Molybdenum Cofactor Deficiency: Metabolic Link Between Taurine and S-Sulfocysteine - Advances in Experimental Medicine and Biology - page 15

Fig. 2.2 Hypotaurine, taurine, and SSC urinary levels in control individuals and MoCD patients.
Urine samples derived from control individuals and nine MoCD patients are shown in panel ( a )
and ( b ), respectively. In addition, numbers over the bars in panel ( b ) indicate the fold increase in
the median value in MoCD patients for each metabolite. Metabolites in urine were normalized to
creatinine concentration and horizontal bars show the median values

(180-600 mmol/mol creatinine, Fig. 2.2b ), very high levels of both hypotaurine and
taurine. The excretion levels of taurine were in the millimolar range and reached
over 25-fold increase in the median value of healthy individuals, while a 21-fold
increase in the median value of hypotaurine was found (Fig. 2.2b ).

2.4 Discussion

MoCD is a rare metabolic disorder characterized by a severe and massive neurode-
generation leading to death in early childhood. SSC which is present at very low
levels in healthy individuals (Johnson and Duran 2001 ; Belaidi et al. 2011 ) is one of
the most elevated metabolites in MoCD patients and due to its structural similarity
to glutamate, it is believed to act on NMDA receptors (Olney et al. 1975 ) . In the
past, many reports showed an important role of taurine in modulating glutamate and
GABA signaling (El Idrissi and Trenkner 1999, 2004 ) . Furthermore, taurine has
been shown to prevent excitotoxicity through modulation of intracellular calcium
homeostasis (El Idrissi and Trenkner 1999 ). Knowing the importance of calcium
signaling in the glutamate-induced neurotoxicity and the fact that taurine and sulfite
are both formed directly from CSA, we asked to which extent taurine is also affected
in MoCD. We developed an HPLC method for the simultaneous detection of SSC,
hypotaurine, and taurine in urine samples aiming to determine the excretion levels
of those compounds in control and MoCD patients. Our results showed over 20-fold
higher excretion values for hypotaurine and taurine in MoCD patients as compared