charge,
acidity, functional groups present,
hydrogen-bonding ability, and chemical
reactivity.
– >700 amino acids are known
– Based on common “R” groups, there are 20
standard amino acids
Nomenclature
• Common names assigned to the amino acids are
currently used.
• Three letter abbreviations - widely used for naming:
– First letter of amino acid name is compulsory
and capitalized followed by next two letters
not capitalized except in the case of
Asparagine (Asn), Glutamine (Gln) and
tryptophan (Trp).
• One-letter symbols - commonly used for comparing
amino acid
sequences of proteins:
– Usually the first letter of the name
– When more than one amino acid has the
same letter the most
abundant amino acid gets the 1st letter.
• All amino acids differ from one another by their R-
groups
– There are 20 common (standard) amino
acids
• Standard amino acids are divided into four groups
based on the properties of R-groups
• Non-polar amino acids: R-groups are non-polar
– Such amino acids are hydrophobic-water
fearing (insoluble in water)
– 8 of the 20 standard amino acids are non
polar
 – When present in proteins, they are located Polar Neutral Amino Acids
in the

interior of protein where there is no polarity

Non-Polar Amino Acids

Polar Acidic and Basic Amino Acids

• Polar amino acids: R-groups are polar

– Three types: Polar neutral; Polar acidic; and

Polar basic

• Polar-neutral: contains polar but neutral side chains

– Seven amino acids belong to this category

• Polar acidic: Contain carboxyl group as part of the

side Essential Amino Acids
chains
• Essential Amino acid: A standard amino acid needed
– Two amino acids belong to this category for protein synthesis that must be obtained from
dietary sources – adequate amounts cannot be
• Polar basic: Contain amino group as part of the side synthesized in human body.
chain
• Nine of the 20 standard amino acids are considered
– Two amino acids belong to this category essential

Essential
Amino Acids

Arginine* Methionine
Histidine Phenylalanine
Isoleucine Threonine
Leucine Tryptophan
Lysine Valine
*Required for growth in children and is not essential for • The length of the amino acid chain can vary from a
adults. few amino acids to hundreds of amino acids.

Some of the first informations on the biological value of
dietary proteins came from studies on rats. In one series of
experiments, young rats were fed diets containing 18%
protein in the form of either casein (a milk protein), gliadin
(a wheat protein), or zein (a corn protein)
• Such a chain of covalently-linked amino acids is
called a peptide.
• The covalent bonds between amino acids in a
peptide are called peptide bonds (amide).

Results:

Casein: rats remained healthy and grow normally

Gliadin: rats maintained their weight but did not

grow much

Zein: rats not only failed to grow but began to lose

weight, & eventually died if kept on this diet

Nature of Peptide Bond

• by convention, the structure of peptides is

Since casein evidently supplies all the required amino acids
in the correct proportions needed for growth, it is called a
complete protein.
A complete protein contains all the essential amino acids in
the proper amounts. An incomplete protein is low in one or
more of the essential amino acids, usually lysine,
tryptophan, or methionine. Except for gelatin, proteins from
animal sources are complete, whereas proteins from
vegetable sources are incomplete except soy protein.
represented beginning with the amino acid whose
amino group is free (N-terminal end). The other end
contains a free carboxyl group and is the C-terminal
end
amino acids are added to a to a peptide by forming peptide
bonds with the C-terminal amino acid

Complementary proteins are incomplete proteins which

when served together,

complement each other and provide all the essential amino

acids

PEPTIDES
Nature of Peptide Bond

• Under proper conditions, amino acids can bond

together to produce an unbranched chain of amino
acids.

– The reactions is between amino group of one amino

acid and carboxyl group of another amino acid.
Biochemically Important Small Peptides
Many relatively small peptides are biochemically active: • Aspartame (Asp-Phe) - dipeptide sold under trade
names Equal and Nutrasweet; ~180x as sweet as
-Hormones sucrose
– Neurotransmitters

- Antioxidants
- - Artificial sweeteners

• Small Peptide Hormones:

– Best-known peptide hormones: oxytocin
and vasopressin
– Produced by the pituitary gland
– Nonapeptide (nine amino acid residues)
with six of the residues held in the form
of a loop by a disulfide bond formed
between two cysteine residues

