NUCLEIC ACIDS

AND
NUCLEOTIDES

1 Nucleic acids
 THE NUCLEIC ACIDS
(DNA and RNA)
Are formed by the polymerization of a
large number of nucleotide units.

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Nucleic acids 3
 NUCLEOTIDES

A nucleotide is a compound that contains a

nitrogenous heterocyclic base (a purine or
a pyrimidine)

connected to a phosphorylated pentose

sugar units (deoxyribose or ribose)

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 The bases in nucleosides and
nucleotides
The principal purine bases found in the body
are adenine (A), and guanine (G)

Other purine bases include xanthine and

hypoxanthine

Pyrimidine bases in the body are cytosine (C),

uracil (U) and thymine (T)

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Nucleic acids 6
 Nucleoside and nucleotide
nomenclature
Both nucleosides and nucleotides are
named after the bases from which they
are derived.
The nucleosides of ribose with
adenine, guanine, cytosine, thymine and
uracil are called adenosine, guanosine,
cytidine, thymidine and uridine

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 NH 2 O O
NH 2

N N N
N N N
9
1 9 1
N N O N H 2N N N O N
HO HO HO HO
O O O O

OH OH OH OH OH OH OH OH

Adenosine Cytidine Guanosine Uridine

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 The corresponding nucleotides are called
adenylic acid or adenosine monophosphate
(AMP), guanilyc acid or guanosine
monophosphate (GMP), cytidilic acid (CMP),
uridylic acid (UTP) and thymidic acid (TMP)

If the oxyribose is present rather than ribose,

the prefix deoxy is used, as in deoxyuridine
(dU) or deoxyuridylic acid (dUMP)

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 Note:
The monophosphorylated form of adenosine
(adenosine-5'-monophosphate) is written as,
AMP. The di- and tri-phosphorylated forms are
written as, ADP and ATP, respectively.
O O
NH 2 NH 2
CH 3
N N N HN HN
N
1 1
N N N N O N O N
O O O O O O O
O O O
P O P O
P P
O O O O O O O O

OH OH OH H OH OH OH H

AMP dAMP UMP TMP

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 Linkage of the base and sugar units

In both nucleosides and nucleotides, the

purine or pyrimidine base is linked to the
pentose sugar by a glycosidic linkage.

The C-1 of the pentose (the anomeric carbon

of the D-ribose or 2'-deoxy-D-ribose) is linked
to the N-1 of the pyrimidine ring or N-9 the
purine ring.

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 The atoms in the sugar unit are numbered
with prime to distinguish the from atoms in the
bases.
It is important to indicate the position at which
esterification of the sugar has occurred e.g.:
Adenosine 3-monophosphate or adenosine
5-monophosphat.
Unless otherwise stated, reference to, for
example, and adenine nucleotide in the text
implies that is a 5- ester.

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 Bases, nucleosides, and nucleotides
Nucleoside Nucleotide, Where
Base
Base Formula X=ribose or X=Ribose
X=H
deoxyribose Phosphate

NH 2
Adenine Adenosine Adenosine
N
N A A monophosphate
N N
9

AMP
X

O
H N Guanine Guanosine Guanosine
N
G G monophosphate
H 2N N N GMP
X

NH 2
Cytosine Cytidine Cytidine
N
C C monophosphate
O N CMP
X
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 Nucleoside Nucleotide, Where
Base
Base Formula X=ribose or X=Ribose
X=H
deoxyribose Phosphate

O
H Uracil Uridine Uridine
N monophosphate
U U
O N UMP
X

O
H CH 3 Thymine Thymidine Thymidine
N
T T monophosphate
O N TMP
dX

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 Nucleosides are found in the cell primarily in
their phosphorylated form. These are termed
nucleotides.
NH 2 NH 2

N N
N N
9 9

N N N N
HO HO
O O

OH OH OH OH

syn- Adenosine anti -Adenosine

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 The nucleotides found in DNA are unique
from those of RNA in that the ribose
exists in the 2'-deoxy form and the
abbreviations of the nucleotides contain a
d designation.
The monophosphorylated form of
adenosine found in DNA
(deoxyadenosine-5'-monophosphate) is
written as dAMP.
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Nucleic acids 17
Nucleic acids 18
 The nucleotide uridine is never found in DNA
and thymine is almost exclusively found in
DNA.
Thymine is found in tRNAs but not rRNAs nor
mRNAs.
There are several less common bases found in
DNA and RNA.
The primary modified base in DNA is 5-
methylcytosine.
A variety of modified bases appear in the tRNAs.
Many modified nucleotides are encountered
outside of the context of DNA and RNA that
serve important biological functions.

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 Polynucleotides
Polynucleotides (e.g. DNA and RNA) are formed
by the condensation of more nucleotides.

