Amino Acids, Peptides And

Proteins

By
Dr. Gul Muhammad (PhD Scholar)
Chairman Pharmaceutical
Chemistry
University Of Balochistan, Quetta
 Amino Acids
Definition: Amino acids are a group of organic compounds containing two
functional groups (amino and carboxyl).
• The amino group ( -NH2) is basic while the carboxyl group ( -COOH ) is
acidic in nature.
• There are about 300 amino acids occur in nature. Only 22 of them occur
in proteins.
Structure: Each amino acid has 4 different groups attached to α- carbon
( which is C-atom next to COOH). These 4 groups are : amino group,
COOH, Hydrogen atom and side Chain (R).
 Classification of amino acids
Amino acid classification based on the structure
The 20 standard amino acids found in protein
structure are divided into seven distinct groups.
1.Aliphatic amino acids:
2.Hydroxyl group containing amino acids:
3.Sulfur containing amino acids:
4.Acidic amino acids and their amides:
5.Basic amino acids:
6.Aromatic amino acids:
7.Imino acids:
 1. Aliphatic amino acids
These are monoamino monocarboxylic
acids. This group consists of most simple
amino acids.

A) Glycine - Gly - G
B) Alanine - Ala - A
C) Valine - Val - V
D) Leucine - Leu - L
E) Isoleucine - Ile - I
 Glycine, Alanine, Valine
A. Glycine: Small, simple amino acid. R –
group is hydrogen.
• It is a non essential amino acid.
• Glycine is allosteric inhibitor of
glutathione synthetase.

B. Alanine: It is a non essential amino acid.

Alanine is allosteric inhibitor of
glutathione synthetase.
• D-Alanine: is a component of bacterial
cell wall.
• Β-Alanine is found in pantothenic acid.

C. Valine: It is essential amino acid.

• It has an aliphatic hydrophobic
isopropyl ( 3Carbon ) side chain.
 Leucine, Isoleucine
D. Leucine: It is an essential amino acid.
• It has an aliphatic hydrophobic isopropyl
( 4Carbon ) side chain.

E. Isoleucine: It is an essential amino acid.

• It has an aliphatic hydrophobic isopropyl
(4Carbon) side chain like leucine but not
identical.
2. Hydroxyl group containing amino acids (-OH)

A. Serine - Ser - S
B. Threonine - Thr - T
C. Tyrosine - Tyr - Y
 Serine, Threonine, Tyrosine
A. Serine: It is a non essential amino acid.
• It has a alcohol group, is a site for
phosphorylation of many proteins.

B. Threonine: It is a essential amino acid.

• Threonine alcohol side group is a target
for phosphorylation of proteins.

C. Tyrosine: It is a non essential amino

acid.
• The hydroxyl group of tyrosine imparts
slight polarity to the side chain and is a
site for phosphorylation in proteins.
Sulfur containing amino acids (Cysteine , Methionine)
A. Cysteine:: It is a non essential amino acid.
• Cystine, another important sulfur
containing amino acid, is formed by the
condensation of two molecules of
cysteine.

B. Methionine: It is an essential amino acid.

• In genetic code methionine is coded by
codon AUG. This codon is called start
codon. Methionine is first amino acid used
to build a protein chain.
Acidic amino acids and their amides

A. Aspartic acid - Asp - D

B. Asparagine - Asn - N
C. Glutamic acid - Glu - E
D. Glutamine - Gln - Q
 Aspartic Acid, Asparagine, Glutamic Acid And Glutamine

A. Aspartic Acid: It is a non essential amino acid.

• Aspartic is capable of forming ionic bonds and
involved in chemical reactions.

B. Asparagine: It is non essential amino acid. And

Basic in nature having 2 amino groups.

C. Glutamic Acid: It is a non essential amino acid.

• Vitamin K2 carboxylates glutamate residues in
certain proteins to give carboxy glutamate. This
modification allows protein to bind calcium an
essential event in blood clotting cascade.

