AMINO ACIDS, PEPTIDES AND

PROTEINS

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 Objectives
• Identify the general structure of amino acids
• Classify 20 naturally occurring amino acids in to groups
• Discuss the property of 20 naturally occurring amino
acids
• Discuss force involved in binding amino acids to form
polypeptides and proteins
• List the functions of Protein in living system
• Classify proteins based on different criteria's
• Discuss the levels of protein structures
• Discuss the techniques employed to study protein
 What are amino acids?

 Amino acids are the basic structural units of proteins consisting of

 A basic amino group (-NH2)
 An acidic carboxyl group ( -COOH)
 A hydrogen atom (-H)
 A distinctive side chain (-R)
 Each amino acid has a central carbon, called the α-carbon, to
which the four different groups are attached
 One of the 20 amino acids, proline, is not an α-amino acid but an α-
imino acid

The general formula

for the naturally
occurring amino acids
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 cont…
 At physiologic pH (approximately pH 7.4), the carboxyl
group is dissociated, forming the negatively charged
carboxylate ion (–COO–), and the amino group is
protonated (–NH3+) called zwitterion (dipolar)
 In proteins, almost all of these carboxyl and amino groups
are combined through peptide linkage.
 Only L-Amino Acids Occur in Proteins
 With the sole exception of glycine, the α-carbon of amino
acids is chiral.

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 Classification of amino acids
• Amino acids are classified according to the properties of
their (–R) side chains as; polar, non-polar, acidic and
basic
1. Amino acids with non-polar side chains
• Each of these amino acids has a non-polar side chain that
does not gain or lose protons or participate in hydrogen or
ionic bonds
• Within proteins, the side chains of these amino acids tend
to cluster together.
• This clustering through hydrophobic interactions stabilize
protein structure
• Tryptophan and tyrosine, and to a much lesser extent
phenylalanine, absorb ultraviolet light at 280 nm.
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NONPOLAR SIDE CHAINS

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• Amino acids with uncharged polar side
chains:
 The R groups of these amino acids are more
soluble in water, because of the functional
groups that can form hydrogen bonds with
water.

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cont
3. Amino acids with Positively Charged (Basic) R Groups:
• The side chains of the basic amino acids accept protons.
• At physiologic pH the side chains of lysine and arginine
are fully ionized and positively charged.
• Histidine is weakly basic, and the free amino acid is
largely uncharged at physiologic pH

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Cont…
4. Amino acids with negatively charged (acidic) R Groups
• The amino acids aspartic and glutamic acid are proton
donors.
• At physiologic pH, the side chains of these amino acids
are fully ionized, containing a negatively charged
carboxylate group (–COO–).
• They are, therefore, called aspartate or glutamate to
emphasize that these amino acids are negatively charged
at physiologic pH

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Biological or Physiological Classification
This classification is based on the source of amino acids for the
organism.
1. Essential Amino Acids
• Amino acids which are not synthesized in the body are called
essential amino acids.
• The essential amino acids are *Arginine , *Histidine, isoleucine,
leucine, lysine, methionine, phenylalanine, threonine,
tryptophan, and valine.
2. Non- Essential Amino Acids
• These amino acids can be biosynthesized in adequate amounts
within the organism.
• Non- Essential Amino Acids are Alanine , Asparagine, Aspartic
Acid, Cysteine, Glutamic Acid, Glutamine, Glycine, Proline,
Serine, Tyrosine
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 Cont…
Semi-essential amino acids

• Two amino acids are grouped under semi-essential

amino acids since they can be synthesized within the
organism but their synthesis is not sufficient amounts.
• In that they should also be provided in the diet.
• Semi-essential amino acids include Arginine and
Histidine.

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 Classification Based on the Fate of Each Amino acid in
Mammal
• Amino acids can be classified as Glucogenic, ketogenic
and both glucogenic and ketogenic.
 Glucogenic Amino Acids
• Those amino acids in which their carbon skeleton gets
degraded to pyruvate, α ketoglutarate, succinyl CoA,
Fumarate and oxaloacetate and then converted to Glucose
and Glycogen, are called as Glucogenic amino acids.
• These include:- Alanine, Cysteine, glycine, Arginine,
glutamine, Isoleucine, tyrosine.

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 Ketogenic Amino Acids
• Those amino acids in which their carbon skeleton is
degraded to Acetoacetyl CoA, or acetyl CoA then
converted to acetone and β-hydroxy butyrate which are
the main ketone bodies are called ketogenic amino acids.
• Leucine and lysine are the only exclusively ketogenic
amino acids found in proteins.