The condensation most commonly occurs

between the alcohol of a 5'-phosphate of one
nucleotide and the 3'-hydroxyl group of a
second (adjacent nucleotide), with the
elimination of H2O, forming a phosphodiester
bond.

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 The formation of phosphodiester bonds in DNA
and RNA exhibits directionality.
The primary structure of DNA and RNA (the linear
arrangement of the nucleotides) proceeds
in the 5' ----> 3' direction.
The common representation of the primary
structure of DNA or RNA molecules is to write the
nucleotide sequences from left to right
synonymous with the 5' -----> 3' direction as
shown:
5'- pG pA pT pC - 3'

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 Structure of DNA
Utilizing X-ray diffraction data, obtained
from crystals of DNA, James Watson and
Francis Crick proposed a model for the
structure of DNA.
This model (subsequently verified by
additional data) predicted that DNA would
exist as a helix of two complementary anti
parallel strands, wound around each other
in a rightward direction and stabilized by
H-bonding between bases in adjacent
strands.
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Nucleic acids 23
 In the Watson-Crick model, the bases are in the
interior of the helix aligned at a nearly 90 degree
angle relative to the axis of the helix.
Purine bases form hydrogen bonds with
pyrimidines, in the crucial phenomenon of base
pairing.

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 Experimental determination of molecule of DNA
has shown the concentration of adenine (A) is
equal to thymine (T) and the concentration of
cytidine (C) is equal to guanine (G).
This means that A will only base-pair with T, and
C with G.
According to this pattern, known as Watson-
Crick base-pairing, the base-pairs composed
of G and C contain three H-bonds, whereas
those of A and T contain two H-bonds.
This makes G-C base-pairs more stable than A-
T base-pairs.

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 (a) Base pairing A-T and G-C in the
Watson-Crick model of DNA
(b) Distance between the base pair.
The base shows the 0.34 nm
distance between them.

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 The antiparallel nature of the helix stems from
the orientation of the individual strands.
From any fixed position in the helix, one strand
is oriented in the 5' ---> 3' direction and the
other in the 3' ---> 5' direction.
5 C-G-A-T-A-G 3
3 G-C-T-A-T-C 5

On its exterior surface, the double helix of DNA

contains two deep grooves between the ribose-
phosphate chains.
These two grooves are of unequal size and
termed the major and minor grooves.

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Nucleic acids 28
 The difference in their size is due to the
asymmetry of the deoxyribose rings and the
structurally distinct nature of the upper surface
of a base-pair relative to the bottom surface.

The double helix of DNA has been shown to

exist in several different forms, depending upon
sequence content and ionic conditions of crystal
preparation.

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 IMPORTANT BIOLOGICAL
FUNCTION OF NUCLEOTIDES
Nucleotides have a number of important
functions:
precursor units for the synthesis of the
nucleic acids DNA and RNA
linkage of energy yielding reactions to those
which require energy
activated intermediates in many biosynthetic
processes
synthesis of important coenzymes metabolic
regulation
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 MEDICAL APPLICATIONS OF
NUCLEOBASES, NUCLEOSIDES AND
NUCLEOTIDES

Synthetic analogues of naturally occurring

nucleobases, nucleosides or nucleotides that
can act as enzyme inhibitors or replace naturally
occurring nucleotides in nucleic acids are
increasingly being used in the chemotherapy of
cancer and certain other clinical conditions.

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 CANCER CHEMOTHERAPY
Example of synthetic analogues used in cancer
chemotheraphy include 5-fluorouracil, 6-
mercaptopurine, and cytosine arabinoside.

ANTIFUNGAL AGENTS
Flucytosine (5-fluorocytosine) acts as an
antifungal agent through convertion to 5-
fluoroacil in the fungal cells.

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 ANTIVIRAL AGENTS
Idoxuridine (iododeoxyuridine) is effectively used in
the treatment of corneal infections by herpes virus.
It acts as a competitive inhibitors (via
phosphorylated derivatives) of the incorporation of
thymidylic acid into DNA.

TREATMENT OF HYPERURICAEMIA AND GOUT

Allopurinol (4-hydroxypyrazolopyrimidine), a
structural analogue of hypoxanthine is widely used
as an inhibitor of de novo purine biosynthesis, and
of xanthine oxidase.

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 References:
Ahmad, Mushtaq Essentials of Medical
Biochemistry, Vol. 1, 6th ed. Merit Publishers,
Multan, 1999.
Lehninger, A.L. Biochemistry: The molecular
basis of cell structure and function, 3rd ed. Worth
Publishers Inc., N.Y., 1993.
Murray, R.K., Granner. D.K., Mayes, P.A., and
Rodwell, V.W. (eds) Harpers Biochemistry,
24th ED. Appleton and Lange, California, 1996.
Stryer, L. Biochemistry, 4th ed. W.H. Freeman
and Co., N.Y., 1995.

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