Erythrocyte PRPP Concentrations in Heterozygotes for HGPRTase Deficiency
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 de novo. Hershko et al (1) found increased in vitro 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. However, other workers (2, 3) failed to find elevated PRPP levels in erythrocytes of patients with gout who had normal hypoxanthineguanine phosphoribosyltransferase (HGPRTase) activity in their erythrocytes. On the other hand, patients with either severe or moderate degrees of deficiency of the enzyme HGPRTase regularly demonstrated elevated erythrocyte PRPP concentrations. It was suggested (2) that in HGPRTase deficient subjects, the elevated erythrocyte PRPP levels reflected the cells diminished utilization of this compound by the HGPRTase catalysed reaction.
KeywordsErythrocyte Lysate Purine Biosynthesis Moderate Deficiency Adenine Phosphoribosyltransferases Serum Urate Concentration
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- 2.GREENE, M.L. and SEEGMILLER, J.E. (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.Google Scholar
- 3.FOX, I.H. and KELLEY, W.N. (1971). Phosphoribosylpyrophosphate in man: Biochemical and clinical significance. Ann. Intern. Med. 71: 424–433.Google Scholar
- 4.EMERSON, B.T., THOMPSON, C.J. and WALLACE, D.C. (1972). Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase: Intermediate enzyme deficiency in heterozygote red cells. Ann. Intern. Med. 76: 285–287.Google Scholar
- 5.SPERLING, O., EILAM, G., PERSKY-BROSH, S. and DEVRIES, A. (1972). Simpler method for the determination of 5-phosphoribosyl-1-pyrophosphate in red blood cells. J. Lab. Clin. Med. 79: 1021–1026.Google Scholar
- 9.SPERLING, O., BOER, P., PERSKY-BROSH, S., KANAREK, E. and Devries, A. (1972). Altered kinetic property of erythrocyte phosphoribosylpyrophosphate synthetase in excessive purine production. Rev. Eur. Etud. Clin. Biol. 17: 24.Google Scholar
- 10.BECKER, M.A., MEYER, L.J., WOOD, A.W. and SEEGMILLER, J.E. (1972). Gout associated with increased PRPP synthetase activity. Meeting of the American Rheumatism Association, Abstract No. 8.Google Scholar