Regulation of Purine Biosynthesis De Novo

Abstract

Hyperuricemia can result from an increase in the rate of purine biosynthesis de novo, a decrease in the renal clearance of uric acid, or a combination of these two processes. The relative contribution of each of these processes to the development of hyperuricemia varies with the subpopulation under study. This might be expected, since gout is a clinical disorder of diverse etiologies. Some referral centers have reported that as many as 75% of their patients with gout exhibit increased rates of purine biosynthesis as judged from isotopic incorporation techniques (Gutman et al., 1958; Seegmiller et al., 1961). However, the experience in other centers suggests that only 15–25% of their patients with primary gout develop hyperuricemia due to an increase in the rate of purine biosynthesis (Watts et al., 1976). While the prevalence of purine overproduction in the general gouty population is not known, it appears that a significant proportion of these patients develop hyperuricemia due to an increase in the rate of purine biosynthesis de novo. Because of this association, the mechanisms responsible for the regulation of purine biosynthesis have been the subject of numerous studies.