Cell type-specific differential expression of human PRPP synthetase (PRPS) genes.

Abstract

PRPP is a substrate in the synthesis of virtually all nucleotides1 and is also an important regulator of the de novo pathways of purine2 and pyrimidine 3 nucleotide synthesis. PRPP is synthesized from MgATP and Rib-5-P in a reaction requiring Mg2+ and Pi as activators and subject to inhibition by purine, pyrimidine, and pyridine nucleotides; reaction products; and 2,3-diphosphoglycerate 4-6 . The reaction is catalyzed by a family of PRPP synthetase (PRS) isoforms . Mammalian PRS isoform subunits are polypeptides of about 35 kDa, with a high degree of homology both within and across species . Purified human PRS subunits, whether recombinant or isolated from cells, undergo concentration-dependent and effector-mediated reversible aggregation in vitro, 4,10 with enzymatic activity residing in aggregates containing as many as 16 or 32 subunits. Active heteroaggregates of PRS have not been formally demonstrated, but each human recombinant PRS isoform forms active homoaggregates 4,7 . The human PRS isoform family is composed of 3 polypeptides of identical length. Each human PRS cDNA is encoded by a separate PRPS gene: human PRPS1 and PRPS2 map, respectively, to the long and the short arms of the X chromosome and are widely expressed; PRPS3 maps to human chromosome 7