Y. Amet et al., EVIDENCE THAT CYTOCHROME-P450 2E1 IS INVOLVED IN THE (OMEGA-1)-HYDROXYLATION OF LAURIC ACID IN RAT-LIVER MICROSOMES, Biochemical and biophysical research communications, 203(2), 1994, pp. 1168-1174
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.