On the mechanism of overproduction of uric acid in patients with primary gout.

Abstract

In order to study the rate of generation of uric acid in man, Benedict, Roche, Yu, Bien, Gutman, and Stetten (5-7) administered relatively large doses of glycine-N15 orally to control and gouty subjects and measured the appearance of isotope in urinary uric acid. With this technique, they demonstrated overincorporation of isotope into uric acid only in gouty subjects excreting large quantities of uric acid in urine. Subsequently, however, excessive incorporation of tracer quantities of glycine-1-C14 into uric acid was demonstrated in all of seven subjects studied, regardless of the stage of severity of the disease or of the magnitude of urinary uric acid excretion (8). These results indicated that overproduction of uric acid from glycine and other small molecules was the fundamental defect responsible for hyperuricemia in primary gout. The characteristics of the curves of uric acid enrichment indicated that excessive biosynthesis of uric acid occurred in these gouty subjects without the intermediary intervention of nucleic acids (5, 7, 8). Since the mechanism of overproduction of uric acid in primary gout has not been defined in detail, it was decided to investigate the incorporation of glycine-1-C'4 into various urinary purine bases and to compare enrichment patterns with those of uric acid determined simultaneously. From such comparisons, information was sought regarding purine intermediates involved in normal and abnormal uric acid production. These studies have suggested two types of mechanism resulting in uric acid synthesis in man and have strengthened the present concepts (5, 7, 8-12) that over-