Overproduction of Uric Acid as the Cause of Hyperuricemia in Primary Gout

Abstract

The rate of generation of uric acid in gouty subjects was re-investigated by feeding tracer doses of glycine-1-C14 and determining the excretion of C14 in urinary uric acid. Six subjects had histories of acute gouty arthritis, and one had asymptomatic hyperuricemia. Two gouty subjects excreted excessive quantities of urate, whereas the other 4 and the asymptomatic hyperuricemic subject excreted quantities within the normal range. All 7 gouty subjects exhibited excessive incorporation of C14 into urinary urate. Degradation of the labeled urate suggested that glycine was incorporated intact and indicated negligible non-specific labeling of the purine nucleus by secondary reactions. These results constitute strong evidence that overproduction of uric acid from glycine and other small molecules is the fundamental defect responsible for the hyperuricemia of primary gout. The characteristics of the curves of C14 incorporation into uric acid strongly suggest, as did earlier studies with glycine-N15, that nucleic acids are not involved in the overproduction of uric acid in primary gout.