14 nucleotide metabolism 2014-2015

7/24/2019 14 Nucleotide Metabolism 2014-2015

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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)


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Purines:

Pyrimidines:


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Other nucleotide-containing biomolecules

1. Nucleotide triphosphates

- ATP, GTP, CTP, UTP

5

1


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


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3. Enzyme cofactors- ADP is a structural component in many enzyme cofactors

Co-enzyme A (CoA)

Examples: Co-enzyme A (for transfer of fatty acyl groups)

NAD(P)+and FAD (for electron transfer reactions)


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FAD


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Degradation of nucleic acids

(recycling of intact bases)

NTPs, Co-enzyme A,

NAD(P)+, FAD, etc.

Phosphate

removal

Sugar

removal


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Catabolism of purine nucleotides (AMP and GMP)

GMP

Guanosine

AMP

Adenosine

Inosine

Phosphate removal

Phosphate removal

Sugar removal Sugar removal

Deamination of adenine

[Excreted in

urine in human]


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Degradation of uric acid in different organisms


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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

Allopurinola drug for treatment of GOUT


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Catabolism of purine nucleotides (AMP and GMP)

GMP

Guanosine

AMP

Adenosine

Inosine

Phosphate removal

Phosphate removal

Sugar removal Sugar removal

Deamination of purine

Inhibition by

oxypurinol


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Catabolism of pyrimidine nucleotides (CMP, UMP, dTMP)

CMP Cytidine Uridine

Deamination

of pyrimidine

No excretory products are formed from

pyrimidine catabolism (carbon skeleton)

Phosphate

removal

Sugar

removal

UMP

Phosphate

removal

dTMP

Thymidine

Sugar

removal

Phosphate

removal


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Salvage of purines

Inter-conversions of purine nucleotides and their constituents:


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Salvage of pyrimidines

Inter-conversions of pyrimidine nucleotides and their constituents:


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Biosynthesis of new purines

- 1ststep: formation of 5-phosphoriboxyl 1-pyrophosphate (PRPP)

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


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Azaserine,

Acivicin

(anti-cancer drugs)from

glutamine

R5P = ribose 5-phosphate

Purine ring is formed


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Formation of AMP and GMP from IMP:


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Biosynthesis of new pyrimidines

The ring structure is assembled before attachment of ribose phosphate:


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Formation of UTP:

Pyrimidine ring is formed

PRPP: 5-phosphoriboxyl 1-pyrophosphate

Attachment of ribose 5-phosphate


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Formation of CTP from UTP:


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Formation of dTMP from UMP:

Flurouracil

Methotrexate,

Amphopterin

(anticancer drugs)


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Biosynthesis of Deoxyribonucleotides

14 nucleotide metabolism 2014-2015

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