Intramolecular distribution of uric acid-N15 after administration of glycine-N15 and ammonium-N15 chloride to goury and non-goury subjects.

Abstract

Thus far, administration of N'5- or C14-labeled uric acid precursors to patients with primary gout has revealed an unequivocal metabolic aberration (namely, grossly increased total uric acid-N'5 or -C14) only in some cases (3-8), estimated to represent roughly 30 per cent of the gouty population (9). This group of gouty subjects is further characterized by greatly enhanced uric acid excretion while maintaining enlarged uric acid pools-clear evidence of production of uric acid considerably in excess of the normal. In the remaining gouty subjects studied, apparently representative of the majority of cases of primary gout, the available isotope data either reveal lesser increases in utilization of isotope-labeled precursors for uric acid biosynthesis, manifest only when appropriate corrections are made for enlarged uric acid pools and increased uric acid excretion into the gut (10), or fail to disclose any distinct metabolic abnormality whatever. In the isotope studies made to date, measurements have been limited almost exclusively to total uric acid-N15 or -C14; i.e., the mean isotope enrichment of all four nitrogens or all five carbons, collectively, of the uric acid molecule. The present study extends such measurements to analysis of the intramolecular distribution of uric acid-N'5, and explores further the possibility of abnormal distribution of isotope within the uric acid molecule even when the total uric acid isotope abundance approximates that found in nongouty subjects. Dissection of the uric acid molecule in this way can be particularly revealing in gout now that the sequential enzymatic reactions effecting placement of each atom in purine biosynthesis are securely established (11).