Phosphoribosylpyrophosphate regulation

Wingaarden, J.B. Ashton, D.H. (1959). The regulation of activity of phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides a potential feedback control of purine biosynthesis. ]. Biol. Chem., 234, 1492-6. 

Wyngaarden, J. B. 1972. Glutamine phosphoribosylpyrophosphate amidotransferase. In Current Topics in Cellular Regulation. 

Greene, M. L., and J. E. Seegmiller. 1969. Elevated erythrocyte phosphoribosylpyrophosphate in X-linked uric aciduria Importance of PRPP concentration in the regulation of human purine biosynthesis. J. Clin. Invest. 48 32a. 

Phosphoribosylpyrophosphate (PRPP) synthetase (E.C. 2.7.6.1) catalyzes the formation of PRPP from ribose-5-phosphate and ATP in the presence of Mg and inorganic phosphate. The product, PRPP, is a substrate of the first rate limiting step of the de novo synthesis of purine nucleotides and its availability has been shown to regulate this pathway in human tissue (l). A superactive mutant erythrocyte PRPP synthetase with decreased sensitivity to feedback inhibition has recently been found by us in a gouty family (2,3). 

A specific localization of the control mechanism has been found. The enzyme, phosphoribosylpyrophosphate amidotransferase (44S) was inhibited by various purine ribonucleotides ATP and ADP were the most inhibitory (449). The regulation of enzyme activity by purine ribonucleotides offers a controlling mechanism for purine biosynthesis by maintaining a relatively constant amount of nucleotide within the cell. 

HUMAN GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE (PP-RIBOSE-P) AMIDOTRANS-FERASE KINETIC, REGULATION AND CONFIGURATIONAL CHANGES... 

Nagy, M. 1970. Regulation of the biosynthesis of purine nucleotides in Schizosaccharomyces pombe. I. Properties of the phosphoribosylpyrophosphate glutamine amidotransferase of the wild strain and of a mutant desensitized towards feedback modifers. Biochim. Biophys. Acta. 198 471-481. 

Nierlich, D.P. and Magasanik, B. 1965. Regulation of purine ribonucleotide synthesis by end product inhibition The effect of adenine and guanine ribonucleotides on the 5 -phosphoribosylpyrophosphate amidotransferase in Aerobacter aerogenes. J. 

In the last few years, phosphoribosylpyrophosphate (PRPP) has been viewed as a most important intermediate metabolite and studies have indicated that its concentration and rate of synthesis may play a critical role in the regulation of purine biosynthesis da novo. Hershko et al (l) found increased in vitvo formation of PRPP in the erythrocytes of some gouty subjects. They further suggested that the increase in the rate of purine uptake found in these patients was attributable to enhanced PRPP formation. 

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