Biosynthesis of Purine Nucleotides

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BIOSYNTHESIS OF PURINE NUCLEOTIDES|
Amphibolic intermediates
Phosphoribosylation of purines
Phosphoribosylation of purine nucleotides
(SALVAGE REACTIONS)
(DE NOVO BIOSYNTHESIS)

DE NOVO BIOSYNTHESIS : Eleven Enzyme Catalyzed Reactions | 1. A-d-ribose-5-phosphate (amphibolic intermediate) PRPP (PRPP synthase) 2. PRPP 5-phospho-B-D-ribosylamine (Glutamyl amidotransferase) 3. 5-PBDR Glycinamide ribosyl-5-phosphate (Glycine transamidase) 4. GR5P Formyl glycinamide ribosyl-5-phosphate (Formyl transferase) 5. FGR5P Formyl glycinamidine ribosyl-5-phosphate (Synthetase VI) 6. FGnR5P Aminoimidazole ribosyl-5-phosphate (Synthetase Vii) 7. AI5P Aminoimidazole caroxylate ribosyl-5-phosphate (caroxylase) 8. AICR5P Aminoimidazole succinyl carboxamide ribosyl-5-phosphate (Synthetase IX) 9. AISCR5P Aminoimidazole carboxamide ribosyl-5-phosphate (Adenylosuccinase) 10. AICR5P Formiminoimidazole carboxamide ribosyl-5-phosphate (Formyl transferase) 11. FICR5P Inosine monophosphate (IMP) (IMP cyclohydrolase) 12.

|
INHIBITOR| REACTION|
antifolate| Formyl transferase (rxns 4 & 10)|
Azaserine | Synthase VI|
Diazanor leucine| PRP glutamyl amidotransferase|
6-mercaptopurine| Adenylosuccinase IMP dehydrogenase|
Mycophenolic acid| IMP dehydrogenase|

SALVAGE PATHWAY OF PURINE NUCLEOTIDE BIOSYNTHESIS : Require far less energy than De Novo counterpart| I. Purine + +**PRPP purine mononucleotide
**product of reaction 2 in de novo biosynthesis
PRPP
AMP
adenosine
Pi

PRPP
IMP
hypoxanthine
Pi
HGPRT

PRPP
GMP
guanine
Pi
PRPP
Pi

II. GMP
adenosine
ADP
ATP
Adenosine kinase
Purine ribonucleoside + ATP purine mononucleotide

FEEDBACK REGULATION|
I. Biosynthesis of IMP
A. PRPP concentration – A function of :
1. Rate of synthesis
2. Rate of utilization
3. Rate of degradation
*major determinants of rate of De...
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