Nucleotides are organic compounds that serve as the monomeric units of nucleic acids DNA and RNA. They consist of three components - a phosphate group, a 5-carbon sugar (ribose or deoxyribose), and one of five nitrogenous bases (adenine, guanine, cytosine, thymine, or uracil). Nucleotides function as carriers of chemical energy in cells and participate in cellular signaling and enzymatic reactions. They are the building blocks that make up nucleic acids, with DNA containing the bases adenine, guanine, cytosine and thymine, and RNA containing adenine, guanine, cytosine and uracil instead of thymine. Nucleotides differ based on their
2. Introduction
• Nucleotides are organic compounds made up of a PO4
group, nitrogenous base & a sugar molecule.
• These are the building blocks of nucleic
acids (DNA and RNA).
• They serve as sources of chemical energy (ATP, GTP),
participate in cellular signalling (cAMP, cGMP) and
function as important cofactors of enzymatic reactions
(coA, FAD, FMN, NAD+).
3. HISTORY
In 1869, Miescher discovered "nuclein" (DNA) in the
cells from pus & later he separated it into a protein and
an acid molecule. It came to known as nucleic acid after
1874.
1926 , Levene proposed “Tetra nucleotide theory”
which states that Nucleic acid consists of only 4 nitrides
as it gives 4 diff nucleotides on hydrolysis.
4. In 1950, Erwin Chargaff shows that the four
nucleotides are not present in nucleic acids in
stable proportions.
1957, Sir Alexander R.Todd of Cambridge
University gave structure of nucleotide.
7. Bases
• Purines :
– Adenine (A)
– Guanine (G)
• Pyrimidines :
– Cytosine (C)
– Uracil (U)
– Thymine (T)
• The bases are abbreviated by their first letters (A, G, C, T, U).
• The purines (A, G) occur in both RNA & DNA.
• Among the pyrimidines, C occurs in both RNA & DNA, but
• T occurs in DNA, and U occurs in RNA.
• DNA: A,G,C,T
• RNA: A,G,C,U
8.
9. Some minor bases:
Minor bases of DNA Minor bases of RNA
• 5-Methylcytidine occurs in DNA of animals and
higher plants.
• N6-methyladenosine occurs in bacterial DNA.
11. Nucleotides = nucleoside + phosphate
A nucleotide is a nucleoside with one or more phosphate groups
bound covalently to the 3rd or 5th hydroxyl group of pentose sugar. Most
of nucleoside phosphate involve in biological function are 5’- phosphates.
Since 5’- phosphates are most often seen, they are written without any
prefix.
13. NOMENCLATURE:-
• Nucleosides phosphorylated on the 3’ or 5’ C of
ribose are termed ; nucleoside 3’-
monophoshate & nucleoside 5’- monophoshate.
• ‘5’ is by convention omitted when naming
nucleotide.
• Abbrevations such as AMP, GTP denotes the
phosphate is esterified to 5’ of pentose.
• Additional phosphate group is attached to
preexisting phosphate of mononucleotide ,
- nucleotide diphosphate – ADP
- nucleotide triphosphate – ATP
16. Individual properties :-
PROPERTIES OF PURINE BASES:-
Sparingly soluble in water
Absorb light in UV region at 260 nm.
(detection & quantitation of nucleotides)
Capable of forming hydrogen bond
17. Properties of pyrimidine bases :-
Soluble at body pH
Also absorb UV light at 260 nm
Capable of forming hydrogen bond
18. Pyrimidine base :-
Aromatic base atoms are numbered 1 to 6 for pyrimidine
Atoms or group attached to base atoms have same
number as the ring atom to which they are bonded
22. PURINE BASES :-
Aromatic base atoms numbered 1 to 9
Purine ring is formed by fusion of pyrimidine ring
with imidazole ring
Numbering is anticlockwise
27. ATP (ADENOSINE TRIPHOSPHATE)
• Many synthetic reactions requires energy, e.g.
arginosuccinate synthetase reaction in urea cycle.
• ATP is required for the synthesis of Phospho creatine from
creatine, synthesis of FA from acetyl CoA, formation of
glucose from pyruvic acid, etc.
• ATP is an important source of energy for muscle contraction,
transmission of nerve impulses, transport of nutrients
across cell membrane, motility of spermatozoa.
