Changes in microsomal membrane microviscosity and phospholipid methyltransferases during rat liver regeneration

During regeneration of rat liver newly synthesized molecules of drug-metabolizing enzymes, like cytochrome P450, are incorporated into proliferating endoplasmic reticulum (ER). Decreased membrane microviscosity facilitates incorporation of the enzyme-protein molecules into the phospholipid matrix of ER. The microviscosity of membranes is altered by: (1) changed ratios of phospholipid to cholesterol, (2) unsaturation of fatty acids in phospholipids, and (3) methylation of phospholipids. Alterations are known to occur in (1) and (2) in the plasma membrane of proliferating cells. Microviscosity and phospholipid methyltransferases in ER have not been investigated during liver regeneration. Therefore, microviscosity and S-adenosyl-L-methionine (SAM) mediated methylation of phosphatidylethanolamine to phosphatidyl-N-methylethanolamine (PME) and phosphatidylcholine (PC) were measured using microsomal membranes of regenerating rat livers at 6-96 h after partial hepatectomy. In the methylated phospholipids, the proportion of PME increased by 3-9% at 1 microM SAM, and, at 200 microM SAM, the proportion of PC decreased by about 5-10% at 12-24 h. Two phase transitions were observed with microsomal membranes between 20 and 40 degrees C. In synthetic liposomes containing PE, PME and PC, microviscosity decreased when the proportion of PME increased or the proportion of PC decreased. Therefore, alterations in phospholipid methyltransferases and consequent changes in membrane phospholipid methylation may contribute to increased membrane fluidity during cell proliferation and incorporation of drug-metabolizing enzymes into ER.