Phosphoribosylpyrophosphate amidotransferase (PPAT) (PPAT)

Phosphoribosylpyrophosphate amidotransferase (PPAT) is the rate-limiting enzyme responsible for the first committed step in the de novo purine biosynthetic pathway (UniProt: P12259). It catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) and glutamine into 5-phosphoribosyl-1-amine, a precursor for inosine monophosphate (IMP) (NCBI Gene: 5471). This enzyme is critical for maintaining the cellular pool of purine nucleotides required for DNA and RNA synthesis, especially in rapidly dividing cells (StatPearls: Purine Metabolism). In many cancers, such as lung and liver cancer, PPAT is significantly upregulated to support increased metabolic demands, making it a potential target for antineoplastic therapy (PMID: 28655770). Dysregulation of PPAT activity is also linked to metabolic disorders such as gout and hyperuricemia due to the overproduction of uric acid (Wikipedia: Amidophosphoribosyltransferase). Pharmacologically, PPAT is targeted by purine antimetabolites like 6-mercaptopurine, which are metabolized into analogs that exert allosteric feedback inhibition on the enzyme (PubChem: CID 667490). Inhibition of PPAT leads to the depletion of essential nucleotides, resulting in the suppression of cell proliferation and induction of apoptosis.

Other names

AmidophosphoribosyltransferaseGlutamine phosphoribosylpyrophosphate amidotransferaseGPATPRPPAT

Allosteric feedback inhibition of the rate-limiting step in de novo purine synthesis by nucleotide analogs (PubChem: CID 667490).