The first purine product of this pathway, IMP (inosinic acid or inosine monophosphate), serves as a precursor to AMP and GMP. Step 1: PRPP synthesis from ribose-5-phosphate and ATP by ribose-5-phosphate pyrophosphokinase. Step 2: 5-Phosphoribosyl-b-1-amine synthesis from a-PRPP, glutamine, and H2O by glutamine phosphoribosyl pyrophosphate amidotransferase. Step 3: Glycinamide ribonucleotide (GAR) synthesis from glycine, ATP, and 5-phosphoribosyl-b-amine by glycinamide ribonucleotide synthetase. Step 4: Formylglycinamide ribonucleotide synthesis from N10-formyl-THF and GAR by GAR transformylase. Step 5: Formylglycinamidine ribonucleotide (FGAM) synthesis from FGAR, ATP, glutamine, and H2O by FGAM synthetase (FGAR amidotransferase). The other products are ADP, Pi, and glutamate. Step 6: 5-Aminoimidazole ribonucleotide (AIR) synthesis is achieved via the ATP-dependent closure of the imidazole ring, as catalyzed by FGAM cyclase (AIR synthetase). (Note that the ring closure changes the numbering system.) Step 7: Carboxyaminoimidazole ribonucleotide (CAIR) synthesis from CO2, ATP, and AIR by AIR carboxylase. Step 8: N-succinylo-5-aminoimidazole-4-carboxamide ribonucleotide (SAICAR) synthesis from aspartate, CAIR, and ATP by SAICAR synthetase. Step 9: 5-Aminoimidazole carboxamide ribonucleotide (AICAR) formation by the nonhydrolytic removal of fumarate from SAICAR. The enzyme is adenylosuccinase. Step 10: 5-Formylaminoimidazole carboxamide ribonucleotide (FAICAR) formation from AICAR and N10-formyl-THF by AICAR transformylase. Step 11: Dehydration/ring closure yields the authentic purine ribonucleotide IMP. The enzyme is IMP synthase.
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