NUCLEIC ACIDS CHEMISTRY
Dr. Pinaki Saha
MD(Biochemistry)
BASIC STRUCTURE OF A NUCLEOTIDE
Three structural components: a heterocyclic
compound termed nitrogenous base, a five carbon
(pentose) sugar, and at least one phosphate
group.
The nitrogenous bases belong to one of the
heterocyclic groups, either purines or pyrimidines.
When the nitrogenous bases are combined with a
pentose sugar, they are known as nucleosides.
Phosphate group can be attached either at the 5′-
position or the 3′-position of the pentose, and the
nucleoside-phosphate thus formed is known as
nucleotide.
Nucleic acids are polymers of several nucleotide
units, hold together by covalent linkages
NITROGENOUS BASES
The bases are derivatives of purines or pyrimidines.
Structures of the parent compounds of purine and
pyrimidine bases (which do not occur in nature) are
shown in Figure, with the atoms numbered.
Purines are numbered in anti-clockwise direction, and
the pyrimidines are numbered in the clockwise
direction.
STRUCTURE OF PURINES.
COMMON PYRIMIDINES.
MINOR BASES SEEN IN NUCLEIC
ACIDS
THYMINE is the base present in DNA
THIAMINE is a member of vitamin B
complex
BASES IN DNA AND RNA
There are five major bases:
Adenine, Guanine (purines)
Cytosine, Uracil, Thymine (pyrimidines)
Thymine is present only in DNA, and uracil
only in RNA
SOME OTHER BASES
Some minor or unusual bases are found in nucleic
acids, mostly in RNA. These include 5′-
methylcytosine, pseudouracil, N6 -methyladenine
and N7 –methylguanine
Finally, some methylated purine bases are found in
plants. These include alkaloids like theophylline (1,3-
dimethylxanthine), caffeine (1,3,5-trimethylxanthine)
and theobromine (3,7-dimethylxanthine)
Theophylline is found in tea, and is used
therapeutically in asthma; caffeine is a component of
coffee beans and tea, that elevates intracellular
cAMP level; and theobromine is found in chocolate,
and is a diuretic, heart stimulant and vasodilator
CHEMICAL PROPERTIES OF BASES
Nitrogenous bases include highly conjugated
double bond systems within the ring structures.
For this reason, nucleic acids have a very strong
absorption maximum at about 260 nm, which is
used for nucleic acid quantitation.
Heterocyclic rings of both purines and
pyrimidines have oxo (-C =O-) functional group.
Therefore, a given base can exist in two
tautomeric forms, the lactam or keto form and
the lactim or enol form.
In DNA and RNA, the keto forms are by far more
predominant, and this property makes it
possible for the bases to form intermolecular
hydrogen bonds
PENTOSE SUGARS
The 5-carbon sugar found in nucleotides is
either D-ribose or D-2′-deoxyribose. Each
occurs in furanose form, the configuration at
C-1 being β
D-Ribose is present in RNA, while D-2′-
deoxyribose is present in DNA.
Deoxyribose, as the name suggests, differs
from ribose in having one oxygen less (at C-
2)
NUCLEOSIDES
A nucleoside is a compound of base and sugar linked
by a N-glycosidic linkage (a carbon-nitrogen bond).
The bond is formed between C-1 of sugar and
nitrogen atom 1 of pyrimidine base or nitrogen atom
9 of purine base.
If the sugar is ribose, the compound is ribonucleoside
and if the sugar is deoxyribose, the compound is
deoxyribonucleoside.
Adenosine (adenine +ribose), guanosine (guanine +
ribose), cytidine (cytosine +ribose) and uridine (uracil
+ribose) are the ribonucleosides of A, G, C and U,
respectively. Similarly, deoxyadenosine,
deoxyguanosine, deoxycytidine and deoxythymidine
are the deoxyribonucleosides of A, G, C and T,
respectively
NUCLEOTIDES
Nucleotide is nucleoside plus phosphate.
