S-ADENOSYLMETHIONINE IN HEPATOCYTE GROWTH, APOPTOSIS CANCER

摘要

S-adenosylmethionine (SAMe, also known as AdoMet and SAM) was discovered more than half a century ago as a methyl donor, but in recent years its role in hepatocyte growth, death, differentiation, injury, and neoplastic transformation has received increasing notice. In the US SAMe is widely used as a health supplement, but in Europe it is used therapeutically in cholestatic and alcoholic liver diseases. SAMe synthesis occurs in all mammalian cells in a reaction catalyzed by the essential enzyme methionine adenosyltransferase (MAT). SAMe is particularly important in the liver as most forms of chronic liver injury result in reduced SAMe biosynthesis due to decreased hepatic MAT activity. Chronic hepatic SAMe deficiency occurs in MAT1A knockout mice andleads to livers that are more susceptible to injury, development of steatohepatitis, and hepatocellular carcinoma (HCC). This session reviews hepatic SAMe metabolism, regulation of MAT genes and isoenzymes, consequences of chronic hepatic SAMe deficiency, and SAMe's effect on hepatocytes growth and apoptosis. New insights regarding how SAMe exerts its hepatoprotective action are provided and its potential role as a chemopreventive agent against HCC are being proposed.