D. Glutamine: It is a non essential amino acid.

• It is very important compound in
transamination reactions.
 5.Basic amino acids (Lysine, Arginine, Histidine)
A. Lysine: It is an essential amino acid.
These are strongly polar.

B. Arginine: It is a semi essential amino

acid.
• It contain guanidino group and is
monocarboxylic acid.
• It is an intermediate in urea cycle and
is precursor for nitric oxide.

C. Histidine: • It is an semi essential amino

acid.
• It contains imidazole ring.
6. Aromatic amino acids (Phenyl Alanine, Tryptophan)
A. Phenyl Alanine: It is an
essential amino acid.
• It contains benzene ring.

• B. Tryptophan: • It is a essential
amino acid.
• It contains indole ring.

Note: Tyrosine also come in

aromatic amino acid also but we
discussed it in (Hydroxyl group
containing amino acids).
 7.Imino acids (Proline)
• Proline containing pyrrolidine ring is a
unique amino acid.
• It has an imino group ( =NH ). Threrefore,
proline is an α- imino acid.
Classification of amino acids based on polarity:
• Amino acids are classified into 4 groups based on their polarity.
1. Non – polar amino acids:
• These amino acids are also referred to as hydrophobic.
• They have no change on R-group.
e.g. glycine, alanine, leucine, isoleucine, valine, methionine,
phenyl alanine, tryptophan and proline.
2. Polar amino acids with no charge on R group:
• These amino acids, as such, carry no charge on the Rgroup.
• They however possess groups such as hydroxyl, sulfhydryl and amide and
participate in hydrogen bonding of protein structure.
e.g., glycine, serine, threonine, cysteine, glutamine, asparagine and tyrosine.
3. Polar amino acids with positive R- group:
• They are polar having electron deficit Alkyl (R) group. e.g., lysine, arginine,
histidine.
4. Polar amino acids with negative R- group:
• The dicarboxylic mono amino acids – aspartic acid and glutamic acid are
considered in this group.
 Nutritional classification of amino acids
A) Essential or indispensable amino acids:
• The amino acids which cannot be synthesized by the body
and need to be supplied through the diet are called
essential amino acids.
• They are required for proper growth and maintenance of
the individual.
e.g., Arginine, Histidine (Semi essential), Valine, Isoleucine,
Leucine, Lysine, Methionine, Phenyl alanine, Threonine,
Tryptophan (PTV TIM HALL).
B) Non – essential amino acids:
• The body can synthesize about 10 amino acids to meet
the biological needs, hence they need not be consumed in
the diet.
• These are glycine, alanine, serine, cysteine, aspartate,
asparagine, glutamate, glutamine, tyrosine and proline.
 Based on their metabolic fate
• The carbon skeleton of amino acids can serve as a
precursor for the synthesis of glucose ( glucogenic) or fat
( ketogenic ) or both From metabolic veiw point, amino
acids are divided into three groups.
1. Glucogenic amino acids: These amino acids can serve as
precursor for the formation of glucose or glycogen. e.g.
alanine, aspartate, glycine, methionine etc.
2. Ketogenic amino acids: Fat can be synthesized from
these amino acids. Two amino acids leucine and lysine are
ketogenic.
3.Glucogenic and ketogenic Amino acids: The four amino
acids (Phenyl alanine, Isoleucine, Tryptophan, Tyrosine).
They are precursors for the synthesis of glucose as well as
fat.
