Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Mar;79(3):847–852. doi: 10.1172/JCI112893

Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

F A Mateos, J G Puig, M L Jiménez, I H Fox
PMCID: PMC424217  PMID: 3818951

Abstract

We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 10(6) cpm/g creatinine in both patients and to 4.73 +/- 0.69 X 10(6) cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398 +/- 86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 microM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria.

Full text

PDF
847

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AYVAZIAN J. H., SKUPP S. THE STUDY OF PURINE UTILIZATION AND EXCRETION IN A XANTHINURIC MAN. J Clin Invest. 1965 Jul;44:1248–1260. doi: 10.1172/JCI105231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bode J. C., Zelder O., Rumpelt H. J., Wittkamp U. Depletion of liver adenosine phosphates and metabolic effects of intravenous infusion of fructose or sorbitol in man and in the rat. Eur J Clin Invest. 1973 Sep;3(5):436–441. doi: 10.1111/j.1365-2362.1973.tb02211.x. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. J., Krakoff I. H., Leeper R., Balis M. E. Study of purine metabolism in a xanthinuric female. J Clin Invest. 1968 Jun;47(6):1325–1332. doi: 10.1172/JCI105824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CASKEY C. T., ASHTON D. M., WYNGAARDEN J. B. THE ENZYMOLOGY OF FEEDBACK INHIBITION OF GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE AMIDOTRANSFERASE BY PURINE RIBONUCLEOTIDES. J Biol Chem. 1964 Aug;239:2570–2579. [PubMed] [Google Scholar]
  5. Dwosh I. L., Roncari D. A., Marliss E., Fox I. H. Hypouricemia in disease: a study of different mechanisms. J Lab Clin Med. 1977 Jul;90(1):153–161. [PubMed] [Google Scholar]
  6. ENGELMAN K., WATTS R. W., KLINENBERG J. R., SJOERDSMA A., SEEGMILLER J. E. CLINICAL, PHYSIOLOGICAL AND BIOCHEMICAL STUDIES OF A PATIENT WITH XANTHINURIA AND PHEOCHROMOCYTOMA. Am J Med. 1964 Dec;37:839–861. doi: 10.1016/0002-9343(64)90128-7. [DOI] [PubMed] [Google Scholar]
  7. Edwards N. L., Recker D., Airozo D., Fox I. H. Enhanced purine salvage during allopurinol therapy: an important pharmacologic property in humans. J Lab Clin Med. 1981 Nov;98(5):673–683. [PubMed] [Google Scholar]
  8. Edwards N. L., Recker D., Fox I. H. Overproduction of uric acid in hypoxanthine-guanine phosphoribosyltransferase deficiency. Contribution by impaired purine salvage. J Clin Invest. 1979 May;63(5):922–930. doi: 10.1172/JCI109392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fox I. H. Adenosine triphosphate degradation in specific disease. J Lab Clin Med. 1985 Aug;106(2):101–110. [PubMed] [Google Scholar]
  10. Fox I. H., Kelley W. N. Studies on the mechanism of fructose-induced hyperuricemia in man. Metabolism. 1972 Aug;21(8):713–721. doi: 10.1016/0026-0495(72)90120-5. [DOI] [PubMed] [Google Scholar]
  11. Fox I. H. Metabolic basis for disorders of purine nucleotide degradation. Metabolism. 1981 Jun;30(6):616–634. doi: 10.1016/0026-0495(81)90142-6. [DOI] [PubMed] [Google Scholar]
  12. Fox I. H., Wyngaarden J. B., Kelley W. N. Depletion of erythrocyte phosphoribosylpyrophosphate in man. N Engl J Med. 1970 Nov 26;283(22):1177–1182. doi: 10.1056/NEJM197011262832201. [DOI] [PubMed] [Google Scholar]
  13. Gehrke C. W., Kuo K. C., Davis G. E., Suits R. D., Waalkes T. P., Borek E. Quantitative high-performance liquid chromatography of nucleosides in biological materials. J Chromatogr. 1978 Mar 21;150(2):455–476. doi: 10.1016/s0021-9673(00)88205-9. [DOI] [PubMed] [Google Scholar]
  14. Hartwick R. A., Brown P. R. Evaluation of microparticle chemically bonded reversed-phase packings in the high-pressure liquid chromatographic analysis of nucleosides and their bases. J Chromatogr. 1976 Nov 3;126:679–691. doi: 10.1016/s0021-9673(01)84111-x. [DOI] [PubMed] [Google Scholar]
  15. Holmes E. W., Jr, Mason D. H., Jr, Goldstein L. I., Blount R. E., Jr, Kelley W. N. Xanthine oxidase deficiency: studies of a previously unreported case. Clin Chem. 1974 Aug;20(8):1076–1079. [PubMed] [Google Scholar]
