Protective roles of transsulfuration against methionine toxicity

Methionine is an essential amino acid in mammals, but is the most toxic among the constituent amino acids of proteins. Excessive methionine intake causes oxidative/nitrosative injuries in the liver, hepatic/splenic hypertrophy, altered erythrocyte morphology, and the resultant splenic hemosiderosis in rats; however, the pathophysiology of methionine-induced liver toxicity remains to be elucidated. Methionine can be metabolized into cysteine by methionine cycle and transsulfuration, and cysteine can be further metabolized into cytoprotective metabolites such as glutathione, taurine, and hydrogen sulfide (H2S). We recently found that a methionine-rich diet induces acute lethal hepatitis in transsulfuration-defective cystathionine γ-lyase-deficient mice. Molecular mechanisms by which methionine excess induces hepatic dysfunction and physiological roles of transsulfuration in its detoxification (metabolism) are herein reviewed.