 New amino acids
In addition to 20 L – amino acids that take part in protein
synthesis, recently two more new amino acids are described.
They are Selenocysteine – 21st amino acid, Pyrrolysine – 22
nd amino acid.
1. Selenocysteine: They occurs at the active site of several
enzymes.
e.g., Thioredoxin reductase, Glutathione peroxidase, De –
iodinase, Glycine reductase.
Selenoprotein P, a glycoprotein containing 10 selenocysteine
residues, found in mammalian blood. It has an antioxidant
function and its concentration falls in selenium deficiency.
• The stop codon UGA can code for Selenocysteine
• Selenocysteine is enzymatically generated from serine
directly on the t RNA and then incorporated into proteins.
2. Pyrrolysine: The STOP codon UAG can code for pyrrolysine.
 Acid-Base Properties
• Zwitter ion is a hybrid molecule containing positive
and negative ionic groups.
• The amino acids rarely exist in a neutral form with
free carboxylic and free amino groups.
• In strongly acidic pH, the amino acid is positively
charged ( cation ).
• In strongly alkaline pH, the amino acid is negatively
charged ( anion ).
• Each amino acid has a characteristic pH at which it
carries both positive and negative charges and
exists as zwitter ion.
• Isoelectric pH is defined as the pH at which a
molecule exists as a zwitter ion or dipolar ion and
carries no net charge.
Functions & Significance
Functions & Significance
 Peptides
• 20 amino acids are commonly found in protein.
• These 20 amino acids are linked together through “peptide bond forming
peptides and proteins.
• The chains containing less than 50 amino acids are called “peptides”, while
those containing greater than 50 amino acids are called proteins”.
• α-carboxyl group of one amino acid (with side chain R1) forms a covalent
peptide bond with α-amino group of another amino acid (with the side chain
R2) by removal of a molecule of water.
• The result is : Dipeptide (i.e. Two amino acids linked by one peptide bond).
• The dipeptide can then forms a second peptide bond with a third amino acid
(with side chain R3) to give Tripeptide.
• Repetition of this process generates a polypeptide or protein of specific
amino acid sequence.
• Each polypeptide chain starts on the left side by free amino group of the first
amino acid enter in chain formation.
• It is termed (N- terminus).
• Each polypeptide chain ends on the right side by free COOH group of the
last amino acid and termed (Cterminus).
 Peptide bond
• The amino acids are held together in a protein by
covalent peptide bonds or linkage cementing material
between amino acids
• When amino group of an amino acid combines with the
carboxyl group of another amino acid, a peptide bond is
formed
• Peptides containing more than 10 amino acids are
referred as polypeptide.
 Functions of peptide bond
• It usually found in trans configuration.
• The peptide bond is a partial double bond.
• N- partially positive, O- partially negative.
• Shorthand to read peptides:
• The amino acids in a peptide or protein are
represented by the 3-letter or one letter
abbreviation.
• This is the chemical shorthand to write
peptide.
 Naming of peptides
• The amino acid suffixes –ine (glycine), -an
(tryptophan), -ate (glutamate) are changed to –yl
with the exception of C-terminal amino acid.
• E.g, Glutamyl-cysteinyl-glycine

