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Nucleotides Metabolism
by
Hassan Mokhamer
Sources Of Atoms in purines
Synthesis Of Purines nucleotides
De Novo Pathway(Steps)
• 1. Synthesis of 5’_ phosphoribosyl-1-pyrophosphate(PRPP)
The key regulatory enzyme is phosphoribosyl pyrophosphate synthase
PRPP Synthase
Ribose-5-Phosphate 5-Phosphoribosyl -1-pyrophosphate
ATP AMP
2. Synthesis of 5’_ phosphoribosylamine
H2O PPi
Glutamine Glutamate
• 3. Synthesis of Inosine 5’- Monophosphate (IMP):
O
C N
HN C
Glycine 4
CH
Folic Acid HC C 5
Glutamine N
5-Phosphoribosylamine N
Aspartate 2-
O3P O CH2 O
CO2 H H
H H
OH OH
IMP
Xanthosine GMP GDP GTP
Monophosphate
Inhibitors of purines synthesis
Methotrexate
That competitively inhibits the reduction of
dihdrofolate to tetrahydrofolate . Thus this drug
will limit the amount of tetrahydrofolate available
for use in purine synthesis
Conversion of ribonucleotides to deoxyribonucleotides
Ribonucleotide Reductase
Thioredoxin Reductase
NADP+ NADPH + H+
Catabolism of purine nucleotides
• b) Allopurinol:
it is a structural analogue of hypoxanthine that
competitively inhibits xanthine oxidase enzyme
decreasing formation of uric acid
Metabolism of pyrimidine nucleotides
Orotic Acid
CTP UTP
UDP UMP