Methionine adenosyltransferase and S-adenosylmethionine in alcoholic liver disease.

Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the formation of the principal methyl donor S-adenosylmethionine (SAMe). Studies in the past decade have shown that SAMe is not only a methyl donor, but also a key metabolite that regulates hepatocyte growth, death and differentiation. Abnormalities in MAT and decreased SAMe levels occur in experimental animals and humans with alcoholic liver disease. Chronic hepatic SAMe deficiency can result in the spontaneous development of steatohepatitis and hepatocellular carcinoma. This paper reviews MAT genes and SAMe in relation to alcoholic liver disease and the molecular mechanisms by which SAMe regulates hepatocyte growth and apoptosis.