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 Cont…

 Ketogenic and glucogenic Amino Acids

• The division between ketogenic and glucogenic amino

acids is not sharp for amino acids (Tryptophan,
phenylalanine, tyrosine and Isoleucine are both ketogenic
and glucogenic).

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 Peptides
• Proteins are macromolecules formed by polymerization of
amino acids in a polyamide structure.
• These amide bonds in proteins, is known as peptide
bonds.
• Formed by linkage of α-carboxyl group of one amino acid
with α-amino groups of the next amino acid.

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 Cont…

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 Cont…

Characteristics of the peptide bond:

• The peptide bond has a partial double-bond character

• Is rigid and planar
• Generally a trans bond

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 Cont…

 The –C=O and –NH groups of the peptide bond are

uncharged, and neither accept nor release protons
over the pH range of 2–12.
 The – C=O and – NH groups of the peptide bond
are polar, and are involved in hydrogen bonds,
for example, in α-helices and β-sheet structures
• The charged groups present in polypeptides
 the N-terminal (α-amino) group,

 the C-terminal (α-carboxyl) group, and
 any ionized groups present in the side chains of
the constituent amino acids.
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 Cont…

• PROTEINS
• The word protein is derived from Greek word,
proteious meaning the first, the most important or
the most eminent.
• So, proteins are the major components of any living
organism.
• Proteins are natural substances with high molecular
weights ranging from 5,000 to many millions.

• Besides Carbon, Hydrogen and Oxygen, they also

contain Nitrogen, and sometimes, Sulfur and
Phosphorous.
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 Cont…

 The most important biological molecules:

 in building up and maintenances of the structure of the
body
 source of energy in the course of metabolism in the body.
 Proteins are the molecular instruments in which genetic
information is expressed.
• Proteins are macromolecules with a backbone formed by
polymerization of amino acids in a polyamide structure.
• Gene Regulation
• Signal Transduction
• Catalytic activity
• Defense ex. Antibodies(immunoglobuliins)
• Blood clotting factors
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Membrane transport 22
 Cont…
• Classification of proteins
• Even though there is no universally accepted
classification system, proteins may be classified
on the basis of their
 Composition
 Solubility
 Shape
 Biological function and
 On their three dimensional structure.

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 Cont…
1. Composition:-
A. Simple protein:
only contained amino acids residues .
B. Conjugated Proteins:
• Yields amino acids and other organic and
inorganic components
E.g.
 Lipoprotein
 Phosphoprotein
 Metalloprotein
 Glycoprotein
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 Cont…

2. Solubility
i) Albumins and histones: These proteins such as
egg albumin and serum albumin are readily
soluble in water and coagulated by heat.
ii) Globulins: these proteins are present in serum,
muscle and other tissues and are soluble in dilute
salt solution but sparingly in water.

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 3. Shape
A. Fibrous proteins
• In these protein, the molecule are constituted by several
coiled cross-linked polypeptide
1. Collagens: the major protein of the connective tissue,
insoluble in water, acids or alkalis. But they are convertible
to water-soluble gelatin, easily digestible by enzymes.
2. Elastins: present in tendons, arteries and other elastic
tissues, not convertible to gelatin.
3. Keratins: protein of hair, nails etc.
B. Globular proteins: These are globular or ovoid in shape,
soluble in water and constitute the enzymes, oxygen
carrying proteins, hormones etc.
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 4. On their Biological Functions
• Proteins are sometimes described as the "workhorses" of the
cell because they do So many things Like:
• Enzymes:- kinases, transaminases etc.
• Storage proteins:- myoglobin, ferretin
• Regulatory proteins:- peptide hormones, DNA binding
proteins
• Structural protein:- collagen, proteoglycan
• Protective proteins:- blood clotting factors,
Immunoglobins,
• Transport protein:- Hemoglobin, plasma lipoproteins
• Contractile or motile Proteins:- Actin, tubulins

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 5. On their level of organization
• Primary, secondary, tertiary and quaternary
A) Primary Structure of Proteins
• The primary structure of a protein is defined by the linear
sequences of amino acid residues.
• Protein contain between 50 and 2000 amino acid residues.
• The mean molecular mass of an amino acid residue is about
110 Dalton units (Da).
• The amino acid composition of a peptide chain has a profound
effect on its physical and chemical properties of proteins.
• Protein rich in polar amino acids are more water soluble.
• Proteins rich in aliphatic or aromatic amino groups are
relatively insoluble in water and more soluble in cell
membranes.
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 Cont…

B) Secondary Structure
• The secondary structure of a protein refers to the local
structure of a polypeptide chain, which is determined by
Hydrogen bond.
• The Interactions are between the carbonyl oxygen group
and the amide hydrogen of near by peptide bond.
• There are two types of secondary structure
• the ∝-helix and
• the β- pleated sheet

