Coumarin 7-hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons.
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.
D000818:Animals; D000983:Antipyrine / Q000097:blood; D001189:Aryl Hydrocarbon Hydroxylases; D001571:Benzoflavones / Q000494:pharmacology; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D001571:Benzoflavones; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D000983:Antipyrine