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The kinetics of intramolecular distribution of 15N in uric acid after administration of (15N) glycine. A reappraisal of the significance of preferential labeling of N-(3+9) of uric acid in primary gout

The Journal of Clinical Investigation +

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October 1, 1973

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October 1, 1973

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Summary

This summary is machine-generated.

Gout patients with high uric acid production do not necessarily have abnormal glutamine metabolism. Instead, the observed isotopic enrichment is likely due to the rapid rate of purine biosynthesis itself.

Area Of Science

  • Biochemistry
  • Metabolic Disorders
  • Gout Pathophysiology

Background

  • Primary gout has been linked to abnormal glutamine metabolism based on isotope studies showing increased nitrogen-15 enrichment in uric acid.
  • This was attributed to a hypothetical defect in glutamine catabolism, leading to excess glutamine and uric acid overproduction.

Purpose Of The Study

  • To re-examine the proposed abnormality of glutamine metabolism in primary gout.
  • To investigate the driving force behind uric acid overproduction in different types of gout patients.

Main Methods

  • Administered nitrogen-15 labeled glycine to four gouty subjects with varying uric acid production levels.
  • Sampled precursor pools by administering benzoic acid (for glycine) and phenylacetic acid (for glutamine).
  • Analyzed isotopic enrichment in uric acid, hippuric acid, and phenylacetylglutamine.

Main Results

  • All gouty subjects showed disproportionately high labeling of N-(3+9) in uric acid, most pronounced in severe overproducers.
  • The time course of nitrogen-15 enrichment in glycine and glutamine pools differed, with glutamine enrichment being initially low.
  • Enrichment values in precursor pools (hippurate and phenylacetylglutamine) were normal in all subjects.
  • Greater enrichment of N-9 than N-3 suggested a potential second pathway for phosphoribosylamine synthesis.

Conclusions

  • The preferential enrichment of N-(3+9) in gouty overproducers is likely a kinetic phenomenon of accelerated purine biosynthesis, not a specific glutamine metabolism defect.
  • A potential second pathway for purine biosynthesis, possibly using ammonia, may exist but did not appear selectively increased in this study.

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