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

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Pelkonen O, Sotaniemi EA, Ahokas JT

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.

PubMed ID

3978021 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Metyrapone	Cytochrome P450 2A6	Protein	Humans	Unknown	Inhibitor	Details