Molybdenum Cofactor Deficiency: Metabolic Link Between Taurine and S-Sulfocysteine - Advances in Experimental Medicine and Biology - page 16

to control individuals. The fact that not only taurine but also hypotaurine, the direct
precursor for taurine synthesis, are excreted in high levels in urine of MoCD patients
provides evidence for an up-regulation of the entire taurine biosynthesis pathway
from CSA via hypotaurine to taurine. Thus, an exclusive contribution of taurine
transport is not the sole explanation. As a 64-fold increase in SSC levels was mea-
sured in MoCD patients, while only a 20-fold increase in both hypotaurine and
taurine was found, we assume that sulfite-mediated SSC formation precedes the
accumulation of taurine and hypotaurine, pointing to a more distal metabolic rela-
tionship. In summary, it remains unclear how sulfite and/or SSC contributes to this
up-regulation. Due to the previously reported important role of taurine in preventing
neurotoxicity (El Idrissi and Trenkner 1999 ), we speculate that taurine up-regula-
tion may result from a compensatory effect to overcome the toxicity caused by SSC
in the brain or a feedback inhibition of the sulfite branch in cysteine catabolism, thus
leading to an increased taurine formation. Additional experiments are required to
elucidate the effect of taurine, especially on the SSC-induced neurotoxicity.

2.5 Conclusion

Here we confirm the link between MoCD and taurine biosynthesis using a novel
method for the simultaneous detection of SSC, taurine, and hypotaurine in healthy
control individuals and MoCD patients. Interestingly, the analysis of urine samples
derived from MoCD patients revealed over 20-fold increase in both hypotaurine and
taurine levels as compared to control individuals, thus providing evidence for an up-
regulation of the hypotaurine and taurine pathway and demonstrating a link between
sulfite toxicity and taurine biosynthesis in MoCD patients. However, it remains
unclear by which mechanisms taurine and hypotaurine are up-regulated in MoCD.

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).

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