Purine Synthesis

Step 1

Production of PRPP: Ribose-5-phosphate (from the Pentose Phosphate Pathway) is converted to 5-phosphoribosyl-1-pyrophosphate (PRPP) by PRPP Synthetase, which has kinase activity and adds pyrophosphate. Not a committed step — PRPP is also used for histidine biosynthesis and pyrimidine synthesis.

Step 2

Production of Phosphoribosylamine: PRPP reacts with glutamine via glutamine-PRPP amidotransferase. This is the rate-limiting, committed step, regulated allosterically by IMP, AMP, and GMP (inhibitors). Forms the glycosidic bond.

Step 3

Production of IMP: 11 reactions build the purine ring onto the amine group, drawing atoms from glycine, aspartate, glutamine, CO₂, and N¹⁰-formyl-THF (two formyl groups). Nitrogen comes from four sources: glutamine (×2), aspartate, and glycine.

Step 4

Branching to AMP or GMP: IMP branches to either adenylosuccinate → AMP (requires GTP and aspartate; inhibited by AMP) or xanthylate (XMP) → GMP (requires ATP and glutamine; inhibited by GMP).