Title: Purine metabolism in man, II
Description: The study of gouty arthritis has provided a common meeting ground for the research interests of both the basic scientist and the clinician. The interest of the chemist in gout began 1776 with the isolation of uric acid from a concretion of the urinary tract by the Swedish chemist SCHEELE. The same substance was subsequently extracted from a gouty tophus by the British chemist WOLLASTONE in 1797 and a half century later the cause of the deposits of sodium urate in such tophi was traced to a hyperuricemia in the serum of gouty patients by the British physician Alfred Baring GARROD who had also received training in the chemical laboratory and was therefore a fore-runner of many of today's clinician-investigators. The recent surge of progress in understanding of some of the causes of gout in terms of specific enzyme defects marks the entrance of the biochemist into this field of investigation.

The identification of the first primary defect of purine metabolism associated with over-production of uric acid, a severe or partial deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase was achieved less than a decade ago. The knowledge of the mechanism of purine over-production that it generated led shortly to the identification of families carrying a dominantly (possibly X-linked) inherited increase in the activity of the enzyme phosphoribosylpyrophosphate synthetase as a cause of purine over-production. Yet this is only a start as these two types of enzyme defects account for less than five per cent of gouty patients. The rapid pace at which new knowledge of aberrations of human purine metabolism is being acquired is adequate reason for holding the Second International Symposium on Purine Metabolism in Man (Baden, Austria, June 20 - 26, 1976) just three years after the first symposium was convened.

It also marks the bicentennial anniversary of the discovery of uric acid by SCHEELE. The table of contents shows a further consolidation of our understanding of the mechanisms involved in the synthesis and degradation of purines and the aberrations produced in regulation of these processes by well characterized defects in purine metabolism. In addition are reports of newly discovered defects in enzymes of purine metabolism not previously presented at the last symposium. Homozygousity for deficiency of adenine phosphoribosyltransferase has now been identified in three children, two of whom presented with calculi of the urinary tract composed of 2,8-dihydroxyadenine thus setting at rest previous speculations based on studies of heterozygotes for this disorder. On the basis of recent experiments the understanding of renal handling of urate has been further increased indicating a pre- and post-secretory reabsorption.

The significance of protein-binding of urate is still open for discussion. However the knowledge of mechanisms regulating purine transport through membranes has improved by development of rapid micromethods. A whole new area of considerable importance for the future is the association of an impaired function of the immune system in children with a gross deficiency of either of two sequential enzymes of purine interconversion, adenosine deaminase or purine nucleoside phosphorylase. Further investigation of the mechanism of this phenomenon gives promise of extending substantially our knowledge of the normal control of the immune response.
Subjects: Gout, Metabolisme, Lipid Metabolism, Metabolisme, maladies hereditaires du, Inborn errors of Metabolism, Uric acid, Glucides, Enzymology, Congresses, Purines, Lipides, Carbohydrate Metabolism, Metabolism, Urique, acide, Purine-Pyrimidine Metabolism, Inborn Errors, Errors, Carbohydrates, Lipids, Purine-pyrimidine metabolism, Inborn