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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