Evidence that cytochrome P450 2E1 is involved in the (omega-1)-hydroxylation of lauric acid in rat liver microsomes

Biochem Biophys Res Commun. 1994 Sep 15;203(2):1168-74. doi: 10.1006/bbrc.1994.2305.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetone / pharmacology
  • Animals
  • Binding, Competitive
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Induction / drug effects
  • Ethanol / pharmacology
  • Hydroxylation
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Lauric Acids / metabolism*
  • Male
  • Methylcholanthrene / pharmacology
  • Microsomes, Liver / enzymology*
  • Oxidoreductases, N-Demethylating / metabolism*
  • Pyrazoles / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Isoenzymes
  • Lauric Acids
  • Pyrazoles
  • Pyridines
  • lauric acid
  • Acetone
  • Ethanol
  • pyrazole
  • Methylcholanthrene
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Oxidoreductases, N-Demethylating
  • pyridine