Phosphoribosyl aminoimidazole carboxylate

The fixation of COj or HCO3 into phosphoribosyl aminoimidazole led to the formation of a new intermediate because CO2 was knoivn to furnish the C-6 position, it was identified as phosphoribosyl aminoimidazole carboxylate. The reaction is readily reversible. 

The reaction of aspartate with phosphoribosyl aminoimidazole carboxylate produced a compound whose acidity indicated that the dicarboxylic... 

Aspartate is required for the subsequent metabolism of phosphoribosyl aminomidazole carboxylate, and phosphoribosyl aminoimidazole accumulates because of the ready reversibility of the carboxylation reaction. 

In this way, the nitrogen from several amino adds can be transferred to aspartate, glutamate or glutamine The ketoacid acceptors may originate from glucose or gluconeogenic precursors. The C-1 atom on formyltetrahydrofolate may arise from serine or methionine. In addition HC07 is required for the carboxylation of 5 -phosphoribosyl-5-aminoimidazole. 

As noted in Scheme 12.87, the early stages of purine biosynthesis involve the generation of 5-aminoimidazole ribotide [5-amino-2-(5 -phosphoribosyl)imidazole]. In vertebrates, carboxylation of 5-aminoimidazole ribotide (Scheme 12.96) is effected with carbon dioxide (CO2) under the influence of phosphoribosylaminoimidazole... 

Then as shown in Scheme 13.67 (a reproduction of Scheme 12.96), 5-aminoimidazole ribose 5-phosphate is carboxylated (either with CO2 or with bicarbonate) to 5-carboxyamino-l-(5 -phosphoribosyl)imidazole, which rearranges to 5-aminoimidazole ribotide-4-carboxylate, and the latter undergoes amination from aspartate (Asp, D) to yield 5-amino-l-(5-phosphoribosyl)imidazole-4-carboxamide after the loss of fumarate. Finally (Scheme 13.8), A-formylation is effected with lO-CHO-H, folate to yield the A-formyl derivative (5-formamido-l-(5 -phosphoribosyl)imidaz-ole-4-carboxyamide) and cyclization yields inosine 5 -phosphate (IMP). 

FIGURE 14. Structural comparison (from left to right) of Amitrole, 5 -phosphoribosyl-5-aminoimidazole-4-carboxylic acid, Virazole, and 2-amino-l,3,4-thiadiazole. 

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