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-derivativ es and also on the synthesis of phosphatidylserine via the Ca++-depend ent base-exchange reaction. Thus, the synthesis of phosphatidylethanol amine from [(3)-H]ethanolamine and the incorporation of [H-3]serine in to phosphatidylserine were clearly higher in hepatocytes from ethanol- treated rats compared to controls. The synthesis of phosphatidylcholin e from [methyl-C-14]choline, on the other hand, decreased markedly, su ggesting a specific inhibition of cholinephosphotransferase activity. We have also demonstrated that the phosphatidylcholine levels are mark edly decreased in hepatocytes isolated from chronically ethanol-treate d rats as a consequence of the lower phosphatidylcholine biosynthesis. ,The decrease in the incorporation of radioactivity from choline to be taine, which we also found, is interpreted as being the result of a hi gher use of betaine as methyl donor instead of methionine to maintain the hepatic S-adenosylmethionine levels in chronic alcoholism.