Mechanism of the metabolism of 1,3-benzodioxoles to carbon monoxide.
Carbon monoxide is a minor product formed during the cytochrome P-450-catalyzed oxidation of 1,3-benzodioxoles. Studies with [2-13C]methylene 1,3-benzodioxoles established that the methylenic carbon of the 1,3-benzodioxole ring is the source of the carbon atom in the carbon monoxide, and an isotope effect of 1.7 to 2.0 was observed with [2-2H2]methylene derivatives. Incubations conducted in the presence of [18O]dioxygen and [18O]water showed that the oxygen atom in carbon monoxide arises from both oxygen and water. A mechanism consistent with these data has been proposed for carbon monoxide formation. It involves initial monooxygenation of the 1,3-benzodioxole to a 2-hydroxy derivative that subsequently forms a 2-hydroxyphenyl formate intermediate, which yields either carbon monoxide or formate. The proposed mechanism is discussed in terms of its possible relationship to the inhibitory activity of 1,3-benzodioxoles toward microsomal oxidation.
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003903:Deuterium; D004149:Dioxoles / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004149:Dioxoles; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D003903:Deuterium; C040539:1,3-benzodioxole; D010100:Oxygen