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Current concepts in the pathogenesis of hyperuricemia

1973; Elsevier BV; Volume: 22; Issue: 7 Linguagem: Inglês

10.1016/0026-0495(73)90066-8

1532-8600

William N. Kelley, Wolfgang Gröbner, Edward W. Holmes,

Porphyrin Metabolism and Disorders

In recent years a number of specific concepts have been developed regarding the regulation of purine biosynthesis in man. At the present time, the most important factors involved in the control of this pathway appear to be the intracellular concentration of 5-phosphoribosyl-1-pyrophosphate (PP-ribose-P) and purine nucleotides. In addition, a number of enzymatic abnormalities, which may lead to an accelerated rate of purine biosynthesis de novo and hyperuricemia, have now been described. These include a deficiency of hypoxanthine-guanine phosphoribosyltransferase, a deficiency of glucose-6-phosphatase, increased activity of phosphoribosylpyrophosphate synthetase, increased activity of glutathione reductase, and increased activity of xanthine oxidase. Each of these enzymatic abnormalities may increase the production of purines by altering the intracellular concentration of PP-ribose-P or purine nucleotides. In addition, an abnormal form of P-ribose-P amidotransferase, which may increase purine biosynthesis by virtue of a reduced sensitivty to the normal inhibitory effect of purine nucleotides, has been described. Abnormalities in the renal handling of uric acid are relatively common causes of hyperuricemia. However, at the present time, the molecular basis for these abnormalities remains to be defined.