Studies on phospholipid biosynthesis in hepatocytes from alcoholic rats by using radiolabeled exogenous precursors.

We have studied the synthesis of phospholipids in hepatocytes isolated from chronically ethanol-treated rats by using isotopically labelled serine, ethanolamine, and choline as exogenous precursors. Our results demonstrate that ethanol induces specific effects on the biosynthesis of phosphatidylethanolamine and phosphatidylcholine via CDP-derivatives and also on the synthesis of phosphatidylserine via the Ca(++)-dependent base-exchange reaction. Thus, the synthesis of phosphatidylethanolamine from [3-H]ethanolamine and the incorporation of [3H]serine into phosphatidylserine were clearly higher in hepatocytes from ethanol-treated rats compared to controls. The synthesis of phosphatidylcholine from [methyl-14C]choline, on the other hand, decreased markedly, suggesting a specific inhibition of cholinephosphotransferase activity. We have also demonstrated that the phosphatidylcholine levels are markedly decreased in hepatocytes isolated from chronically ethanol-treated rats as a consequence of the lower phosphatidylcholine biosynthesis. The decrease in the incorporation of radioactivity from choline to betaine, which we also found, is interpreted as being the result of a higher use of betaine as methyl donor instead of methionine to maintain the hepatic S-adenosylmethionine levels in chronic alcoholism.