title: The inhibition of corrinoid-catalyzed oxidation of mercaptoethanol by methyl iodide: mechanistic implications.
abstract: The cobalamin coenzymes (5'-deoxyadenosyl- and methylcobalamin) and their cobinamide counterparts (5'-deoxyadenosyl- and methylcobinamide) catalyze the oxidation of 2-mercaptoethanol to its disulfide with hydrogen peroxide formation under aerobic conditions. The reactions are blocked by methyl iodide. Inhibition by methyl iodide is apparently due to the formation of the trans dialkyl corrinoids: methyl(adenosyl)cobalamin, dimethylcobalamin, methyl(adenosyl)cobinamide, and dimethylcobinamide, respectively. When the reaction system is illuminated with visible light, inhibition is released and a dramatic enhancement in the rate of oxygen consumption occurs. For reactions catalyzed by adenosyl- and methylcobalamin and then inhibited by methyl iodide, the rates observed during photolysis approach those obtained with aquacobalamin. For reactions catalyzed by adenosyl- and methylcobinamide and then inhibited by methyl iodide, the rates observed during photlysis approach those obtained with diaquacobinamide. Thus, both trans axial carbon-cobalt bonds in the putative dialkyl corrinoid are homolyzed during photolysis. In contrast to these results, the catalysis of the aerobic oxidation of 2-mercaptoethanol by aquacobalamin is only weakly inhibited by methyl iodide. This observation suggests that aquacob(II)alamin is produced during the catalysis of this reaction. Superoxide, the anticipated product of the reaction between aquacob(II)alamin and dioxygen, is formed during aquacobalamin-catalyzed 2-mercaptoethanol oxidation since superoxide dismutase decreases the rate of oxygen consumption by 50%. However, the enzyme has no effect on oxygen uptake during reactions catalyzed by cobalamin coenzymes and their cobinamide counterparts. These corrinoid catalysts apparently transfer two electrons to dioxygen from cobalt(I) intermediates formed during the reactions. Nitrogenous bases inhibit corrinoid-catalyzed thiol oxidation by competing with 2-mercaptoethanol for axial-ligand coordination sites on the catalyst. In contrast to the inhibition observed with methyl iodide, visible light has no effect on the inhibition obtained with nitrogenous bases.
authors: Department of Cell Biology, Cleveland Clinic Foundation, Ohio 44195.
authors: D W
authors: DW
authors: Jacobsen
authors: E H
authors: EH
authors: Pezacka
authors: K L
authors: KL
authors: Brown
mesh_terms: D002384:Catalysis; D003035:Cobalt / Q000378:metabolism; D003067:Coenzymes / Q000378:metabolism; D045728:Corrinoids; D004220:Disulfides / Q000378:metabolism; D004579:Electron Transport; D006847:Hydrocarbons, Iodinated / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D008623:Mercaptoethanol / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010782:Photolysis; D013482:Superoxide Dismutase / Q000494:pharmacology; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D003067:Coenzymes; D045728:Corrinoids; D004220:Disulfides; D006847:Hydrocarbons, Iodinated; D003035:Cobalt; D008623:Mercaptoethanol; D006861:Hydrogen Peroxide; C014055:methyl iodide; D013482:Superoxide Dismutase; D014805:Vitamin B 12; D010100:Oxygen