Purine Nucleotide Synthesis

The cell's ability to provide the needed purine nucleotides for DNA and RNA synthesis is also critical to its survival. The de novo biosynthesis of purine nucleotides involves 10 separate enzyme catalyzed reactions starting with 5-phosphoribosyl-1-pyrophosphate and leading to inosinic acid.11 Both adenosine monophosphate (AMP) and guanine monophosphate are then derived from inosinic acid (Figure 2). The third step in this process is the biosynthesis of formylglycinamide ribonucleotide from glycinamide ribonucleotide (GR) via glycinamide ribonucleotide formyltransferase (GARFT). The last two steps in the synthesis of inosinic acid occur via a bifunctional enzyme having both aminoimidazolecarboxamide ribonucleotide formyltransferase (AICARFT) and inosine monophosphate cyclohydrolase (IMPCH) activity. This enzyme is composed of a 39 kDa C-terminal AICARFT active fragment along with a 25 kDa N-terminal IMPCH active fragment.12 Both GARFT and AICARFT catalyze the transfer of a formyl group from 10-CHO-tetrahydrofolate (10-CHO-THF) to GR or aminoimidazolecarboxamide ribonucleotide (AICAR) respectively, returning THF as the second product of the reaction.

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