Evidence of differential effects produced by ethanol on specific phospholipid biosynthetic pathways in rat hepatocytes

Abstract

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.

Hexadecylphosphocholine inhibits phosphatidylcholine synthesis via both the methylation of phosphatidylethanolamine and CDP-choline pathways in HepG2 cells

“…In the light of these findings, our previous experience with hepatic cells and research into the action of different xenobiotics on phospholipid metabolism [17,18] has prompted us to investigate the effect of HePC on the tumoral hepatic cell line HepG2. We studied its cytotoxic and cytostatic activity against HepG2 cells and examined its influence on de novo PC biosynthesis by using the precursor [methyl-14 C]choline as radioactive marker.…”

Hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis and the proliferation of HepG2 cells

“…In the light of these findings, our previous experience with hepatic cells and research into the action of different xenobiotics on phospholipid metabolism [17,18] has prompted us to investigate the effect of HePC on the tumoral hepatic cell line HepG2. We studied its cytotoxic and cytostatic activity against HepG2 cells and examined its influence on de novo PC biosynthesis by using the precursor [methyl‐ 14 C]choline as radioactive marker.…”

Metabolic Fate of [¹⁴C]-Ethanol into Endothelial Cell Phospholipids Including Platelet-Activating Factor, Sphingomyelin and Phosphatidylethanol

“…The formation of the phospholipid phosphatidylethanol (PEth) during ethanol exposure has been implicated in the pathogenesis of alcohol-induced organ damage [7]. Hepatic triacylglycerol accumulations have been described in chronic alcoholism [12]; however, reports on the effects of ethanol administration on the biosynthesis of cellular phospholipids are few and contradictory [4,10,16]. Several researchers have found that ethanol affects the incorporation and distribution of various exogenously supplied substrates in different ways.…”