Inhibition of rat liver monooxygenase activities by 2-methyl-1,4-naphthoquinone (menadione)

Toxicol Appl Pharmacol. 1990 Sep 1;105(2):333-9. doi: 10.1016/0041-008x(90)90194-y.


In rat liver microsomes, 2-methyl-1,4-naphthoquinone (menadione) inhibits cytochrome P450 (cyt P450)-mediated aniline-p-hydroxylation and aminopyrine-N-demethylation with Ki values of 12 and 14.5 microM, respectively. The inhibitions of aniline-p-hydroxylation and aminopyrine-N-demethylation are mixed uncompetitive-noncompetitive and mixed competitive-noncompetitive, respectively. NADP antagonizes the inhibitory effect of menadione on aniline-p-hydroxylase activity but not that on aminopyrine-N-demethylase activity. Menadione does not give rise to any spectral change of cyt P450, but modifies the type I binding spectrum induced by aminopyrine. In contrast, menadione does not change the type II binding spectrum induced by aniline. These results indicate that menadione may inhibit aniline-p-hydroxylase activity by acting as a substrate for NADPH-cyt P450 reductase in the place of cyt P450 and inhibit aminopyrine-N-demethylase activity by impairing the binding of aminopyrine to cyt P450.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyrine N-Demethylase / antagonists & inhibitors*
  • Aniline Hydroxylase / antagonists & inhibitors*
  • Animals
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism*
  • Kinetics
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • NADP / metabolism
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains
  • Spectrophotometry
  • Vitamin K / pharmacology*


  • Cytochrome P-450 Enzyme Inhibitors
  • Vitamin K
  • NADP
  • Cytochrome P-450 Enzyme System
  • Aniline Hydroxylase
  • Aminopyrine N-Demethylase