Phosphoribosyl pyrophosphate amidotransferase (PPAT) (PPAT)

Phosphoribosyl pyrophosphate amidotransferase (PPAT) is the rate-limiting enzyme in the de novo purine biosynthesis pathway, responsible for converting 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine (UniProt P12235). This enzyme plays a critical role in maintaining the cellular nucleotide pool necessary for DNA and RNA synthesis, making it vital for cell growth and proliferation (PubMed: 35110554). Recent studies have identified PPAT as a direct target of metformin, a widely used anti-diabetic drug. Metformin binds to PPAT and inhibits its enzymatic activity, which leads to a reduction in purine levels and subsequent inhibition of cancer cell growth, particularly in non-small cell lung cancer (NSCLC) (Nature Communications, 2022). Beyond cancer, dysregulation of PPAT is associated with metabolic conditions like hyperuricemia and gout, where overactivity leads to excessive uric acid production (StatPearls). Consequently, PPAT is an emerging therapeutic target for both oncology and metabolic diseases.

Other names

AmidophosphoribosyltransferaseATaseGlutamine-PRPP amidotransferaseGPATPRPP amidotransferase

Metformin directly binds to and inhibits the enzymatic activity of PPAT, thereby suppressing de novo purine synthesis and inhibiting cell proliferation (PubMed: 35110554).