Taurine Deficiency and MELAS Are Closely Related Syndromes - Advances in Experimental Medicine and Biology - page 150

2006 ; Roysommuti et al. 2009 ). However, there is no evidence that taurine deficiency
is associated with the development of global glomerulosclerosis although one would
predict that the loss of its antioxidant and anti-inflammatory activities may render
the kidney susceptible to glomerulosclerosis. According to Trachtman et al. ( 1992 ) ,
taurine treatment has been shown to decrease the degree of renal injury in chronic
puromycin aminonucleoside proteinuric renal disease, which is a model of focal
segmental glomerulosclerosis.

16.3 Conclusions

16.3.1 Are the MELAS Symptoms and Taurine De fi ciency

Defects Identical?

The MELAS syndrome and taurine deficiency are remarkably similar. Both conditions
lead to cardiomyopathies, metabolic abnormalities, growth failure, hearing defects,
muscle weakness and exercise intolerance, retinopathies, and renal defects. These
findings suggest that the pathophysiology of the two conditions is probably similar.
Although there is no experimental evidence that taurine deficiency leads to reduced
levels of 5-taurinomethyluridine-tRNA Leu(UUR) , there is evidence that taurine serves as
the substrate for the posttranslational modification of the wobble uridine base (unpub-
lished data). There is also evidence that taurine deficiency, like deficiency of
5-taurinomethyluridine-tRNA Leu(UUR) , leads to impaired UUG decoding, decreased
respiratory chain activity, enhanced oxidative stress, and stimulation of anaerobic
metabolism (Jong et al. 2012 ; Mozaffari et al. 1986 ). Because the generation of ATP
and the regulation of superoxide production are basic functions required for mainte-
nance and viability of all cells, it is not surprising that taurine deficiency and MELAS
affect the function of virtually all organ systems. The observation that the effects of
taurine deficiency are so biochemically similar to the pathophysiology of MELAS
unconditionally links the two conditions.

16.3.2 Unique Taurine-De fi cient Actions

Historically, taurine serves as a neuromodulator, regulator of the immune system,
membrane stabilizer, osmoregulator, and modulator of cation transport (Huxtable
1992 ). These effects are unrelated to MELAS because they do not involve changes
in 5-taurinomethyluridine-tRNA Leu(UUR) levels. Rather, these effects involve a dis-
tinct conjugation reaction (formation of taurine chloramine), a change in protein or
enzyme activity (membrane stabilization, neuromodulation), an alteration in tissue
osmolyte load (osmoregulation, cation transport modulation), or a change in cation
transport (via taurine transporter). Although the regulation of mitochondrial reactive