Taurine Deficiency and MELAS Are Closely Related Syndromes - Advances in Experimental Medicine and Biology - page 144

The major pathway of taurine biosynthesis involves the oxidation of cysteine
to cysteine sulfinic acid, the decarboxylation of cysteine sulfinic acid to hypotau-
rine, and the oxidation of hypotaurine to taurine (Jacobsen and Smith 1968 ) . The
amount of taurine generated by this hepatic pathway depends upon the activity of
the rate-limiting enzyme, cysteine sulfinic acid decarboxylase, whose activity is
nonexistent in cats, low in humans, and high in rodents (Bagley and Stipanuk
1995 ; Gaull 1986 ; Jacobsen and Smith 1968 ). Thus, cats can be nutritionally
depleted of taurine but a taurine-deficient state can only be achieved in rodents by
either inhibiting or knocking out the taurine transporter, which supplies extrahe-
patic cells with taurine from nutritional and biosynthetic sources. In the present
review, the primary symptoms of MELAS (in humans) and taurine deficiency (in
nutritionally depleted cats, taurine transporter knockout mice, and taurine trans-
porter-inhibited rats) are compared.

16.2 Link Between MELAS Syndrome and Taurine De fi ciency

16.2.1 Cardiovascular Defects of MELAS and Taurine

De fi ciency

Comorbidity of MELAS and cardiac disease is relatively common (Anan et al.
1995 ). This is not surprising because the heart requires high rates of ATP biosyn-
thesis for the maintenance of normal contractile function. Interestingly, both
hypertrophic and dilated cardiomyopathies have been observed in patients suf-
fering from MELAS, suggesting that the pathophysiology of the mitochondrial
disease is complex and may involve multiple factors. In fact, MELAS is also
associated with conduction defects, including a high incidence of Wolff-
Parkinson-White syndrome.
A cardiomyopathy and conductance defects are common in taurine-deficient
animals. The taurine-deficient cardiomyopathy in cats exhibits both diastolic and
systolic dysfunction (Novotny et al. 1991, 1994 ) although the majority of cats
presenting with taurine-deficient cardiomyopathy suffer from only systolic dys-
function. Pion et al. ( 1987, 1992 ) found that cats with taurine deficiency-mediated
dilated cardiomyopathy are successfully treated with taurine (Pion et al. 1987,
1992 ). However, prior to the discovery of taurine's role in the disease, many cats
died with signs of cardiogenic shock and congestive heart failure (Pion et al.
1992 ). Although there are no reports of taurine deficiency causing Wolff-
Parkinson-White-like syndrome, taurine depletion leads to prolongation of the
action potential and the QT interval, which also increase the risk of arrhythmias
(Lake et al. 1987 ). Thus, there are numerous similarities between the cardiovas-
cular defects of taurine deficiency and MELAS. The possibility that taurine ther-
apy might benefit MELAS, as it does congestive heart failure, is worthy of
consideration (Azuma et al. 1983 ) .