•
Small Peptide Antioxidants
Glutathione (Glu–Cys–Gly) – a tripeptide – is
Primary Structure of Proteins
present is in high levels in
most cells Four Types of Structures
• Regulator of oxidation–reduction reactions.
• Glutathione is an antioxidant and protects
cellular contents from oxidizing agents such as
– Primary Structure
peroxides and superoxides
– Highly reactive forms of oxygen often – Secondary Structure
generated within the cell in response to bacterial
invasion
• Unusual structural feature – Glu is bonded to – Tertiary Structure
Cys through the side-chain carboxyl group.
– Quaternary
• Primary Structure is the order in
which amino acids are linked
together in a protein by peptide
bonds;
• the backbone of the protein
molecule
Small Peptide Artificial Sweeteners
 • Every protein has its own
unique amino acid sequence
– Frederick Sanger (1953)
sequenced and determined the
primary structure for the first
protein - Insulin
T Georgetown anemia: …..Val-His-Leu-
he order in which the amino acid
residues of a peptide molecule are
linked is the amino acid sequence of
the molecule; differences in the
chemical and physiologic properties
of peptides result from differences
in the amino acid sequence.
e.g., a) Bradykinin vs Boguskininin
Bradykinin
- partly responsible for triggering
pain, welt formation (as in
scratches), movement of smooth
muscle, and lowering of blood
pressure.
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
Boguskinin:
completely inactive, hence, the
name bogus or false
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe
b) Normal Hb:…..Val-His-Leu-Thr-
Pro-Glu-Glu-Lys-Ser-Ala-…..
Sickle-cell Hb: …..Val-His-Leu-Thr-
Pro-Val-Glu-Lys-Ser-Ala-…..
Thr-Pro-Glu-Lys-Lys-Ser-Ala-…..
 only two possible
arrangements for the peptide
backbone for the following
reasons:
– For two amino acids linked
through a peptide bond six
atoms lie in the same
plane
– The planar peptide linkage
structure has considerable
rigidity, therefore rotation
of groups about the C–N
bond is hindered
Secondary Structure of Proteins – Cis–trans isomerism is
• Arrangement of atoms of possible about C–N bond.
peptide backbone in space. – The trans isomer is the
preferred orientation
The only bond responsible for the 2o
structure of proteins is H-bonding
between peptide bonds, the – C = O
• of one peptide group and the – N –
H of another peptide linkage
farther along the backbone.

The peptide linkages are

essentially planar thus allows
The two most common types :
alpha-helix (a-helix) and the beta-
pleated sheet (b-pleated sheet).

Alpha-helix (α-helix)

• A single protein chain adopts a shape that

resembles a coiled spring (helix):

– H-bonding between amino acids with in the

same chain –intramolecular H- bonding

– Coiled helical spring

– R-groups stay outside of the helix -- not

enough room for them to stay inside

– The helix is so tightly wound that the space

in the center is too small for solvent
molecules to enter
 • Completely extended protein chain segments in
same or different molecules

• H-bonding between different chains –

intermolecular H- bonding

a) parallel – chains run in the same direction

b) antiparallel – chains run in opposite

direction;

Beta-Pleated Sheets more stable because of fully collinear H- bonds

• Completely extended protein chain segments in

same or different molecules governed by
intermolecular or intramolecular H-bonding

• H-bonding between different parts of a single chain

– intramolecular H-bonding

• Side chains below or above the axis

“U-turn” structure – most frequently encountered

Tertiary Structure of Proteins

• The overall three-dimensional shape of a
protein

• Results from the interactions between amino

acid side chains (R groups) that are widely
separated from each other.

• Defines the biological function of proteins

 • Proteins may have, in general, either of the two
forms of tertiary structures: (a) fibrous and
(b) globular

fibrous proteins (insoluble): mechanical strength,

structural components, movement

globular proteins (soluble): transport, regulatory,

enzymes

• In general 4 types of interactions are observed.

