DR.

ABHAY KUMAR
DR. PRAKHAR TIWARI
There are approximately 300 amino acids present in
various animal, plant and microbial systems, but only
20 amino acids are involved in the formation of
proteins.
• All the 20 amino acids found in proteins
have a carboxyl group (-COOH) and an amino acid
group (-NH2) bound to the same carbon atom called
 the α-carbon The 20 amino acids of proteins are often
referred to as the standard or primary or normal
amino acids.
Essential amino acids cannot be synthesized by the
body
and must, therefore, be essentially supplied through the
diet. Ten amino acids, essential for humans include:
• Phenylalanine • Methionine
• Valine • Histidine
• Threonine • Arginine
• Tryptophan • Lysine
• Isoleucine • Leucine.
The mnemonics often used by students are PVT.
TIM. HALL
Among the ten essential amino acids; arginine
and
histidine are known as semi-essential amino
acids since
these amino acids are synthesized partially in
human body.
Arginine and histidine become essential in diet
during
periods of rapid growth as in childhood and
pregnancy.
• Formation of proteins: Amino acids are joined to
each
other by peptide bonds to form proteins and peptides.
• Formation of glucose: Glucogenic amino acids are
converted to glucose in the body.
• Enzyme activity: The thiol (-SH) group of cysteine
has an important role in certain enzyme activity.
• Transport and storage form of ammonia: Amino acid
glutamine plays an important role in transport and
storage of amino nitrogen in the form of ammonia.
• As a buffer: Both free amino acids and some
amino acids
present in protein can potentially act as buffer, e.g.
histidine
can serve as the best buffer at physiological pH.
• Detoxification reactions: Glycine, cysteine and
methionine are involved in the detoxification of
toxic substances.
• Formation of biologically important
compounds:
Specific amino acids can give rise to specific
biologically important compounds in the body
Every protein in its native state has a unique three
dimensionalnstructure which is referred to as its
conformation and made up of only 20 different amino
acids.
The number and sequence of these amino acids
are different in different proteins. Protein structure can
be classified into four levels of organization:
1. Primary structure
2. Secondary structure
3. Tertiary structure
4. Quaternary structure.
• The sequence of amino acids forming the backbone
of proteins and location of any disulfide bond in a
protein is called, the primary structure of the protein

• In proteins, amino acids are joined covalently by

peptide bonds, which are formed between α-carboxyl
group of one amino acid and α-amino group of
another with the elimination of a water molecule
. Linkage of many amino acids through peptide bonds
results in an unbranched chain called a polypeptide
. Each amino acid in a polypeptide is
called a residue or moiety. Each polypeptide
chain
is having free amino group at one end called
Nterminal
and free carboxyl group at another end,
called C-terminal.
• This amino acid sequence of a
protein is referred to as its primary structure.
• For stability of primary structure, hydrogen bonding
between the hydrogen of NH and oxygen of C=O
groups of the polypeptide chain occurs, which gives
rise to folding or twisting of the primary structure.
• Thus, regular folding and twisting of the polypeptide
chain brought about by hydrogen bonding is called
secondary structure of protein. The most important
kinds of secondary structure are:
– α-Helix (helicoidal structure)
– β-Pleated sheet (stretched structure).
It is called α because it was the first structure elucidated
by Pauling and Corey. If a backbone of polypeptide chainis
twisted by an equal amounts about each α-carbon, it
forms a coil or helix. The helix is a rod-like structure.
• The helix is stabilized by hydrogen bonds beween
the NH and CO groups of the same chain.
• These hydrogen bonds have an essentially optimal
nitrogen to oxygen (N-O) distance of 2.8 Å. Thus, CO
group of each amino acid is hydrogen bonded to the
-NH of the amino acid that is situated four residues
ahead in the linear sequence.
• The axial distance between adjacent amino acids is
1.5 Å and gives 3.6 amino acid residues per turn of
helix .
