A kinetic model for the intramolecular distribution of 15 N in uric acid in patients with primary gout fed 15 N-glycine

Published

Journal Article

The concept of an abnormality of glutamine metabolism in primary gout was first proposed on the basis of isotope data: when 15N-glycine was administered to gouty subjects, there was disproportionately great enrichment of N-(3+9) of uric acid, which derive from the amide-N of glutamine. An unduly high concentration of 15N in glutamine was postulated, and attributed to a hypothetical defect in the catabolism of glutamine. Excess glutamine was proposed as the driving force of uric acid overproduction. We have reexamined this proposition in four gouty and three control subjects. In three of the gouty subjects the driving force of excessive purine biosynthesis was a known surplus of α-5-phosphoribosyl-1-pyrophosphate. The precursor glycine and glutamine pools were sampled by isolation of urinary hippurate and phenylacetylglutamine. Enrichment values of hippurate and of phenacetylglutamine were normal in all of the gouty subjects studied. However, the time course of 15N enrichment of hippurate differed from that of the amide-N of glutamine. A kenetic model was constructed, and experimentally derived data were used to drive the model. It was found that disproportionate labeling of N-(3+9) could be produced from the model when appropriate constraints were used. Thus, preferential enrichment of N-(3+9) in gouty overproducers given 15N-glycine does not necessarily reflect a specific abnormality of glutamine metabolism, but rather appears to be a kinetic phenomenon associated with accelerated purine biosynthesis per se. © 1975.

Full Text

Duke Authors

Cited Authors

  • Frank Starmer, C; Sperling, O; Wyngaarden, JB

Published Date

  • January 1, 1975

Published In

Volume / Issue

  • 25 / 1-2

Start / End Page

  • 105 - 123

International Standard Serial Number (ISSN)

  • 0025-5564

Digital Object Identifier (DOI)

  • 10.1016/0025-5564(75)90055-3

Citation Source

  • Scopus