Biology Reference
In-Depth Information
Chapter 2
Molybdenum Cofactor De fi ciency: Metabolic
Link Between Taurine and S-Sulfocysteine
Abdel Ali Belaidi and Guenter Schwarz
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 de fi ciency. Sul fi te 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 treat-
ment 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 uri-
nary 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.
Abbreviations
Moco
Molybdenum cofactor
MoCD
Molybdenum cofactor de fi ciency
SOD
Sul fi te oxidase de fi ciency
A. A. Belaidi (
*
) G. Schwarz
Department of Chemistry and Center for Molecular Medicine Cologne,
Institute of Biochemistry, University of Cologne , Cologne , Germany
e-mail: belaidia@uni-koeln.de
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