Pauling and Corey discovered another type of structure
which they named β-pleated sheet (β because it was the
second structure they elucidated). The surfaces of
β-sheet appear “pleated” and these structures are
therefore often called “β-pleated sheet’.
• A polypeptide chain in the β-pleated sheet is almost
fully extended rather than being tightly coiled as in
the α-helix.
• Unlike α-helix, β-pleated sheets are composed of two
or more polypeptide chains.
• β-pleated sheet is stabilized by hydrogen bonds
between NH and C=O groups in a different
polypeptide chain whereas in α-helix, the hydrogen
bonds are between NH and CO groups in the same
polypeptide chain.
• The peptide chain, with its secondary structure, may
be further folded and twisted about itself forming
three-dimensional arrangement of the polypeptide
chain .
• Amino acid residues which are very distant from one
another in the sequence can be brought very near
due to the folding and thus form regions essential
for the functioning of the protein, like active site or
catalytic site of enzymes.
• Thus, the three-dimensional folded compact and
biologically active conformation of a protein is
referred to as its tertiary structure, e.g. myoglobin.
• Only those proteins that have more than one
polypeptide chain (polymeric) have a quaternary
structure. Not all proteins are polymeric. Many
proteins consist of a single polypeptide chain and
are called monomeric proteins, e.g. myoglobin.
• The arrangement of these polymeric polypeptide
subunits in three-dimensional complexes is called
the quaternary structure of the protein . Examples of
proteins having quaternary structure
are:
– Lactate dehydrogenase
– Pyruvate dehydrogenase
– Hemoglobin.
• Nucleic acids are polymers of nucleotides, linked by
phosphodiester bond, they are therefore called
polynucleotides.
• The nucleic acids are of two main types:
– Deoxyribonucleic acid or DNA
– Ribonucleic acid or RNA.
• DNA is present in nuclei and small amounts are also
present in mitochondria, whereas 90% of the RNA
is present in cell cytoplasm and 10% in the
nucleolus.
Each nucleotide consists of three components:
1. A nitrogenous base
2. A pentose sugar
3. A phosphate group.
Two classes of nitrogenous bases namely
purines and
pyrimidines are present in RNA and DNA.
Purine Bases
• Two principal purine bases found in DNAs, as
well
as RNAs are:
i. Adenine (A)
ii. Guanine (G). Pyrimidine Bases
• Three major pyrimidine bases are:
i. Cytosine (C)
ii. Uracil (U)
iii. Thymine (T).
• Cytosine and uracil are found in RNAs and
cytosine
and thymine in DNA.
• Both DNA and RNA contain the pyrimidine
cytosine
but they differ in their second pyrimidine base.
DNA
contains thymine whereas RNA contains uracil.
• The pentose sugar is either D-ribose or D-2-
deoxyribose. DNA and RNA are distinguished on the
basis of the pentose sugar present. DNA contains D-2-
deoxyribose and RNA contains D-ribose.
• A pentose sugar (D-ribose or D-2-deoxyribose) is
linked to a base (purine or pyrimidine) via covalent
N-glycosidic bond . The term nucleoside
is used for structures containing only sugar and
nitrogen base.
• This linkage joins nitrogen-9 of the purine base or
nitrogen 1 of the pyrimidine base with carbon 1 of
pentose sugar .
• DNA is a very long, thread like macromolecule made
up of a large number of deoxyribonucleotides.
Deoxyribonucleotide is composed of a nitrogenous
base, a sugar and phosphate group.
• The bases of DNA molecule carry genetic information,
whereas their sugar and phosphate groups perform
a structural role.
• The sugar in a deoxyribonucleotide is deoxyribose.
• The purine bases in DNA are adenine (A), and
guanine (G).
• Pyrimidine bases are thymine (T) and cytosine
(C).
• DNA is a polymer of many deoxyribonucleotides
linked covalently by 3', 5' phosphodiester bonds.
The 3'-hydroxyl group of the sugar moiety of one
deoxyribonucleotide is joined to the 5'-hydroxyl
group of the adjacent sugar moiety of
deoxyribonucleotide
by a phosphodiester linkage .
