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. 1980 Jun;77(6):3715–3719. doi: 10.1073/pnas.77.6.3715

Inborn errors of molybdenum metabolism: combined deficiencies of sulfite oxidase and xanthine dehydrogenase in a patient lacking the molybdenum cofactor.

J L Johnson, W R Waud, K V Rajagopalan, M Duran, F A Beemer, S K Wadman
PMCID: PMC349689  PMID: 6997882

Abstract

A patient suffering from a combined deficiency of sulfite oxidase (sulfite dehydrogenase; sulfite:ferricytochrome c oxidoreductase, EC 1.8.2.1) and xanthine dehydrogenase (xanthine:NAD+ oxidoreductase, EC 1.2.1.37) is described. The patient displays severe neurological abnormalities, dislocated ocular lenses, and mental retardation. Urinary excretion of sulfite, thiosulfate, S-sulfocysteine, taurine, hypoxanthine, and xanthine is increased in this individual, while sulfate and urate levels are drastically reduced. The metabolic defect responsible for loss of both enzyme activities appears to be at the level of the molybdenum cofactor common to the two enzymes. Immunological examination of a biopsy sample of liver tissue revealed the presence of the xanthine dehydrogenase protein in near normal amounts. Sulfite oxidase apoprotein was not detected by a variety of immunological techniques. The plasma molybdenum concentration was normal; however, hepatic content of molybdenum and the storage pool of active molybdenum cofactor present in normal livers were below the limits of detection. Fibroblasts cultured from this patient failed to express sulfite oxidase protein or activity, whereas those from the parents and healthy brother of the patient expressed normal levels of this enzyme.

