Impairment of Methionine Metabolism in Liver Disease

Abstract

Methionine metabolism is impaired in patients with liver damage and this alteration might complicate and maintain the clinical syndrome. Alterations in this pathway are associated with a defect in S-adenosyl-L-methionine (SAMe) synthetase activity. Liver glutathione, which is derived from SAMe via the transsulphuration pathway, is also depleted as a result of liver damage. Glutathione appears to protect against SAMe synthetase inactivation by preventing oxidation of sulfhydryl groups; thus, its depletion further reduces SAMe synthetase activity, and a vicious circle may develop. Restoration of glutathione levels by the addition of treatment with SAMe or glutathione esters in various experimental conditions (buthionine sulfoximine and carbon tetrachloride intoxication) has resulted in attenuation of the damage produced by the toxins. Moreover, exogenously administered SAMe has been used successfully in patients with liver disease. The elucidation of the mechanisms that regulate methionine metabolism might lead to the development of new therapeutic approaches in liver disease.