EVIDENCE THAT CYTOCHROME-P450 2E1 IS INVOLVED IN THE (OMEGA-1)-HYDROXYLATION OF LAURIC ACID IN RAT-LIVER MICROSOMES

The present study examined changes in hepatic CYP2E1 content and (omeg a-1)-hydroxylation of lauric acid in rats treated with pyridine, pyraz ole, acetone, ethanol and 3-methylcholanthrene. The (omega-1)-hydroxyl ase activity was strongly correlated with chlorzoxazone 6-hydroxylatio n (r = 0.76) and 4-nitrophenol-hydroxylase (r = 0.31). Both these acti vities are carried out by CYP2E1. (omega-1) hydroxylase activity was i nhibited by ethanol (Ki = 3.5 mM), dimethylsulfoxide and diethyldithio carbamate. Furthermore, polyclonal antibody directed against rat CYP2E 1 inhibited (omega-1)-hydroxylation by more than 90 % while it had no effect on the omega-hydroxylation. These results suggest that the (ome ga-1)-hydroxylation of lauric acid is mediated principally by the CYP2 E1 enzyme in rat liver microsomes. (C) 1994 Academic Press, Inc.