Molybdenum Cofactor Deficiency: Metabolic Link Between Taurine and S-Sulfocysteine
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.
KeywordsSulfite Oxidase Excretion Level Taurine Level Cysteine Sulfinic Acid Alkaline Picrate
Molybdenum cofactor deficiency
Sulfite oxidase deficiency
High-performance liquid chromatography
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).
- 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
- 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
- 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