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Coumarin 7‐hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons.
Author(s) -
Pelkonen O,
Sotaniemi EA,
Ahokas JT
Publication year - 1985
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1985.tb02613.x
Subject(s) - coumarin , hydroxylation , microsome , enzyme , cytochrome p450 , cytochrome , biochemistry , chemistry , isozyme , guinea pig , enzyme inducer , biology , endocrinology , organic chemistry
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.