Phosphoribosyl pyrophosphate synthetase 1 (PRPS1)

Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is a ubiquitously expressed enzyme responsible for catalyzing the transfer of pyrophosphate from ATP to ribose-5-phosphate, producing phosphoribosyl pyrophosphate (PRPP), an essential precursor for purine and pyrimidine nucleotide de novo synthesis and salvage pathways. PRPS1 activity is tightly regulated by allosteric modulators and post-translational modifications, notably phosphorylation. Mutations that enhance or impair PRPS1 enzymatic function are implicated in diverse diseases: hyperactivity causes metabolic syndromes (gout, hyperuricemia), while loss-of-function leads to neurodegenerative disorders. PRPS1's phosphorylation state, especially at serine 103, is emerging as a biomarker for colorectal cancer progression and may guide precision oncology. Recent studies show PRPS1 forms filamentous assemblies, providing an additional layer of allosteric control over metabolic flux

Other names

Ribose-phosphate pyrophosphokinase 1PRPS1PRS-ICMTX5DFNX1PPRibPPhosphoribosyl pyrophosphate synthase Iribose-phosphate diphosphokinase 1ARTSDFN2dJ1070B1.2 (phosphoribosyl pyrophosphate synthetase 1)PRSIdeafness 2, perceptive, congenitalCharcot-Marie-Tooth disease X-linked (CMTX5)Arts syndrome

Not fully established pharmacologically. For disease modulation, strategies may involve inhibition of PRPS1 phosphorylation (particularly S103), which decreases enzyme activity and restricts cell cycle progression Targeting allosteric regulation (ADP, GDP inhibition; phosphate activation) Indirect mechanisms: kinase inhibitors targeting upstream regulators