Inosine monophosphate (de novo purine synthesis)

Route: 5-Phosphoribosyl 1-pyrophosphate → 5-Phosphoribosylamine + Glycine → Glycinamide ribonucleotide → Formylglycinamide ribonucleotide → Formylglycinamidine ribonucleotide → 5-Aminoimidazole ribonucleotide → Carboxyaminoimidazole ribonucleotide + Aspartate → SAICAR → AICAR → FAICAR → Inosine monophosphate

Glycine, glutamine, aspartate, formate (carried as 10-formyl-THF) and CO₂ supply every atom of the purine ring. The ring is never built free; it grows on the ribose phosphate from PRPP, so the product is already a nucleotide. In humans three enzymes each do several steps: the trifunctional GART carries out steps 2, 3 and 5 (GARS, GART and AIRS domains), PAICS carries out steps 6 and 7, and ATIC carries out steps 9 and 10. The structures shown are of the domains named in each step. The structure of the ring-closing AIRS domain shown here is of the stand-alone bacterial enzyme. Steps 2, 4, 5 and 7 each use one ATP. The pathway runs at a high rate in dividing cells, and antifolate cancer drugs such as pemetrexed block the folate-dependent steps. The product IMP is the branch point to AMP and GMP.

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Steps

Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).