S-oxidation of thioureylenes catalyzed by a microsomal flavoprotein mixed-function oxidase

A flavoprotein mixed-function oxidase that catalyzes NADPH-dependent oxidation of thioureylenes by oxygen was isolated from pig liver microsomes and shown to be identical with the flavoprotein amine oxidase isolated earlier. The oxidation products obtained from the thioureylene, methimazole, were identified as N-methylimidazole and sulfite. The stoichiometry of the reaction indicated that 2 moles NADPH and 2 moles oxygen were required for each mole of methimazole oxidized. In addition to all of the thioureylenes tested, the flavoprotein also catalyzes the oxidation of dithiothreotol and its cyclic disulfide. At the pH optimum for the flavoprotein mixed-function oxidase, virtually all of the methimazole metabolized by homogenates of pig liver appears to be catalyzed by this membrane-bound oxidase. The methimazole oxidase activity also appears to correlate with the concentration of this oxidase in microsomes isolated from homogenates of rat, rabbit and guinea-pig liver, but species differences in the response of this mixed-function oxidase to activators were observed.