• +H3N –glutamate - cysteine - glycine - COO- Amino acids in a

peptide.
• E -C -G = One letter
symbols
• Glu - Cys - Gly = Three letter
symbols
• Glutamyl - cysteinyl - glycine = Peptide name
 Types of Peptides
1. Dipeptide: Two amino acids joined by one peptide bond.
• E.g. Aspartame which acts as sweetening agent being
used in replacement of cane sugar. It is composed of
aspartic acid and phenyl alanine.
2. Tripeptides: 3 amino acids linked by two peptide bonds.
• E.g. GSH which is formed from 3 amino acids (glutamic
acid, cysteine and glycine).
• It helps in absorption of amino acids, protects against
hemolysis of RBC by breaking H2O2 which causes cell
damage.
3. Polypeptides: 10- 50 amino acids.
• E.g. Insulin, a polypeptide hormone. Insulin is consists of
51 amino acids with 2 chains.
 Proteins
• Proteins are the most abundant organic molecules of the
living system.
• They occur in the every part of the cell and constitute about
50% of the cellular dry weight.
• Proteins form the fundamental basis of structure and
function of life.
• The proteins are nitrogenous macromolecules composed of
many amino acids.
• The term protein is derived from a Greek word proteios,
meaning first place.
• Berzelius ( Swedish chemist ) suggested the name proteins
to the group of organic compounds that are utmost
important to life.
• In 1839 Dutch chemist G.J.Mulder while investing the
substances such as those found in milk, egg, found that they
could be coagulated on heating and were nitrogenous
compounds.
 Biomedical importance of proteins
1. Proteins are the main structural components of the cytoskeleton. They are
the sole source to replace nitrogen of the body.
2. Bio chemical catalysts known as enzymes are proteins.
3. Proteins known as immunoglobulins serve as the first line of defense
against bacterial and viral infections.
4. Several hormones are protein in nature.
5. Structural proteins like actin and myosin are contractile proteins and help
in the movement of muscle fibre.
6. Some proteins present in cell membrane, cytoplasm and nucleus of the cell
act as receptors.
7. The transport proteins carry out the function of transporting specific
substances either across the membrane or in the body fluids.
8. Storage proteins bind with specific substances and store them, e.g. iron is
stored as ferritin.
9. Few proteins are constituents of respiratory pigments and occur in
electron transport chain, e.g. Cytochromes, hemoglobin, myoglobin.
10. Under certain conditions proteins can be catabolized to supply energy.
11. Proteins by means of exerting osmotic pressure help in maintenance of
electrolyte and water balance in the body.
 Structure of proteins
• Proteins have different level of
organization;
• Primary structure: The linear
sequence of amino acid forming the
backbone of proteins.
• Secondary structure: The spatial
arrangement of protein by twisting of
the polypeptide chain.
• Tertiary structure: The three
dimensional structure of a functional
protein.
• Quaternary structure: Some of the
proteins are composed of two or more
polypeptide chains referred to as
subunits. The spatial arrangement of
these subunits is known as quaternary
structure.
 Primary structure
• The linear sequence of amino
acids held together by peptide
bonds in its peptide chain.
• The peptide bonds form the back
bone.
• The free –NH2 group of the
terminal amino acid is called as N-
terminal end and the free –COOH
end is called C-terminal end.
• It is a tradition to number the
amino acids from Nterminal end as
No.1 towards the C-terminal end.
• Presence of specific amino acids
at a specific number is very
significant for a particular function
of a protein.
 Secondary structure
• The spatial arrangement of protein by twisting of the polypeptide
chain.
• The amino acids are located close to each other in their sequence.
• Two chief types of secondary structures, α-Helix and β-sheet.
α-Helix: α-Helix is the most common spiral structure of protein.
• α-Helical structure was proposed by Pauling and Coreyin 1965.
• The salient feature: The α-Helix is a tightly packed coiled structure
with amino acid side chains extending outward from the central axis.
• The α-Helix is stabilized by extensive hydrogen bonding formed
between H atom attached to peptide N, and O atom attached to
peptide C.
• The H-bonds are individually weak but collectively, strong enough to
stabilize the helix.
• All the peptide bonds, except the first and last in polypeptide chain,
participate in hydrogen bonding.
• Each turn of helix contains 3.6 amino acids and travels a distance of
0.54 nm.
 The salient feature (Remaining)
• The spacing of each amino acid is 0.15 nm.
• α-Helix is a stable conformation formed spontaneously with the
lowest energy.
• The right handed α-Helix is more stable than the left handed helix
• Certain amino acids (particularly proline) disrupt the α-Helix.
• Large number of acidic and basic amino acids are also interfere with
α-Helix structure.
 Secondary structure
• β-pleated sheet: An another form of secondary structure in which
two or more polypeptides (or segments of the same peptide chain) are
linked together by hydrogen bond between H- of NH- of one chain and
carbonyl oxygen of adjacent chain (or segment).
• β-Pleated sheet may be formed either by separate polypeptide chains
(H-bonds are inter chain) or a single polypeptide chain folding back on
to itself (H-bonds are intrachain)
 Secondary structure (β-pleated sheet)

• Parallel and anti-

parallel β- sheets.
• The polypeptide chains
in the β-sheets may be
arranged either in
parallel or anti-parallel
direction.
Secondary structure (Triple helix & Reverse Turns or β-bends)

Triple helix : Collagen is rich in proline and hydroxy proline

and cannot form a α-helix or β-Pleated sheet.
• Collagen forms a triple helix.
• The triple helix is stabilized by both non covalent as well
as covalent bonds.

