Human Phosphoribosylpyrophosphate Synthetase (PRS) 2: An Independent Active, X Chromosone-Linked PRS Isoform

Cloning of rodent and human (h)phosphoribosylpyrophosphate synthetase (PRS) cDNAs has resulted in identification of multiple PRS transcripts,1–3 at least two of which are encoded by separate X chromosome-linked genes (PRPS1 and PRPS2) in man.4,5 The normal hPRPS1 gene product, hPRS1, has been studied in detail in enzyme preparations purified from erythrocytes.6–9 In two unrelated patients in whom PRS superactivity is accompanied by purine nucleotide feedback-resistance, gout with uric acid overproduction, and neurodevelopmental impairment, single base substitutions in hPRS1 cDNA which predict changes in hPRS1 primary structure have recently been identified.10 Although PRS2 (as well as PRS1) transcripts are present in RNA preparations from all organs thus far tested,2 little is known about the role or regulation of hPRS2 activity. We have applied molecular genetic, cytogenetic, and biochemical methods to study the hPRPS2 gene and the corresponding hPRS2 cDNA, RNA transcript, and protein.