The phosphate group is esterified to one of
the hydroxyl groups of the sugar component
of the nucleoside. Mostly it is the hydroxyl
group at the C-5 (less commonly C-3) that is
phosphorylated.
To avoid confusion between the numbering of
various atoms in the base and carbon atoms
of the sugar, the latter are represented with
an associated prime. Thus, carbons of sugar
are numbered 1′, 2′, 3′ etc.
NOMENCLATURE
The nucleotides are named as phosphate
derivatives of nucleosides. Thus, adenosine linked
covalently with phosphate produces adenosine
monophosphate (AMP). It is a mononucleotide.
Likewise, other mononucleotides, e.g. guanosine
monophosphate (GMP), cytidine monophosphate
(CMP), and uridine monophosphate (UMP) are
formed by phosphorylation of guanosine, cytidine
and uridine, respectively.
NUCLEOSIDE MONOPHOSPHATE
The phosphate group can be attached either at the
5′-position or the 3′-position of the pentose, and
accordingly the mononucleotides formed are
designated as 5′or 3′-monophosphates, respectively.
However, attachment at the 5′-position is far more
common, and therefore 5′ is usually omitted in the
abbreviation. Thus, AMP means adenosine 5′-
monophosphate, CMP means cytidine 5′-
monophosphate, and so on.
However, for adenosine 3′-monophosphate or
cytidine 3′-monophosphate, the abbreviations 3′-
AMP or 3′-CMP respectively are used. A
mononucleotide is also called nucleoside
monophosphate
NUCLEOSIDE-DIPHOSPHATE AND
TRIPHOSPHATE
Additional phosphate groups may be
attached to a mononucleotide. Addition of a
second and a third phosphate to a nucleoside
monophosphate yields a nucleoside-
diphosphate, and triphosphate, respectively.
AMP thus yields adenosine diphosphate
(ADP) or adenosine triphosphate (ATP),
respectively. The subsequent phosphate
groups are attached to the preceding ones by
acid anhydride bonds. These bonds possess
high free energy of hydrolysis, yielding more
than 7 kcal/ mole of free energy
FUNCTIONS
Nucleotides are central to maintenance and
propagation of life. They are most versatile of all
biomolecules, being involved in a number of
reactions including the energy transfer reaction
The ribonucleotides such as ATP, GTP, CTP and
UTP are important coenzymes and provide the
basic unit of RNA. The deoxyribonucleotides,
dATP, dGTP, dCTP and dTTP are required for DNA
replication and DNA repair.
Nucleoside sugars are activated precursors which
are used in biosynthetic reactions. For example:
UDP-glucose is used in glycogen synthesis, UDP-
galactose is used in synthesis of ceramides, CTP-
choline is used in phospholipid synthesis
FUNCTIONS
Nucleotides are the basis of high-energy compounds.
The best known example is adenosine triphosphate
(ATP), referred to as the currency of free energy in the
body, which provides energy for all types of cellular
activities. GTP is used as an energy source in protein
synthesis.
Regulation of enzyme activity involves certain
nucleotides, such as cAMP and cGMP. They are signal
conducting molecules, acting as intracellular
messengers for certain hormones
The nucleic acids, DNA and RNA, are involved in
storage and decoding of genetic information.
The coenzymes, NAD⁺, FAD and coenzyme A have
nucleotides as essential components of their
structures
DEGRADATION AND ABSORPTION
Although dietary nucleotides and nucleic acids are
digested to nucleosides and free bases, the
degradation products are poorly absorbed.
The small amounts of absorbed products are not
delivered to tissues but rather degraded within
intestinal mucosa to form uric acid.
Thus, dietary nucleic acids are not used for the
synthesis of tissue nucleic acids
The ribonucleotides are present in millimolar con
centrations in the cell, and the
deoxyribonucleotides are present in micromolar
concentrations intracellularly
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