Changes in phospholipid methyltransferases and membrane microviscosity during induction of rat liver microsomal cytochrome P-450 by phenobarbital and 3-methylcholanthrene.

Rat liver microsomes contained two methyltransferases which converted phosphatidylethanolamine (PE) to phosphatidylcholine (PC). The first methyltransferase converted PE to phosphatidyl-N-methylethanolamine (PME) and the second methyltransferase converted PME to PC. Previous work has shown that increased PME synthesis decreases membrane microviscosity. Therefore, changes in the rat liver microsomal cytochrome P-450, phospholipid methyltransferases and membrane microviscosity after induction by phenobarbital and 3-methylcholanthrene were studied. Phenobarbital and 3-methylcholanthrene increased cytochrome P-450 levels 2- to 3-fold. At low SAM concentration, the proportion of PME among the total phospholipids formed increased significantly, and at a high SAM concentration, the proportion of PC among the total phospholipids formed decreased significantly in microsomes of treated rats. Treatment of rats with phenobarbital and 3-methylcholanthrene also decreased microviscosities of the microsomal membranes and liposomes which were prepared from phospholipids extracted from the microsomes. In synthetic liposomes containing PE, PME and PC, microviscosity decreased when the proportion of PME was increased or the proportion of PC was decreased. These results suggest that the membrane fluidity increases with phenobarbital and 3-methylcholanthrene treatment, and changes in phospholipid methyltransferases may contribute to the process of enzyme induction. During induction with phenobarbital, all three factors known to increase membrane fluidity (linoleic acid content, the formation of phosphatidyl-N-methylethanolamine, and decreases in the cholesterol/phospholipid ratio) contribute to the decrease in microviscosity. During induction with 3-methylcholanthrene, alterations in phospholipid methylation is possibly the primary cause of the decrease in membrane microviscosity.