– Disulfide bonding

– Electrostatic interactions

– H-Bonding

Hydrophobic interactions

Four Types of Interactions

• Disulfide bond: covalent, strong, between two

cysteine groups; the strongest of the 3o bonds

• Link chains together and cause chains to twist

and bend

Four Types of Interactions

1. Electrostatic interactions (ionic interaction,

salt linkages): Salt Bridge between charged
side chains of acidic and basic amino acids
– -OH, -NH2, -COOH, -
CONH2

2. H-Bonding between polar, acidic and/or 3. Hydrophobic interactions: Between non-

basic R groups polar side chains
– For H-bonding to occur, the H must be attached
to O, N or F

4. Drill
 • Present only in proteins that have 2 or more
polypeptide chains (subunits)

• Subunits are generally independent of each

other - not covalently bonded

• Proteins with quaternary structure are often

referred to as oligomeric proteins

• Contain even number of subunits

Quaternary Structure of Proteins

• Quaternary structure of protein refers to the

organization among the various polypeptide chains
in a multimeric protein:

• Highest level of protein organization

Quaternary Structure of Proteins
 • Organic component of bones and teeth

• Predominant structure - triple helix

• Rich in proline (up to 20%) – important to maintain

structure

Globular Proteins: Myoglobin

Fibrous Proteins: Alpha-Keratin • Globular Proteins: Myoglobin:

• Provide protective coating for organs – An oxygen storage molecule in muscles.

• Major protein constituent of hair, – Monomer - single peptide chain with one
heme unit
feather, nails, horns and turtle shells
– Binds one O2 molecule
• Mainly made of hydrophobic amino acid
– Has a higher affinity for oxygen than
residues
hemoglobin.
• Hardness of keratin depends upon -S-S- – Oxygen stored in myoglobin molecules
bonds serves as a reserve oxygen source for
working muscles
– More –S-S– bonds make nail and bones
• An oxygen carrier molecule in blood
hard and hair brittle
• Transports oxygen from lungs to tissues

• Tetramer (four polypeptide chains) - each subunit

has a heme group

• Can transport up to 4 oxygen molecules at time

• Iron atom in heme interacts with oxygen

Fibrous Proteins: Collagen

• Most abundant proteins in humans (30% of total

body protein)

• Major structural material in tendons, ligaments,

blood vessels, and skin
Glycoproteins
• Conjugated proteins with carbohydrates linked
to them:

– Many of plasma membrane proteins are

glycoproteins

– Blood group markers of the ABO system

are also glycoproteins

– Collagen and immunoglobulins are

glycoproteins

• Collagen -- glycoprotein

– Most abundant protein in human

body (30% of total body protein)

– Triple helix structure

– Rich in 4-hydroxyproline (5%) and 5-

hydroxylysine (1%) — derivatives

– Some hydroxylysines are linked to Lipoproteins

glucose, galactose, and their
disaccharides – help in aggregation of • Lipoprotein: a conjugated protein that contains
collagen fibrils. lipids in addition to

Immunoglobulins amino acids

• Glycoproteins produced as a protective • Major function - help suspend lipids and

response to the invasion of microorganisms or
foreign molecules - antibodies against antigens.
• Immunoglobulin bonding to an antigen via
variable region of an immunoglobulin occurs
through hydrophobic interactions, dipole –
dipole interactions, and hydrogen bonds.
• Carbohydrate molecules attached to the heavy
chains aid in
determining the destinations of immunoglobulins in the
tissues
transport them through the bloodstream
• Four major classes of plasma lipoproteins:
– Chylomicrons: Transport dietary
triacylglycerols from intestine
to liver and to adipose tissue.
– Very-low-density lipoproteins (VLDL):
Transport triacylglycerols synthesized in
the liver to adipose tissue.
– Low-density lipoproteins (LDL):
Transport cholesterol synthesized in the
liver to cells throughout the body.
 – High-density lipoproteins (HDL): Collect
excess cholesterol from body tissues
and transport it back to the liver for
degradation to bile acids.

Protein Denaturation
• Partial or complete disorganization of protein’s
tertiary structure

• Cooking food denatures the protein but does

not change protein nutritional value

• Coagulation: Precipitation (denaturation of

proteins)

– Egg white - a concentrated solution of

protein albumin - forms a jelly when
heated because the albumin is
denatured

• Cooking:

– Denatures proteins – Makes it easy for

enzymes in our body to hydrolyze/digest
protein

– Kills microorganisms by denaturation of

proteins

– Fever: >104ºF – the critical enzymes of

the body start getting denatured