The effects of chronic ethanol consumption on the formation of phosphatidylethanolamine molecular species and their appearance at the plasma membrane.

The purpose of our study was to determine whether chronic ethanol consumption affected membrane assembly by altering the formation of specific molecular species of phosphatidylethanolamine (PE) and their subsequent incorporation into the plasma membrane (PM). We investigated the effects on the PE species made by the two major pathways in hepatocytes: (1) from CDP-ethanolamine in the endoplasmic reticulum, and (2) by the decarboxylation of phosphatidylserine (PS) in the mitochondria. Ethanol consumption exerted significant effects on the formation of ethanolamine-derived PE species and affected mainly two species, the 16:0/22:6 and 18:0/20:4 species. In cultured hepatocytes from ethanol-fed rats labeled with [3H]ethanolamine for 0.25 to 4 hr, the amount of the [3H]16:0/22:6 PE species was decreased compared with that in control cells, whereas the amount of [3H]18:0/20:4 species was increased. The amount of the [3H]16:0/22:6 PE species on the cell surface was also decreased in hepatocytes from ethanol-fed rats, whereas the amount of [3H]18:0/20:4 species was increased. In contrast, the profile of [3H]PE species formed in cells treated with [3H]serine exhibited minor alterations, and the profile of the serine-derived [3H]PE species on the cells surface was not altered after 4 hr of labeling. The changes in ethanolamine-derived species were apparently caused by time-dependent alterations in the metabolic processes, because the presence of 110 mM ethanol in the culture media did not affect the profiles of [3H]PE species in cells from control or ethanol-fed rats and was not required to sustain the altered profiles. The results indicate that the synthesis of specific PE molecular species and their appearance on the PM may occur by compartmentalized processes which are distinguishable by different sensitivities to ethanol consumption. The results indicate that ethanol consumption may contribute alcoholic hepatic injury by interfering with the metabolism of specific PE molecular species and their assembly into the PM.