ON THE MECHANISM OF OVERPRODUCTION OF URIC ACID IN PATIENTS WITH PRIMARY GOUT1

Abstract

Procedures are described for isolation from the urine of hypoxanthine, xanthine, adenine, guanine, 7-methyl-guanine and 7-methyl-8-hydroxyguanine in crystalline form suitable for measurement of C14 content. These purine bases were isolated following administration of glycine-1-C14, to control subjects and to patients with primary gout or myeloid metaplasia. Specific activity values were compared with those of uric acid over variable periods of time in normal subjects and in patients with disorders of purine metabolism. Two major mechanisms exist by which uric acid is generated in man. In addition to catabolism of nucleic acids to yield purine bases subsequently converted to uric acid, nucleotide cleavage reactions ap-parently occur which yield highly labeled purine bases in urine within hours after the administration of glycine-1-C14. In normal and gouty subjects the synthesis of labeled uric acid from glycine-1-CH ap-parently occurs primarily via the "shunt" mechanism but in the patient with myeloid metaplasia, a second mechanism, presumably of augmented nucleic acid turnover, accounts for the late (second week) synthesis of considerable additional labeled uric acid. The patterns of labeling of urinary purines in patients with primary gout, and a comparison of these with the initial purine labeling pattern of a patient with myeloid metaplasia and generalized overproduction of nucleotides suggest that patients with primary gout may also have faulty regulation of rates of nucleotide synthesis, in which excessive purine nucleotide synthesis is followed by rapid conversion of surplus purine bases to uric acid. Several purine nucleotides may be involved in the derangement of purine metabolism of primary gout.