Hydrogen peroxide-dependent oxidative metabolism of 1-methy1-2-mercaptoimidazole (methimazole) catalysed by myeloperoxidase

Abstract

1. Myeloperoxidase catalysed the H₂O₂-supported oxidation of 1-methyl-2-mercaptoimidazole (MMI) in the presence of Cl⁻. The rate of MMI oxidation was determined by monitoring a decrease in the absorbance at 251 nm. The pH optimum of the oxidation was around 4.5. The rate of MMI oxidation showed typical Michaelis-Menten saturation kinetics with respect to H₂O₂. Inhibition by excess H₂O₂ was not seen.

2. When the H₂O₂/MMI ratio was 0.5, MMI was oxidized by hypochlorous acid produced by the myeloperoxidase-H₂O₂-Cl⁻ system giving bis-(1-methyl-2-imidazolyl)disulphide (MMI-disulphide) as an initial product, which gradually underwent disproportionatioh and subsequent hydrolysis giving 1-methylimidazole and MMI as the final products stoichiometrically.

3. When the H₂O₂/MMI ratio was one or above, hypochlorous acid produced in excess reacted with MMI-disulphide to give unidentified compounds. The sum of the amounts of 1-methylimidazole formed and of MMI reformed was less than 81% of the MMI added.