The role of anionic phospholipids in membrane adaptation to ethanol

In rats chronically fed-ethanol, liver microsomes and mitochondria, brain synaptosomes and reconstituted vesicles of their respective membrane phospholipids are resistant to disordering by ethanol in vitro (membrane tolerance) after 35 days of ethanol exposure. (Taraschi et al, 1986a; Rottenberg et al, 1981). Specific phospholipids from ethanol-fed rats, i.e. phosphatidylinositol (PI) from liver microsomes, cardiolipin (CL) from hepatic mitochondria and phosphatidylserine (PS) from brain synaptosomes confer tolerance to reconstituted vesicles of membrane phospholipids from control rats. In liver microsomes, PI was the only lipid that exhibited a significant decrease in both the polyunsaturate pool and the ratio of the total olefinic content to the saturated fatty acid content. The fatty acid composition of cardiolipin was perturbed by chronic ethanol administration as evidenced by a significant increase in oleic acid (18:1) and a significant decrease in linoleic acid (18:2). These alterations produced a more saturated cardiolipin with a decreased (4.4%) unsaturation index (UI) and a 60% reduction in the UI/saturated fatty acid index. These fatty acid modifications, which arise in response to long term ethanol ingestion, represent an adaptive shift in lipid metabolic pathways that do not appear to be (solely) responsible for membrane tolerance.