Nucleotide metabolism

Nucleotides

- Monomeric unit of nucleic acids (DNA and RNA)

- 3 structural components: Ribose, Base, Phosphate

Nucleotide or 5-mononucleotide
(e.g. AMP, GMP, CMP, UMP, dTMP)

Purines:

Pyrimidines:

Other nucleotide-containing biomolecules

1. Nucleotide triphosphates
- ATP, GTP, CTP, UTP

2. Signaling molecules
- cAMP, cGMP, ppGpp
- Induce molecular changes inside cells

3. Enzyme cofactors
- ADP is a structural component in many enzyme cofactors
Examples: Co-enzyme A (for transfer of fatty acyl groups)
NAD(P)+ and FAD (for electron transfer reactions)

Co-enzyme A (CoA)

FAD

Degradation of nucleic acids

NTPs, Co-enzyme A,
NAD(P)+, FAD, etc.

Phosphate
removal

Sugar
removal

(recycling of intact bases)

Catabolism of purine nucleotides (AMP and GMP)

AMP
Phosphate removal
Adenosine
Deamination of adenine
Inosine
Sugar removal

GMP
Phosphate removal
Guanosine
Sugar removal

[Excreted in
urine in human]

Degradation of uric acid in different organisms

GOUT
-

A disease characterized by elevated levels of uric acid (poorly soluble)

May be associated with high-nucleotide diets
Accumulation of sodium urate crystals
Painful joint inflammation

Allopurinol a drug for treatment of GOUT

Catabolism of purine nucleotides (AMP and GMP)

AMP
Phosphate removal
Adenosine
Deamination of purine
Inosine
Sugar removal

Inhibition by
oxypurinol

GMP
Phosphate removal
Guanosine
Sugar removal

Catabolism of pyrimidine nucleotides (CMP, UMP, dTMP)

CMP

Phosphate
removal

Cytidine

Deamination
of pyrimidine

Uridine

Sugar
removal

Phosphate
removal

UMP

No excretory products are formed from

pyrimidine catabolism (carbon skeleton)

Sugar
removal

Thymidine

Phosphate
removal

dTMP

Salvage of purines
Inter-conversions of purine nucleotides and their constituents:

Salvage of pyrimidines
Inter-conversions of pyrimidine nucleotides and their constituents:

Biosynthesis of new purines

-

1st step: formation of 5-phosphoriboxyl 1-pyrophosphate (PRPP)

The purine ring is assembled around the N attached to the ribose phosphate

Azaserine,
Acivicin
(anti-cancer drugs)
from
glutamine
R5P = ribose 5-phosphate

Purine ring is formed

Formation of AMP and GMP from IMP:

Biosynthesis of new pyrimidines

The ring structure is assembled before attachment of ribose phosphate:

Formation of UTP:

Attachment of ribose 5-phosphate

PRPP: 5-phosphoriboxyl 1-pyrophosphate

Pyrimidine ring is formed

Formation of CTP from UTP:

Formation of dTMP from UMP:

Flurouracil

Methotrexate,
Amphopterin
(anticancer drugs)

Biosynthesis of Deoxyribonucleotides