Phosphoribosyl glycineamide

Phosphoribosyl glycineamide + 5,10-methenyl H -folate Phosphoribosyl aminoimidazole carboxamide -+ 10-formyl Hi-folate... 

Another reaction of purine biosynthesis de novo bears a resemblance to these reactions the synthesis of the amide, phosphoribosyl glycineamide. This is also listed in Table 5-IV, together with two closely related reactions, the synthesis of glutamine and of glutathione. 

Ribosylamine phosphate Phosphoribosyl glycineamide Phosphoribosyl formylglycineamide... 

Phosphoribosyl Glycineamide Synthesis The reaction by which phosphoribosyl glycineamide is synthesized is... 

Purine biosynthesis de novo was one of the hrst areas of metabolism in which a folic acid derivative was specifically identified as a cofactor in an enzymatic reaction. The ability of pigeon liver extracts to add formate to phosphoribosyl glycineamide was impaired by treatment with charcoal, but was restored by addition of H4-folate. Although the complicated interconversions of the Hrfolate coenzymes (see Chapter 5) caused confusion for some time, the specific one-carbon donor for this reaction was eventually identified as 5,10-methenyl H4-folate. The phosphoribosyl glycineamide formyltransferase reaction itself is irreversible. 

Phosphoribosyl glycineamide synthetase Carbon-nitrogen Amide synthesis Yes Yes... 

Phosphoribosyl glycineamide formyltransferase Carbon-nitrogen One-carbon transfer No No... 

Phosphoribosyl-AT-formyl-glycineamide tetrahydro-folate 5,10-formyl transferase Phosphoribosyl glycineamide formyltransferase... 

The antagonism of bactericidal sulfanilamides by p-aminobenzoic acid (PABA), a precursor of the vitamin folic acid, has been well documented in the pharmacological literature. More recently, it was shown that the phytotoxic activity of asulam, a herbicidal sulfanilamide derivative, also results from an inhibition of the biosynthesis of the vitamin folic acid. " In particular, asulam inhibits competitively the enzyme 7,8-dihydropteroate synthase, which catalyzes the conversion of 2-amino-4-hydroxy-6-hydroxy-methyl-7,8-dihydropteridine and PABA to dihydropteroic acid, leading to folate depletion. A consequence of the depletion of folic acid derivatives is the buildup of intermediates of the de novo synthesis of purine nucleo-tides. ° Such intermediates include 5 -phosphoribosyl glycineamide (GAR) or 5 -phosphoribosyl-5-amino-4-imidazole (AICAR). The accumulation of GAR and AICAR in asulam-treated pea seedlings has been reported. 

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.

S -Phosphoribosyl-formyl-glycineamide L-glutamine amido-ligase (ADP) Phosphoribosyl formyl-glycinearoidine synthetase... 

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