We have determined the effect of prolonged ethanol treatment on several enzyme activities related to lipid metabolism in chick-brain and liver microsomes. Ethanol incrcascd microsome cho!esterol levels in both organs. The treatment caused a marked increase in the hepatic HMG-CoA rcductase and ACAT activities while in the brain a clear decrease was found in these enzyme activities. At the same time the aaivity of reacylation of phospholipids. was clearly mcdificd in both brain and liver. Thus, while in the liver the turnover ofacyl moieties of phosphatidylethanolamine, sphingomyelin and phosphatidylinositol was enhanced by ethanol consumption. in the brain only the reacylation of phosphatidylserine increased to any significant extent. These results indicate that ethanol exerts a differential action in brain and liver, namely cholesterol synthesis and esterification decreased in brain and increased in chick liver. Ethanol also induces faster phospholipid metabolism in both brain and liver microsomes.

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.

1 The aim of the present study was to investigate the effects of ethanol in vitro on the phospholipid biosynthetic pathways in hepatocytes isolated from the rat. We have used [methyl-"4C] products of the CDP-choline and CDP-ethanolamine pathways. Radioactivity in the metabolic intermediates of both pathways was significantly decreased and the amount of label in PE was reduced whilst that of PC was not modified. 3 In the presence of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase (ADH) activity, ethanol produces a reduction in the label of choline phosphate, ethanolamine phosphate and a significant decrease in the amount of PC and PE radiolabel. 4 On the other hand, ethanol increases the incorporation of serine into phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine, although this effect is observed only in the absence of 4-methylpyrazole, indicating that this alteration is produced by some metabolite generated as a consequence of hepatic alcohol metabolism. 5 Ethanol also interferes with the methylation of phosphatidylethanolamine produced via the CDPethanolamine pathway but it does not alter phosphatidylethanolamine methylation when this phospholipid is produced by mitochondrial phosphatidylserine decarboxylation, suggesting the existence of different intramembrane pools of phosphatidylethanolamine, which may exhibit different sensitivity to alcohol. 6 Our results indicate that ethanol exerts two different effects on phospholipid metabolism in hepatocytes: a stimulatory effect on the incorporation of exogenous substrates into different phospholipids probably related to an alteration in the availability of lipogenic substrates as a consequence of ethanol metabolism, and another inhibitory effect produced by ethanol per se, which can be observed only when ethanol metabolism is inhibited by the presence of a specific inhibitor of alcohol dehydrogenase activity.

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