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Selected References

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

  1. Amy N. K., Rajagopalan K. V. Characterization of molybdenum cofactor from Escherichia coli. J Bacteriol. 1979 Oct;140(1):114–124. doi: 10.1128/jb.140.1.114-124.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BEAUFAY H., BENDALL D. S., BAUDHUIN P., DE DUVE C. Tissue fractionation studies. 12. Intracellular distribution of some dehydrogenases, alkaline deoxyribonuclease and iron in rat-liver tissue. Biochem J. 1959 Dec;73:623–628. doi: 10.1042/bj0730623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chuang H. Y., Patek D. R., Hellerman L. Mitochondrial monoamine oxidase. Inactivation by pargyline. Adduct formation. J Biol Chem. 1974 Apr 25;249(8):2381–2384. [PubMed] [Google Scholar]
  4. Johns D. G. Human liver aldehyde oxidase: differential inhibition of oxidation of charged and uncharged substrates. J Clin Invest. 1967 Sep;46(9):1492–1505. doi: 10.1172/JCI105641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Johnson J. L., Cohen H. J., Rajagopalan K. V. Molecular basis of the biological function of molybdenum. Molybdenum-free sulfite oxidase from livers of tungsten-treated rats. J Biol Chem. 1974 Aug 25;249(16):5046–5055. [PubMed] [Google Scholar]
  6. Johnson J. L., Hainline B. E., Rajagopalan K. V. Characterization of the molybdenum cofactor of sulfite oxidase, xanthine, oxidase, and nitrate reductase. Identification of a pteridine as a structural component. J Biol Chem. 1980 Mar 10;255(5):1783–1786. [PubMed] [Google Scholar]
  7. Johnson J. L., Jones H. P., Rajagopalan K. V. In vitro reconstitution of demolybdosulfite oxidase by a molybdenum cofactor from rat liver and other sources. J Biol Chem. 1977 Jul 25;252(14):4994–5003. [PubMed] [Google Scholar]
  8. Johnson J. L., Rajagopalan K. V., Cohen H. J. Molecular basis of the biological function of molybdenum. Effect of tungsten on xanthine oxidase and sulfite oxidase in the rat. J Biol Chem. 1974 Feb 10;249(3):859–866. [PubMed] [Google Scholar]
  9. Johnson J. L., Rajagopalan K. V. Human sulfite oxidase deficiency. Characterization of the molecular defect in a multicomponent system. J Clin Invest. 1976 Sep;58(3):551–556. doi: 10.1172/JCI108500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Johnson J. L., Rajagopalan K. V. Tryptic cleavage of rat liver sulfite oxidase. Isolation and characterization of molybdenum and heme domains. J Biol Chem. 1977 Mar 25;252(6):2017–2025. [PubMed] [Google Scholar]
  11. Johnson J. L., Waud W. R., Cohen H. J., Rajagopalan K. V. Molecular basis of the biological function of molybdenum. Molybdenum-free xanthine oxidase from livers of tungsten-treated rats. J Biol Chem. 1974 Aug 25;249(16):5056–5061. [PubMed] [Google Scholar]
  12. KAUFMAN S. THE STRUCTURE OF THE PHENYLALANINE-HYDROXYLATION COFACTOR. Proc Natl Acad Sci U S A. 1963 Dec;50:1085–1093. doi: 10.1073/pnas.50.6.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Krenitsky T. A., Neil S. M., Elion G. B., Hitchings G. H. A comparison of the specificities of xanthine oxidase and aldehyde oxidase. Arch Biochem Biophys. 1972 Jun;150(2):585–599. doi: 10.1016/0003-9861(72)90078-1. [DOI] [PubMed] [Google Scholar]
  14. Lewis N. J., Scazzocchio C. The genetic control of molybdoflavoproteins in Aspergillus nidulans. A xanthine dehydrogenase I half-molecule in cnx- mutant strains of Aspergillus nidulans. Eur J Biochem. 1977 Jun 15;76(2):441–446. doi: 10.1111/j.1432-1033.1977.tb11613.x. [DOI] [PubMed] [Google Scholar]
  15. MILLER E., HLAD C. J., Jr, LEVINE S., HOLMES J. H., ELRICK H. USE OF RADIOISOTOPES TO MEASURE BODY FLUID CONSTITUENTS. II. URINE SULFATE. J Lab Clin Med. 1963 Oct;62:710–714. [PubMed] [Google Scholar]
  16. McCord J. M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049–6055. [PubMed] [Google Scholar]
  17. Mudd S. H., Levy H. L., Abeles R. H., Jennedy J. P., Jr A derangement in B 12 metabolism leading to homocystinemia, cystathioninemia and methylmalonic aciduria. Biochem Biophys Res Commun. 1969 Apr 10;35(1):121–126. doi: 10.1016/0006-291x(69)90491-4. [DOI] [PubMed] [Google Scholar]
  18. Nason A., Antoine A. D., Ketchum P. A., Frazier W. A., 3rd, Lee D. K. Formation of assimilatory nitrate reductase by in vitro inter-cistronic complementation in Neurospora crassa. Proc Natl Acad Sci U S A. 1970 Jan;65(1):137–144. doi: 10.1073/pnas.65.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Niederwieser A., Matasović A., Steinmann B., Baerlocher K., Kempken B. Hydantoin-5-propionic aciduria in folic acid nondependent formiminoglutamic aciduria observed in two siblings. Pediatr Res. 1976 Apr;10(4):215–219. doi: 10.1203/00006450-197604000-00002. [DOI] [PubMed] [Google Scholar]
  20. PATEMAN J. A., COVE D. J., REVER B. M., ROBERTS D. B. A COMMON CO-FACTOR FOR NITRATE REDUCTASE AND XANTHINE DEHYDROGENASE WHICH ALSO REGULATES THE SYNTHESIS OF NITRATE REDUCTASE. Nature. 1964 Jan 4;201:58–60. doi: 10.1038/201058a0. [DOI] [PubMed] [Google Scholar]
  21. Payes B., Greenberg D. M. Studies on the enzymic decomposition of urocanic acid. VII. Identification of the enzyme catalyzing the oxidation of 4(5)-imidazolone-5(4)-propionic acid as an aldehyde oxidase. Arch Biochem Biophys. 1968 Jun;125(3):911–917. doi: 10.1016/0003-9861(68)90530-4. [DOI] [PubMed] [Google Scholar]
  22. Pienkos P. T., Shah V. K., Brill W. J. Molybdenum cofactors from molybdoenzymes and in vitro reconstitution of nitrogenase and nitrate reductase. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5468–5471. doi: 10.1073/pnas.74.12.5468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. SORBO B. A colorimetric method for the determination of thiosulfate. Biochim Biophys Acta. 1957 Feb;23(2):412–416. doi: 10.1016/0006-3002(57)90346-3. [DOI] [PubMed] [Google Scholar]
  24. Shah V. K., Brill W. J. Isolation of an iron-molybdenum cofactor from nitrogenase. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3249–3253. doi: 10.1073/pnas.74.8.3249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shih V. E., Abroms I. F., Johnson J. L., Carney M., Mandell R., Robb R. M., Cloherty J. P., Rajagopalan K. V. Sulfite oxidase deficiency. Biochemical and clinical investigations of a hereditary metabolic disorder in sulfur metabolism. N Engl J Med. 1977 Nov 10;297(19):1022–1028. doi: 10.1056/NEJM197711102971902. [DOI] [PubMed] [Google Scholar]
  26. Stoop J. W., Zegers B. J., Hendrickx G. F., van Heukelom L. H., Staal G. E., de Bree P. K., Wadman S. K., Ballieux R. E. Purine nucleoside phosphorylase deficiency associated with selective cellular immunodeficiency. N Engl J Med. 1977 Mar 24;296(12):651–655. doi: 10.1056/NEJM197703242961203. [DOI] [PubMed] [Google Scholar]
  27. Willard H. F., Mellman I. S., Rosenberg L. E. Genetic complementation among inherited deficiencies of methylmalonyl-CoA mutase activity: evidence for a new class of human cobalamin mutant. Am J Hum Genet. 1978 Jan;30(1):1–13. [PMC free article] [PubMed] [Google Scholar]
  28. van Gennip A. H., van Noordenburg-Huistra D. Y., de Bree P. K., Wadman S. K. Two-dimensional thin-layer chromatography for the screening of disorders of purine and pyrimidine metabolism. Clin Chim Acta. 1978 May 16;86(1):7–20. doi: 10.1016/0009-8981(78)90452-7. [DOI] [PubMed] [Google Scholar]

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