Advertisement

Taurine 8 pp 13-19 | Cite as

Molybdenum Cofactor Deficiency: Metabolic Link Between Taurine and S-Sulfocysteine

  • Abdel Ali BelaidiEmail author
  • Guenter Schwarz
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 776)

Abstract

Molybdenum cofactor deficiency (MoCD) is a rare inherited metabolic disorder characterized by severe and progressive neurologic damage mainly caused by the loss of sulfite oxidase activity. Elevated urinary levels of sulfite, thiosulfate, and S-sulfocysteine (SSC) are hallmarks in the diagnosis of both MoCD and sulfite oxidase deficiency. Sulfite is generated throughout the catabolism of sulfur-containing amino acids cysteine and methionine. Accumulated sulfite reacts with cystine, thus leading to the formation of SSC, a glutamate analogue, which is assumed to cause N-methyl-d-aspartate receptor-mediated neurodegeneration in MoCD patients. Recently, we described a fast and sensitive HPLC method for diagnostic and treatment monitoring of MoCD patients based on SSC quantification. In this study, we extend the HPLC method to the analysis of hypotaurine and taurine in urine samples and no interference with other compounds was found. Besides the known elevation of SSC and taurine, also hypotaurine shows strong accumulation in MoCD patients, for which the molecular basis is not understood. SSC, hypotaurine, and taurine urinary excretion values from control individuals as well as MoCD patients are reported and over 20-fold increase in taurine urinary excretion was determined for MoCD patients demonstrating a direct link between sulfite toxicity and taurine biosynthesis in MoCD.

Keywords

Sulfite Oxidase Excretion Level Taurine Level Cysteine Sulfinic Acid Alkaline Picrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

Moco

Molybdenum cofactor

MoCD

Molybdenum cofactor deficiency

SOD

Sulfite oxidase deficiency

SSC

S-sulfocysteine

HPLC

High-performance liquid chromatography

Notes

Acknowledgements

We thank Sita Arjune for helpful discussions and Simona Jansen for technical support. This work was funded by the Center for Molecular Medicine Cologne grant D5 (to GS).

References

  1. Belaidi AA, Arjune S, Santamaria-Araujo JA, Sass JO, Schwarz G (2011) Molybdenum Cofactor Deficiency: A New HPLC Method for Fast Quantification of S-Sulfocysteine in Urine and Serum. JIMD Reports. doi:101007/8904_2011_89Google Scholar
  2. El Idrissi A, Trenkner E (1999) Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. J Neurosci 19:9459–9468PubMedGoogle Scholar
  3. El Idrissi A, Trenkner E (2004) Taurine as a modulator of excitatory and inhibitory neurotransmission. Neurochem Res 29:189–197PubMedCrossRefGoogle Scholar
  4. Griffith OW (1987) Mammalian sulfur amino acid metabolism: an overview. Methods Enzymol 143:366–376PubMedCrossRefGoogle Scholar
  5. Johnson JL, Duran M (2001) Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. In: Scriver C et al (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3163–3177Google Scholar
  6. Johnson JL, Waud WR, Rajagopalan KV, Duran M, Beemer FA, Wadman SK (1980) Inborn errors of molybdenum metabolism: combined deficiencies of sulfite oxidase and xanthine dehydrogenase in a patient lacking the molybdenum cofactor. Proc Natl Acad Sci USA 77:3715–3719PubMedCrossRefGoogle Scholar
  7. Lee H-J, Adham IM, Schwarz G, Kneussel M, Sass J-O, Engel W, Reiss J (2002) Molybdenum cofactor-deficient mice resemble the phenotype of human patients. Hum Mol Gen 11:3309–3317PubMedCrossRefGoogle Scholar
  8. Olney JW, Misra CH, de Gubareff T (1975) Cysteine-S-sulfate: brain damaging metabolite in sulfite oxidase deficiency. J Neuropathol Exp Neurol 34:167–177PubMedCrossRefGoogle Scholar
  9. Sass JO, Nakanishi T, Sato T, Shimizu A (2004) New approaches towards laboratory diagnosis of isolated sulphite oxidase deficiency. Ann Clin Biochem 41:157–159PubMedCrossRefGoogle Scholar
  10. Schwarz G, Mendel RR, Ribbe MW (2009) Molybdenum cofactors, enzymes and pathways. Nature 460:839–847PubMedCrossRefGoogle Scholar
  11. Schwarz G, Santamaria-Araujo JA, Wolf S, Lee HJ, Adham IM, Grone HJ, Schwegler H, Sass JO, Otte T, Hanzelmann P, Mendel RR, Engel W, Reiss J (2004) Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli. Hum Mol Genet 13:1249–1255PubMedCrossRefGoogle Scholar
  12. Tan WH, Eichler FS, Hoda S, Lee MS, Baris H, Hanley CA, Grant PE, Krishnamoorthy KS, Shih VE (2005) Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature. Pediatrics 116:757–766PubMedCrossRefGoogle Scholar
  13. Veldman A, Santamaria-Araujo JA, Sollazzo S, Pitt J, Gianello R, Yaplito-Lee J, Wong F, Ramsden CA, Reiss J, Cook I, Fairweather J, Schwarz G (2010) Successful treatment of molybdenum cofactor deficiency type A with cPMP. Pediatrics 125:e1249–e1254PubMedCrossRefGoogle Scholar
  14. Zhang X, Vincent AS, Halliwell B, Wong KP (2004) A mechanism of sulfite neurotoxicity: direct inhibition of glutamate dehydrogenase. J Biol Chem 279:43035–43045PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Chemistry and Center for Molecular Medicine CologneInstitute of Biochemistry, University of CologneCologneGermany

Personalised recommendations