Molecular variation in relation to purine metabolism.

The disorders of purine metabolism illustrate the causation of human disease by molecular variants in the sense of different abnormal enzymes producing the same clinico-pathological manifestations and of different inherited anomalies of the same enzyme protein resulting in the same clinical manifestations. Except for the clinical recognition of tophaceous gout and uric acid urinary stones, an abnormal concentration of uric acid in the blood or urine is the usual indicator of an abnormality in this area of metabolism, and the serum uric acid is usually measured in routine biochemical profiles. The methods of measuring uric acid in biological fluids were recently reviewed by Watts (1974a). Those based on the reduction of phosphotungstate or arsenophosphotungstate solutions are liable to interference by other reducing agents, and these errors are particularly important in the analysis of urine. Methods depending on the high specificity of the uricase (urate: oxygen oxidoreductase EC 1.7.3.3) catalyzed oxidation of uric acid are preferred.