Vitamin K epoxide reductase activity in the metabolism of epoxides.
The importance of vitamin K epoxide reductase for the metabolism of a range of structurally diverse epoxides has been investigated. Vitamin K1 epoxide is reduced by rat liver microsomes at a rate of 0.47 nmoles/g liver/min. The rate of menadione oxide reduction is not significantly higher than the non-enzymatic reduction rate. No measurable reduction of benzo[a]pyrene 4,5-oxide, benzo[a]pyrene 7,8-oxide, phenanthrene 9,10-oxide, styrene 7,8-oxide, and dieldrin has been detected, nor could trichothecene T-2 toxin inhibit reduction of vitamin K1 epoxide. Thus, vitamin K epoxide reductase is very specific for vitamin K1 epoxide. Taking into account the range of structurally diverse epoxides investigated and the high specific activities of microsomal epoxide hydrolase and cytosolic glutathione transferase for these epoxides it may be concluded that vitamin K epoxide reductase, in all likelihood, generally does not significantly contribute to the control of epoxides metabolically formed from xenobiotics.
D000818:Animals; D004851:Epoxide Hydrolases / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014239:Trichloroepoxypropane / Q000494:pharmacology; D010837:Vitamin K 1 / Q000031:analogs & derivatives / Q000494:pharmacology; D064417:Vitamin K Epoxide Reductases
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; C016186:vitamin K1 oxide; D014239:Trichloroepoxypropane; D010837:Vitamin K 1; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D004851:Epoxide Hydrolases