In 1953, James Watson and Francis Crick deduced the
three-dimensional structure of DNA. The important
features of their model of DNA are as follows:
• Two helical polynucleotide chains are coiled
around a common axis. The chains run in opposite
direction (anti parallel) .
• The purine and pyrimidine bases are on the inside
of the helix, whereas the phosphate and deoxyribose
units are on the outside.
• The diameter of the helix is 20 Å. Adjacent bases are
separated by 3.4 Å along the helix axis and the helical
structure repeates after ten residues on each chain,
i.e. at intervals of 34 Å .
• The two chains are held together by hydrogen bonds
between complementary pairs of bases:
– Adenine is always paired with thymine by formation
of two hydrogen bonds. Guanine is always
paired with cytosine by formation of three
hydrogen bonds .
• The two strands are always complementary to each
other. In a double stranded DNA molecule, the
content of adenine equals to that of thymine and the
contents of guanine equals to that of cytosine. The
complementary base pairing proves the Chargaff’s
rule .
• The model proposed by Watson and Crick is a B
form of DNA (B-DNA) which is a right
handed helix of 10 base pairs per turn, containing
grooves of alternate size, known as major and
minor grooves.
• Other forms of DNA may also occur, such as A-
DNA
and Z-DNA. Under physiologic conditions, DNA is
almost entirely in Watson-Crick B form.
• Ervin Chargaff discovered that in DNA of all species,
quantity of purines is the same as that of pyrimidines
(A+G=T+C). He observed that in DNA, content of
adenine equals that of thymin (A=T) and content of
guanine equals that of cytosine (G=C).
• Watson and Crick deduced that adenine must pair
with thymine and guanine with cytosine, because of
stearic and hydrogen bonding factors. Adenine
cannot pair with cytosine; guanine cannot pair with
thymine.
• Thus, one member of a base pair in a DNA must
always be a purine and the other a pyrimidine.
• This base pairing restriction explains that in a
double
stranded DNA molecule, the content of A equals
that
of T and the content of G equals that of C. • The
ratio of purine to pyrimidine bases in the DNA
is always one, i.e. G+A : T+C = 1. This is that of
Chargaff’s rule.
A prokaryotic cell generally contains a single
chromosome composed of double stranded
circular
DNA, which contains over 4 x 106 base pairs.
Because
DNA molecules are so large, they require special
organization/packaging to enable them to reside
within cells. In E. coli, the circular DNA is
supercoiled and attached to an RNA-protein core.
• Eukaryotes contain over 1,000 times the amount of
DNA found in prokaryotes. Consequently, their
method of organizing or packing DNA is much more
complex.
• A typical human cell contains 46 chromosomes, whose
total DNA is approximately two meter in length.
• The packing of DNA in a chromosome represents
a 10,000 fold shortening of its length from primary
B-form DNA.
• In resting nondividing eukaryotic cells, the
chromosomal material is called chromatin.
Chromatin is made up of nucleosomes.
Different Levels of Organization of Eukaryotic
Unlike double stranded helical structure of DNA,
the
RNAs are single stranded. RNA is an unbranched
linear
polymer of ribonucleotides joined by 3’, 5’
phosphodiester
bonds. The phosphodiester bonds join the 3’-OH
group
of ribose of one nucleotide unit to the 5’-OH group
of
ribose sugar of the next nucleotide.
• In RNA, the sugar is ribose rather than 2'-
deoxyribose
of DNA.
• RNA does not possess thymine except in the
rare
case. Instead of thymine, RNA contains uracil. In
RNA, adenine pairs with uracil rather than
thymine.
• Unlike DNA, RNA is a single stranded and does
not
exhibit the equivalence of adenine with uracil and
cytosine with guanine.
Cell contains three major types of RNA:
1. Messenger RNA (mRNA)
2. Transfer RNA (tRNA)
3. Ribosomal RNA (rRNA).
All of these are involved in the process of
protein
biosynthesis. Each differs from the others by
size and
function.