Hydrogen peroxide-dependent oxidation metabolism of 1-methyl-2-mercaptoimidazole (methimazole) catalysed by myeloperoxidase.
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 hyochlorous acid produced by the myeloperoxidase-H2O2-Cl- system giving bis-(1-methyl-2-imidazolyl)disulphide (MMI-disulphide) as an initial product, which gradually underwent disproportionation 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.
Sayo
H
H
Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Saito
M
M
D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology; D008713:Methimazole / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D011189:Potassium Chloride / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
D004220:Disulfides; D008713:Methimazole; D011189:Potassium Chloride; D006861:Hydrogen Peroxide; D009195:Peroxidase