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 (omega-1)-hydroxylation of lauric acid in rats treated with pyridine, pyrazole, acetone, ethanol and 3-methylcholanthrene. The (omega-1)-hydroxylase activity was strongly correlated with chlorzoxazone 6-hydroxylation (r = 0.76) and 4-nitrophenol-hydroxylase (r = 0.91). Both these activities are carried out by CYP2E1. (omega-1) hydroxylase activity was inhibited by ethanol (Ki = 3.5 mM), dimethylsulfoxide and diethyldithiocarbamate. Furthermore, polyclonal antibody directed against rat CYP2E1 inhibited (omega-1)-hydroxylation by more than 90% while it had no effect on the omega-hydroxylation. These results suggest that the (omega-1)-hydroxylation of lauric acid is mediated principally by the CYP2E1 enzyme in rat liver microsomes.
Amet
Y
Y
Equipe d'accueil DRED, Laboratoire Biochimie-Nutrition, Faculté de Médecine, Brest, France.
Berthou
F
F
Goasduff
T
T
Salaun
J P
JP
Le Breton
L
L
Menez
J F
JF
D000096:Acetone / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D006900:Hydroxylation; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007850:Lauric Acids / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D007850:Lauric Acids; D011720:Pyrazoles; D011725:Pyridines; C030358:lauric acid; D000096:Acetone; D000431:Ethanol; C031280:pyrazole; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; C023666:pyridine