  16. Kageyama N. A direct colorimetric determination of uric acid in serum and urine with uricase-catalase system. Clin Chim Acta. 1971 Feb;31(2):421–426. doi: 10.1016/0009-8981(71)90413-x. [DOI] [PubMed] [Google Scholar]
  17. Kelley W. N., Greene M. L., Rosenbloom F. M., Henderson J. F., Seegmiller J. E. Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann Intern Med. 1969 Jan;70(1):155–206. doi: 10.7326/0003-4819-70-1-155. [DOI] [PubMed] [Google Scholar]
  18. Kelley W. N., Rosenbloom F. M., Henderson J. F., Seegmiller J. E. A specific enzyme defect in gout associated with overproduction of uric acid. Proc Natl Acad Sci U S A. 1967 Jun;57(6):1735–1739. doi: 10.1073/pnas.57.6.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kelley W. N., Rosenbloom F. M., Miller J., Seegmiller J. E. An enzymatic basis for variation in response to allopurinol. Hypoxanthine-guanine phosphoribosyltransferase deficiency. N Engl J Med. 1968 Feb 8;278(6):287–293. doi: 10.1056/NEJM196802082780601. [DOI] [PubMed] [Google Scholar]
  20. Kelley W. N., Wyngaarden J. B. Effects of allopurinol and oxipurinol on purine synthesis in cultured human cells. J Clin Invest. 1970 Mar;49(3):602–609. doi: 10.1172/JCI106271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kojima T., Nishina T., Kitamura M., Hosoya T., Nishioka K. Biochemical studies on the purine metabolism of four cases with hereditary xanthinuria. Clin Chim Acta. 1984 Feb 28;137(2):189–198. doi: 10.1016/0009-8981(84)90179-7. [DOI] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Phillips M. I., Davies D. R. The mechanism of guanosine triphosphate depletion in the liver after a fructose load. The role of fructokinase. Biochem J. 1985 Jun 15;228(3):667–671. doi: 10.1042/bj2280667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Puig J. G., Fox I. H. Ethanol-induced activation of adenine nucleotide turnover. Evidence for a role of acetate. J Clin Invest. 1984 Sep;74(3):936–941. doi: 10.1172/JCI111512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rundles R. W., Metz E. N., Silberman H. R. Allopurinol in the treatment of gout. Ann Intern Med. 1966 Feb;64(2):229–258. doi: 10.7326/0003-4819-64-2-229. [DOI] [PubMed] [Google Scholar]
  26. Salti I. S., Kattuah N., Alam S., Wehby V., Frayha R. The effect of allopurinol on oxypurine excretion in xanthinuria. J Rheumatol. 1976 Jun;3(2):201–204. [PubMed] [Google Scholar]
  27. Simmonds H. A., Levin B., Cameron J. S. Variations in allopurinol metabolism by xanthinuric subjects. Clin Sci Mol Med. 1974 Aug;47(2):173–178. doi: 10.1042/cs0470173. [DOI] [PubMed] [Google Scholar]
  28. Simmonds H. A. Urinary excretion of purines, pyrimidines and pyrazolopyrimidines in patients treated with allopurinol or oxipurinol. Clin Chim Acta. 1969 Feb;23(2):353–364. doi: 10.1016/0009-8981(69)90052-7. [DOI] [PubMed] [Google Scholar]
  29. Sutton J. R., Toews C. J., Ward G. R., Fox I. H. Purine metabolism during strenuous muscular exercise in man. Metabolism. 1980 Mar;29(3):254–260. doi: 10.1016/0026-0495(80)90067-0. [DOI] [PubMed] [Google Scholar]
  30. Vincent M. F., Van den Berghe G., Hers H. G. Effect of fructose on the concentration of phosphoribosylpyrophosphate in isolated hepatocytes. Adv Exp Med Biol. 1986;195(Pt B):615–621. doi: 10.1007/978-1-4684-1248-2_96. [DOI] [PubMed] [Google Scholar]
  31. YUE T. F., GUTMAN A. B. EFFECT OF ALLOPURINOL (4-HYDROXYPYRAZOLO-(3,4-D)PYRIMIDINE) ON SERUM AND URINARY URIC ACID IN PRIMARY AND SECONDARY GOUT. Am J Med. 1964 Dec;37:885–898. doi: 10.1016/0002-9343(64)90131-7. [DOI] [PubMed] [Google Scholar]
  32. Zakaria M., Brown P. R. Investigation of clinical methodology for sample collection and processing prior to the reversed-phase liquid chromatographic determination of UV-absorbing plasma constituents. Anal Biochem. 1982 Feb;120(1):25–37. doi: 10.1016/0003-2697(82)90313-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES