Radioimmunoassay studies of human phosphoribosylpyrophosphate synthetase.

Abstract

5-Phosphoribosyl 1-pyrophosphate (PRPP), an intermediate in the synthesis of purine, pyrimidine and pyridine nucleotides, is synthesized from ATP and ribose-5-P in a magnesium- and inorganic phosphate-requiring reaction catalyzed by PRPP synthetase. Activity of PRPP synthetase is subject to inhibition by a variety of small molecule effectors including reaction products, purine and pyrimidine nucleo — tides, and 2,3-diphosphoglycerate.1,2 Human PRPP synthetase is composed of a single polypeptide subunit3 the structural gene for which maps to the long arm of the X-chromosome,4 The PRPP synthetase sub-unit is capable of reversible self-association3,5 to forms containing 2,4,8,16 and 32 subunits, only the largest two of which contain significant enzyme activity.6 Aggregation and disaggregation of PRPP synthetase subunits are concentration-dependent and effect-mediated processes6 which may in part underlie the regulation of intracellular PRPP synthesis.