Peshawar Medical College

Nucleotides

Peshawar Medical College

Learning objectives

 To explain what are nucleosides & nucleotides

 To describe the components of nucleotides

 To underline the functions of nucleotides

Peshawar Medical College

Nucleosides and nucleotides
(Components = Base + Sugar + Phosphate)

1. Bases
 Nitrogenous, heterocyclic bases (purines & pyrimidines)
 Numbering – in opposite direction
 Single letter abbreviation (e.g. A,U)

Peshawar Medical College

Nucleosides and nucleotides
(Components = Base + Sugar + Phosphate)

Purine bases Pyrimidine bases

Peshawar Medical College

Tautomerism (keto-enol tautomerism)

amino form & oxo (keto) form

 
imino form & enol form

 Amino & oxo (keto) forms are predominant under

physiologic conditions (suitable for base pairing)
Peshawar Medical College
Uncommon pyrimidine & purine bases

Peshawar Medical College

Components

2. Pentose sugar
Ribose De-oxy-ribose
 Ribose or
de-oxy-ribose

 Numbering with prime

 Prefix “d” is used for

deoxy sugar

Peshawar Medical College

Components

3. Phosphate group attached to ( C5 or C3 of sugar)

through ester linkage

OH O-
 - H+ 
HO – P = O HO – P = O
 
OH OH

Peshawar Medical College

Formation of Nucleotide

 -N-glycosidic Phospho-ester-linkage
NB + Sugar linkage sugar–NB P –Sugar–NB
(nucleoside) PO4 Nucleotide or
Nucleoside- P

Adenine + ribose + phosphate = AMP

(Adenosine mono-phosphate)

dAMP & dGMP (DNA)

Peshawar Medical College

Syn & Anti configuration

Both “syn” and “anti” configurations occur in nucleotides

in nature but “anti” configuration predominates
(suitable for base pairing)

Peshawar Medical College

 Bases, Nucleosides & Nucleotides

Base

Adenine

Guanine

Peshawar Medical College

 Bases, Nucleosides & Nucleotides

Cytosine

Uracil

CH3 CH3

Thymine
Thymidine Thymidine monophosphate (TMP)

Peshawar Medical College

Polymerization of Mono-nucleotides

 Mono-nucleotides are linked by 3  5 phospho-

diester bonds to form polynucleotides (having 5-end
on the left side and 3-end on right)

 Written as
pG pG pA pC pT pA pA pC
Or
5  G G A C T A A C  3

Peshawar Medical College

Functions

 Monomeric units or building blocks of nucleic acids

(RNA, DNA)

 Energy-rich compounds (ATP, GTP)

 Components of coenzymes (NAD, FAD, Co-A)

 Involved in phosphate transfer reactions

(Glucose + ATP → Glucose-6-phosphate + ADP)

Peshawar Medical College

Functions

 Involved in methyl transfer reactions

(S-adenosyl-methionine)

 Serve as donors of sugars (UDP-Gal, UDP-GUA)

(biosynthesis of di- , oligo- , polysaccharides, GAGs)

 Sulfate transfer reactions (PAPS or “active sulfate”)

(Phospho-adenosine-phospho-sulfate)

Peshawar Medical College

Functions

 Serve as donors of lipids (CDP-acyl glycerol)

(lipid biosynthesis)

 Inter-conversion of sugars
(UDP–Glucose  UDP – Galactose)

 Serve as second messengers (cAMP, cGMP)

 Conjugation reaction (UDP-glucuronic acid)

Peshawar Medical College

Functions

 Regulatory function
 Control oxidative phosphorylation (through ADP)
 ATP inhibits PFK-1 activity

 As therapeutic agents (synthetic analogs)

 To inhibit growth of cancer cells (Fluoro-uracil)
 Treatment of gout (Allopurinol – a purine analog)
 Treatment of AIDS
 Suppressors of immune response during organ
transplantation
Peshawar Medical College