S-adenosyl-L-methionine: Role in phosphatidylcholine synthesis and in vitro effects on the ethanol-induced alterations of lipid metabolism

Hepatic lipid metabolism is extremely modified by excessive ethanol consumption, but the cellular mechanisms of such alterations are still largely unexplored. S-Adenosyl-L-methionine (SAMe) is known as an important methylating agent and as a precursor of glutathione and it has been shown to prevent some of the toxic effects of ethanol in the liver. We therefore studied the effects of ethanol on cholesterol synthesis in a human hepatomal cell line (HepG2), the kinetics of SAMe, and its putative protective effects on the alterations of lipid metabolism induced by toxic concentrations of alcohol. Incubation of HepG2 cells with [H-3]SAMe resulted in a progressive increase in the labelling of phosphatidylcholine and of its two intermediates during synthesis starting from phosphatidylethanolamine. This process is enzymatic, since it does not take place in heat-inactivated cells. Also, ethanol induced an increase in cholesterol and triglycerides syntheses and a decrease in phospholipid labelling. These alterations were not prevented by SAMe 10(-4) M, indicating that the protective effects of the drug are related to other mechanisms of action such as reduced formation of collagen, restoration of glutathione levels, and normalization of membrane functions. (C) 1998 The Italian Pharmacological Society.