• ATP is required for the formation of active methionine, which
is required for methylation reaction
• ATP donates phosphate for a variety of phosphotransferase
reactions e.g., hexokinase reaction.
32. ADENOSINE DI PHOSPHATE (ADP)
• ADP plays an important role as a primary PO4
acceptor in oxidative phosphorylation and muscle
contraction, etc
• ADP is also important as an activator of the enzyme
glutamate dehydrogenase
34. ADENOSINE MONO PHOSPHATE
(AMP)
• In the glycolytic pathway, the enzyme
phosphofructokinase is inhibited by ATP but the
inhibition is reversed by AMP.
• AMP can also act as an inhibitor of certain enzymes
like fructose-1-6- bisphosphatase and
adenylosuccinate synthetase.
• In resting muscles, AMP is formed from ADP, by
adenylate kinase, the AMP produced activates the
phosphorylase b enzyme of muscle and increase
breakdown of glycogen.
36. URIDINE NUCLEOTIDES
• UTP also has the role of a source of energy or an activator of
substrates in metabolic reactions, like that of ATP, but more
specific.
• When UTP activates a substrate, UDP-substrate is usually
formed and inorganic phosphate is released. UDP-
glucose enters the synthesis of glycogen.
• UTP is used in the metabolism of galactose, where the
activated form UDP-galactose is converted to UDP-glucose
• UDP-glucuronate is used to conjugate bilirubin to a more
water-soluble bilirubin diglucuronide
41. Miscellaneous :-
PAPS - Phospho Adenosine Phospho
Sulphate
(active sulphate) formed in liver
Sulfates enzymes which catalyze
introduction of SO4 group
In biosynthesis of chondroitin sulfate
Formation of sulpholipids
SAM:- S- Adenosyl Methionine
48. FUNCTIONS
• c-GMP is second messenger in photo
transduction in the eyes.
• It has been claimed that c-GMP as second
messengers regulate the closing and opening of
Na+ channels. In the dark there are high levels
of c-GMP which bind to Na+ channels causing
them to open. Reverse occur in light.
49. INOSINE MONOPHOPHATE
• Hypoxanthine ribonulcleotide, usually called
IMP is a precursor of all purine nucleotide
synthesized de-novo
• Inosinate can also be formed by de amination
of AMP, a reaction which occurs particularly in
muscles as a part of purine nucleotide cycle
50. SYNTHETIC ANALOGUES OF
BIOMEDICAL IMPORTANCE
• Synthetic analogues of nucleobases,
nucleosides and nucleotides are recently of
wide use in medical sciences and clinical
medicine.
• The heterocyclic ring structure or the sugar
moiety is altered in such a way as to induce
toxic effects when the analogues get
incorporated into cellular constituents of the
body.
52. Allopurinol is a purine analogue. This drug is an inhibitor of the enzyme
xanthine oxidase, which inhibit uric acid formation. The drug is widely used
for the treatment of gout
AZT-(azydothymidine):- thymidine analogue treatment of AIDS
(terminates DNA synthesis catalysed by reverse transcriptase of retrovirus
such as HIV)
Uses of some Synthetic analogues of
nucleotides:-
53. NUCLEOSIDE ANALOGUES AS
DRUGS
ANALOGUES DRUGS USES
Deoxyadenosine
analogues
Didanosine,
Vidarabine
HIV
Chemotherapy
Deoxycytidine analogues Cytarabine,
Emtricitabine
Lamivudine
Zalcitabine
Chemothrapy
HIV
Hepatitis B
HIV
Deoxyguanosine
analogues
Abacavir
Entecavir
HIV
Hepatitis B
Deoxy-
thymidine analogues
Stavudine
Telbivudine
Zidovudine
HIV
Hepatitis B
HIV
Deoxyuridine analogues Idoxuridine
Trifluridine
HIV
HIV
54. NUCLEOTIDE ANALOGUES AS
DRUGS
• Tenofovir, also called 'prodrug‘. It is approved
in the USA for the treatment of both HIV and
hepatitis B.
• Adefovir, has trade names Preveon and
Hepsera. It was not approved by the FDA for
treatment of HIV due to toxicity issues, but a
lower dose is approved for the treatment of
hepatitis B.