Reverse Turns or β-bends : Since the polypeptide chain

of a globular protein changes direction two or more times
when it folds, the conformation known as Reverse turns
or β-bends. Reverse turns usually occur on the surfaces
of globular proteins.
 Super secondary structures (Motifs)
• Varies combinations of
secondary structure, called
super secondary structure, are
commonly found in globular
proteins. These are;
1. β- α- β unit: The β- α- β unit
consists of two parallel β-
pleated sheets connected by an
intervening strand of α –helix.
2. Greek key: A conformation that
takes its name from a design
often found on classical Greek
pottery.
Super secondary structures (Motifs)
3. β-meander: The β-meander
consists of five β-Pleated sheets
connected by reverse turns. The
β-meander contains nearly as
many hydrogen bonds as an α-
helix and its common occurrence
probably reflects the stability
conferred by this extensive
hydrogen bonding.
4. β- barrel: A beta barrel is a beta-
sheet composed of tandem
repeats that twists and coils to
form a closed toroidal structure in
which the first strand is bonded to
the last strand (hydrogen
bond). Beta-strands in many beta-
barrels are arranged in an
antiparallel fashion.
 Tertiary structure
• The three dimensional structure of a protein.
• It is a compact structure with hydrophobic side chains held interior while
the hydrophilic groups are on the surface of the protein.
• This type of arrangement ensures stability of the molecule.
Domains: Used to represent the basic unit of protein structure (tertiary)
and function. A polypeptide with 200 amino acids normally consists of
two or more domains.
Bonds of Tertiary structure:
1. The hydrogen bonds,
2. Disulfide bonds(-S-S )
3. Ionic interactions (electrostatic bonds) and
4. Hydrophobic interactions also contribute to the tertiary structure of
proteins.
 Quaternary structure
• Majority of the proteins are composed of single polypeptide
chains.
• Some of the proteins, consists of two or more polypeptides
which may be identical or unrelated.
• Such proteins are termed as oligomers and possess
quaternary structure.
• The individual polypeptide chains are known as monomers,
protomers or subunits.
• A dimer consists of two polypeptides while a tetramer has
four.
• Importance of oligomeric proteins: These proteins play a
significant role in the regulation of metabolism and cellular
function. e.g. hemoglobin, LDH.
 Classification of proteins
• Three major types of classifying proteins based on their function,
chemical nature and solubility and nutritional importance.
1. Functional classification of proteins
2. Chemical nature and solubility
3. Nutritional importance

