Human Phosphoribosylpyrophosphate (PP-ribose-P) Synthetase: Properties and Regulation

Abstract

PP-ribose-P and the enzyme catalyzing its synthesis, PP-riboseP synthetase, were initially discovered by Kornberg, Lieberman and Simms in 1955. PP-ribose-P was subsequently recognized to be an essential substrate for purine, pyridine and pyrimidine biosynthesis, as well as for the formation of other compounds. Recent studies on the control of PP-ribose-P synthesis in bacteria, Ehrlich tumor ascites cells and human erythrocytes have suggested a complicated system of control depending upon ribose-5-P availability, cell energy levels and feedback inhibition from end products. Additional observations have suggested that the intracellular concentration of PP-ribose-P has a critical regulatory role in the biosynthesis of purines de novo in man. In order to clarify the regulation of PP-ribose-P synthesis, we have purified and studied this enzyme from human erythrocytes.