Coumarin 7-hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons

Br J Clin Pharmacol. 1985 Jan;19(1):59-66. doi: 10.1111/j.1365-2125.1985.tb02613.x.

Abstract

Coumarin 7-hydroxylation and other cytochrome P-450-associated enzyme activities were studied in human liver biopsy homogenates and compared with activities in livers of other species. Coumarin 7-hydroxylation is extraordinarily active in human liver biopsy samples in vitro. Activity is lower in mouse, rabbit or guinea pig liver and essentially absent in rat liver. Cytochrome P-450 content and other associated enzyme activities were higher in animals. Coumarin 7-hydroxylation is induced by phenobarbitone in mouse liver, but no significant increase was seen in human or rat liver after exposure to inducers. Correlations amongst coumarin 7-hydroxylase, aryl hydrocarbon hydroxylase, 7-ethoxycoumarin O-deethylase and cytochrome P-450 are statistically significant (r values from 0.56 to 0.73), but do not permit the conclusion, that the same P-450 form catalyzes all the reactions studied. The correlations between coumarin hydroxylation and antipyrine half-life or clearance are statistically significant, but not good enough for predictive purposes. Coumarin 7-hydroxylase in human liver is inhibited by alpha-naphthoflavone, SKF 525A, metyrapone and aniline.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipyrine / blood
  • Aryl Hydrocarbon Hydroxylases*
  • Benzoflavones / pharmacology
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Guinea Pigs
  • Humans
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Microsomes, Liver / enzymology*
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Mixed Function Oxygenases / metabolism*
  • Proadifen / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Species Specificity

Substances

  • Benzoflavones
  • alpha-naphthoflavone
  • Cytochrome P-450 Enzyme System
  • Proadifen
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2A6
  • Antipyrine