Kinetics of the inhibition of styrene oxide and benzo(a)pyrene-4,5-oxide hydration in rat liver microsomes by cadmium.
The kinetics of the inhibition by cadmium of styrene oxide and benzo(a)pyrene-4,5-oxide hydration were studied in a microsomal preparation from rat liver. Cadmium inhibited the hydration of styrene oxide in an apparently noncompetitive manner, whereas the inhibition of benzo(a)pyrene-4,5-oxide hydration showed a competitive mechanism. Styrene oxide inhibited the hydration of benzo(a)pyrene-4,5-oxide competitively and cyclohexene oxide inhibited the hydration of both styrene oxide and benzo(a)pyrene-4,5-oxide competitively. The present data suggest that cadmium is bound near the active centre of the enzyme. Occupation of this site by cadmium inhibits the enzymic hydration of the polycyclic benzo(a)pyrene-4,5-oxide molecule competitively, and that of the smaller monocyclic alkene oxide of styrene noncompetitively. The estimated Ki values were below 10 mu mol for hydration of both substrates indicating that cadmium is a very potent inhibitor of epoxide hydration.
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology; D053138:Cyclohexenes; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D004852:Epoxy Compounds / Q000378:metabolism* / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000378:metabolism*; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats
D001580:Benzopyrenes; D003510:Cyclohexanes; D053138:Cyclohexenes; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D002104:Cadmium; C007193:cyclohexene oxide; C006707:benzo(a)pyrene 4,5-epoxide; C013690:styrene oxide; D004851:Epoxide Hydrolases