DIFFERENTIAL IN-VITRO EFFECTS OF ETHANOL ON GLYCEROLIPID ACYLATION AND BIOSYNTHESIS IN RAT RETICULOCYTES

Earlier reports have shown that, in human and rat red blood cells (RBC ), ethanol modulates acylation reactions in several membrane glyceroli pid components. Little is known, however, about the kinetics and the m echanisms involved in the acylation changes. In the present study, we show that short-term in vitro exposure of intact rat reticulocytes to ethanol differentially modifies within minutes the incorporation of [H -3]oleic acid in glycerolipids. A concentration-dependent inhibition o f acyl incorporation was measured in phosphatidylcholine (PC) and phos phatidylethanolamine (PE). This effect did not involve inhibition of t he corresponding acyltransferase activities and is likely to be due to ethanol-dependent decreases in phospholipase activities. In contrast, ethanol markedly stimulated [H-3]oleic acid incorporation in phosphat idic acid (PA), diacylglycerol (DG) and, to a lesser extent, in triacy lglycerol (TG). To determine the mechanisms of the latter increases, r eticulocytes were pulsed with [C-14]glycerol and assayed as a function of time for labeled biosynthetic precursors and products. We observed a very close correlation between time courses and amplitudes of the e thanol stimulation of acylation and biosynthesis reactions, suggesting that stimulation of acylation in PA, DG and TG is causally related at least partly to their increased biosynthesis. Further studies reveale d that increases in glycerolipid acylation and biosynthesis in reticul ocytes were: (a) readily reversible upon ethanol withdrawal; (b) detec table for clinically relevant concentration (50 mM) of ethanol; and (c ) associated with concomitant increases in cell resistance to hemolysi s. These changes may be relevant to the development of tolerance to et hanol.