Human Phosphoribosylpyrophosphate (PRPP) Synthetase Requirements for Subunit Aggregation

Abstract

The high energy sugar phosphate 5-phosphoribosyl 1-pyrophosphate (PRPP) is synthesized from MgATP and ribose-5-phosphate in a reaction catalyzed by PRPP synthetase (E.C. 2.7.6.1). In vitro studies of this enzyme,^1–6 as well as evaluations of PRPP production in intact cells, 7,8 indicate that PRPP synthetase activity is regulated in a complex fashion involving the interaction of substrates, activators, reaction products and diverse inhibitors. Enzyme activity is strictly dependent upon the presence of inorganic phosphate (Pi) and Mg²⁺ which serve both as activators and cofactors.³ Among inhibitors of PRPP synthetase activity are purine, pyrimidine and pyridine nucleotide end-products of the pathways of PRPP utilization, the reaction products (PRPP and AMP), and 2,3-DPG.^3,6