THE INDUCTION OF CYTOCHROME-P450 ISOFORM, CYP4A1, BY CLOFIBRATE COINCIDES WITH ACTIVATION OF ETHANOLAMINE-SPECIFIC PHOSPHOLIPID BASE-EXCHANGE REACTION IN RAT-LIVER MICROSOMES

Administration of a hypolipidaemic drug, clofibrate, to rats resulted, 24 h after a single intraperitoneal injection (250 mg/kg body weight) , in pronounced enhancement of the rate of phosphatidylethanolamine (P E) synthesis via the PE-specific base exchange (PEBE) reaction in live r microsomes. This was accompanied by 3.4-fold activation of microsoma l omega-hydroxylation of lauric acid by cytochrome P450 4A1 isoform (C YP4A1) and an increase in the protein content of this isoform in endop lasmic reticulum (KR) membranes. Since PE represents a class of phosph olipids (PL) prerequisite for proper functioning of CYP4A1, and the PE BE reaction is an inducible pathway of Pi, synthesis in hepatocytes un der metabolic stress, one may speculate that this reaction is switched on when extensive remodelling of PL molecular species or/and massive synthesis of lipid bilayer components for membrane assembly is require d.