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 Cont…

 α-Helix
• The α-helix is a rod like structure with peptide chains
tightly coiled
• The side chains of the component amino acids extend
outward from the central axis.
• Each amide carbonyl group is hydrogen bonded to the
amide hydrogen of a peptide bond that is 4 - residues away
along the same chain.
• There are 3.6 amino acids residues per turn of the helix
• A very diverse group of proteins contains α-helices. For
example, keratin, myoglobin etc

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 Cont…

• The α-helix is disrupted by proline residues, because its

secondary amino group is not geometrically compatible
with the right-handed spiral of the α-helix.
• Large numbers of charged amino acids (like, glutamate,
aspartate, histidine, lysine, or arginine) also disrupt the helix
by forming ionic bonds, or by electrostatically repelling
each other
• Amino acids with bulky side chains, such as tryptophan, or
branched chain amino acids, such as valine or isoleucine,
can interfere with formation of the α-helix if they are
present in large numbers.

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Fig. α-Helix showing
peptide backbone

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  β-Sheet
• β-Sheet structures are made from highly extended
polypeptide chains that link together by hydrogen bonds
between the neighboring strands
• the backbone of the polypeptide chain is extended into a
zigzag rather than helical structure.
• The zigzag polypeptide chains can be arranged side by side
to form a structure resembling a series of pleats.
• In this arrangement, called a sheet, hydrogen bonds are
formed between adjacent segments of polypeptide chain.

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 Cont…

• The adjacent polypeptide chains in a sheet can be

either parallel or anti-parallel.

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• Unlike the α-helix, β-sheets are composed of two or more
peptide chains
• In β-sheets the hydrogen bonds formed are interchain and
perpendicular to the polypeptide backbone.

C. Tertiary structure
 is formed by combinations of secondary structural
elements into a three-dimensional organization.
 it is mainly stabilized by non-covalent interactions,
such as hydrogen bonds, hydrophobic bond,
electrostatic bond and covalent disulfide bond.

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 Cont…

1. Protein folding is the complex process by which tertiary

structures form within the cell.
2. Regions of proteins that are capable of folding
independently and that often have distinct functions are
called domains.
3. The side chains of highly polar amino acids tend to reside
on the exterior of proteins, where they can form hydrogen
bonds with water.
4. The side chains of nonpolar amino acids are normally
clustered in the interior of proteins to shield them from
water.

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 D. Quaternary structure

• Quaternary structure refers to a complex or an assembly

of two or more separate peptide chains.
1. In most cases, as in hemoglobin, the subunits are held
together by non-covalent interactions.
2. In some multi subunit proteins, such as immunoglobulins,
the subunits are held together by disulfide bonds or other
covalent interactions
• If the subunits are identical, it is a homogeneous
quaternary structure; but if there are dissimilarities, it is
heterogeneous.

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 e.g. Hemoglobin

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 Cont…
e.g. Hemoglobin has 4 chains, two of them are α and
two are β.
• Aspartate transcarbamoylase –has 12 polypeptide
sub units
• Poliovirus protein coat –contains 60 polypeptides
• Tobacco mosaic virus protein- has 2120 subunits
held together non covalently
• polymers may be dimers, trimmers, tetramers and
so on.

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 Denaturation of proteins
• Proteins have finite lifetimes.
• They are also subject to environmental damages like
oxidation proteolysis, denaturation and other irreversible
modifications.
• Denaturation involves the destruction of the higher level
structural organization (20, 30 and 40) of protein with the
retention of the primary structure by denaturing agents.
• A denatured protein loses its native physico-chemical and
biological properties.
• The denatured protein may retain its biological activity by
refolding (renaturing) when the denaturing agent is
removed.
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 Cont…

Denaturing agents
1. Physical factors
• Temperature, pressure, mechanical shear force, ultrasonic
vibration and ionizing radiation causes the protein to lose its
biological activity.
2. Chemical factors
• Acids and alkalis, organic solvents (acetone, ethanol),
detergents (cleaning agents), certain amides urea, alkaloids,
and heavy metal salts (Hg, Zn, Pb, Cd…) Cause the
denaturation.

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 Cont…
• Properties of a Denatured Proteins
A. an increase in number of reactive and functional group in
the composition of the native protein molecule ( side chain
group of amino acids, COOH, NH2, SH, OH … etc)
B. Reduced solubility and pronounced tendency for
precipitation due to loss of the hydration shell
C. Configurational alteration of the protein molecule
D. Loss of biological activity evoked by the disarrangement of
the native structural molecular organization.
E. Access of proteolytic enzymes in comparison with the
native protein

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