1. Functional classification of proteins

Structural proteins: Keratin of hair and nails, collage of bone

• Contractile proteins: myosin, actin
• Enzymes or catalytic proteins: Hexokinase, pepsin
• Transport proteins: Hemoglobin, serum albumin
• Regulating proteins: Insulin, growth hormone
 Simple proteins (Globular proteins)
• These are spherical or oval in shape, soluble in water or other
solvents and digestible.
1. Albumins: They are soluble in water and coagulated by heat.
e.g serum albumin, ovalbumin (egg), lactalbumin (milk)
2. Globulins: These are insoluble in pure water, but soluble in
dilute salt solutions and coagulated by heat. They are
precipitated by half saturation with ammonium sulphate or by
full saturation with sodium chloride.
e.g., serum globulins, egg globulins.
3. Glutelins: These are plant proteins, insoluble in water or
neutral salt solutions, soluble in dilute acids or alkalies. They
are rich in glutamic acid. They are large molecules and can be
coagulated by heat.
e.g., glutelin (wheat), oryzenin (rice).
Simple proteins (Globular proteins)
4. Prolamines: They are soluble in 70-80% alcohol, but
insoluble in pure water. They are rich in proline but lack
in lysine.
E.g., gliadin (wheat), zein (maize).
5. Histones: These are basic proteins, rich in arginine and
histidine, with alkaline isoelectric pH. They are soluble in
water, dilute acids and salt solutions but insoluble in
ammonia. They form conjugated proteins with nucleic
acids (DNA) and porphyrins.
e.g., nucleohistones, chromosomal nucleoproteins.
6. Protamines: These are soluble in water, dilute acids and
alkalies. They are not coagulated by heating. They
contain large number of arginine and lysine residues,
and are strongly basic. These are also found in
association with nucleic acids.
 Simple proteins (Fibrous proteins)
• These are fibrous proteins with great stability and very
low solubility and form supporting structures of animals.
1. Collagens: are connective tissue proteins lacking
tryptophan
2. Elastins: these proteins are found in elastic tissues such
as tendons and arteries
3. Keratins: these are present in exoskeletal structures e.g.
hair, nails, horns. Human hair has a higher content of
cysteine.
 Conjugated proteins
• They are combinations of proteins with a non-protein part, called
prothetic group. These are
1. Glycoproteins: Glycoproteins are the proteins with carbohydrate moiety
as the prosthetic group. The term mucoprotein is used if the
carbohydrate content is more than 4%. Blood group antigens and many
serum proteins are glycoproteins.
2. Lipoproteins: These are the proteins loosely combined with lipid
components. They occur in blood and on cell membranes Serum
lipoproteins, membrane lipoproteins.
3. Nucleoproteins: These are the proteins attached to nucleic acids, e.g.
Histones. The DNA carries negative charges, which combines with
positively charged proteins.
4. Phosphoproteins: These contain phosphorous. E.g. casein and vitellin
of egg yolk. The phosphoric acid is esterified to the hydroxyl groups of
serine and threonine residues of proteins.
5. Metalloproteins: They contain metal ion as their prothetic group. Several
enzymes contain metallic elements such as Fe, Co, Mn, Zn, Cu, Mg,
etc. E.g., Ferritin (Fe), Carbonic anhydrase (Zn), Ceruloplasmin (Cu).
 Conjugated proteins
• 6. Chromoproteins: These are the proteins with colored
prosthetic groups.
a) Hemoproteins: All hemoproteins are Chromoproteins
which carry heme as the prosthetic group.
b) Hemoglobin: Respiratory protein found in RBCs.
c) Cytochromes: These are the mitochondrial enzymes of the
respiratory chain.
d) Catalase: This enzyme decomposes H2O2 to water and
O2.
e) Flavoproteins: Is a cellular oxidation-reduction protein
which has riboflavin a constituent of B-complex vitamin as
its prosthetic group. This is yellow in color.
f) Visual purple: Is a protein of retina in which the prosthetic
group is a corotenoid pigment which is purple in colour.
 Derived proteins (Primary)
a) Proteans: These are earliest products of protein
hydrolysis by enzymes, dilute acids, alkalis etc.
They are insoluble in water. E.g., Myosan (from
myosin), Elestan (from elastin).
b) Meta proteins: These are the second stage
products of protein hydrolysis by treatment with
slightly stronger acids and alkalis. E.g., acid and
alkali metaproteins.
c) Coagulated proteins: These are the denatured
proteins produced by agents such as heat, acids,
alkalis etc, E.g., cooked proteins, coagulated
albumin (egg white ).
Derived proteins (Secondary)
These are the degraded (due to breakdown of peptide
bonds) products of proteins.
a) Proteoses or albumoses: These are hydrolytic products
of proteins which are soluble in water and coagulated by
heat and precipitated by saturation with ammonium
sulphate.
b) Peptones:These are hydrolytic products of proteoses.
They are soluble in water, not coagulated by heat and
not precipitated by saturation with ammonium sulphate.
They can be precipitated by phosphotungstic acid.
c) Peptides: Peptides are composed of very small number
of amino acids joined as peptide bonds. They are named
according to the number of amino acids present in them.
Their types are discussed already.