title: Peroxidase-catalyzed halide ion oxidation.
abstract: The first complete mechanistic analysis of halide ion oxidation by a peroxidase was that of iodide oxidation by horseradish peroxidase. It was shown conclusively that a two-electron oxidation of iodide by compound I was occurring. This implied that oxygen atom transfer was occurring from compound I to iodide, forming hypoiodous acid, HOI. Searches were conducted for other two-electron oxidations. It was found that sulfite was oxidized by a two-electron mechanism. Nitrite and sulfoxides were not. If a competing substrate reduces some compound I to compound II by the usual one-electron route, then compound II will compete for available halide. Thus compound II oxidizes iodide to an iodine atom, I*, although at a slower rate than oxidation of I by compound I. An early hint that mammalian peroxidases were designed for halide ion oxidation was obtained in the reaction of lactoperoxidase compound II with iodide. The reaction was accelerated by excess iodide, indicating a co-operative effect. Among the heme peroxidases, only chloroperoxidase (for example from Caldariomyces fumago) and mammalian myeloperoxidase are able to oxidize chloride ion. There is not yet a consensus as to whether the chlorinating agent produced in a peroxidase-catalyzed reaction is hypochlorous acid (HOCl), enzyme-bound hypochlorous acid (either Fe-HOCl or X-HOCl where X is an amino acid residue), or molecular chlorine Cl2. A study of the nonenzymatic iodination of tyrosine showed that the iodinating reagent was either HOI or I2. It was impossible to tell which species because of the equilibria: [reaction: see text] The same considerations apply to product analysis of an enzyme-catalyzed reaction. Detection of molecular chlorine Cl2 does not prove it is the chlorinating species. If Cl2 is in equilibrium with HOCl then one cannot tell which (if either) is the chlorinating reagent. Examples will be shown of evidence that peroxidase-bound hypochlorous acid is the chlorinating agent. Also a recent clarification of the mechanism of reaction of myeloperoxidase with hydrogen peroxide and chloride along with accurate determination of the elementary rate constants will be discussed.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: H B
authors.initials: HB
authors.lastname: Dunford
mesh_terms: D000818:Animals; D002384:Catalysis; D002713:Chlorine / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007455:Iodine / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000502:physiology; D010544:Peroxidases / Q000502:physiology*
chemical_list: D002713:Chlorine; D007455:Iodine; D006861:Hydrogen Peroxide; D010544:Peroxidases; D009195:Peroxidase