Phosphoribosyl formylglycineamidine

It may be seen that although diazo-oxo-norleucine is a much more potent inhibitor than azaserine, it is less selective. In contrast, azaserine is 60 times more effective than diazo-oxo-norleucine toward phosphoribosyl formylglycineamidine thetase. These ratios are markedly different when determined with the Salmonella enzyme, however (P). Azaserine, and presumably diazo-oxo-norleucine, bind covalently to a cysteine sulfhydryl of the enzyme, with the loss of the diazo group (10). 

Phosphoribosyl formylglycineamidine synthetase catalyzes the irreversible transfer of the amide group of glutamine to phosphoribosyl formylglycineamide to form the corresponding amidine. The molecular weight of the Salmonella typhimurium and chicken liver enzymes is 135,000 21). 

The cyclization of phosphoribosyl formylglycineamidine requires, in addition to ATP, both Mg + and K+. The reaction is irreversible. This reac-... 

Phosphoribosyl formylglycineamidine synthetase Carbon-nitrogen Glutamine amide transfer No Yes... 

Fig. 15-16 The de novo purine biosynthetic pathway. Rib-5-P, ribose 5-phosphate P-Rib-PP, 5-phosphoribosyl 1-pyrophosphate PRA, 5-phosphoribosylamine IO-CHO-FH4, /Vl0-formyl tetrahydrofolate GAR, glycineamide ribotide FGAR. /V-formylglycineamide ribotide FGAM, /V-formylglycineamidine ribotide AIR, 5-aminoimidazole ribotide CAIR, 4-carboxy-5-aminoimidazole ribotide SAICAR, iV-succino-5-aminoimidazole-4-carboxamide ribotide AICAR, 5-aminoimidazole-4-carboxamide ribotide FAICAR, 5-formamidoimidazole-4-carboxamide ribotide sAMP, /V-succino-AMP. Enzymes (1) amido phosphoribosyltransferase (2) GAR synthetase (3) GAR transformylase (4) FGAM synthetase (5) AIR synthetase (6) AIR carboxylase (7) SAICAR synthetase (8) adenylosuecinase (9) AICAR transformylase (10) IMP cyclohydrolase (11) sAMP synthetase (12) adenylosuecinasc (13) IMP dehydrogenase (14) GMP synthetase.

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