title: Mechanism of reaction of chlorite with mammalian heme peroxidases.
abstract: This study demonstrates that heme peroxidases from different superfamilies react differently with chlorite. In contrast to plant peroxidases, like horseradish peroxidase (HRP), the mammalian counterparts myeloperoxidase (MPO) and lactoperoxidase (LPO) are rapidly and irreversibly inactivated by chlorite in the micromolar concentration range. Chlorite acts as efficient one-electron donor for Compound I and Compound II of MPO and LPO and reacts with the corresponding ferric resting states in a biphasic manner. The first (rapid) phase is shown to correspond to the formation of a MPO-chlorite high-spin complex, whereas during the second (slower) phase degradation of the prosthetic group was observed. Cyanide, chloride and hydrogen peroxide can block or delay heme bleaching. In contrast to HRP, the MPO/chlorite system does not mediate chlorination of target molecules. Irreversible inactivation is shown to include heme degradation, iron release and decrease in thermal stability. Differences between mammalian peroxidases and HRP are discussed with respect to differences in active site architecture and heme modification.
authors.affiliation: Department of Chemistry, Division of Biochemistry, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Christa
authors.initials: C
authors.lastname: Jakopitsch
authors.affiliation: Department of Chemistry, Division of Biochemistry, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Katharina F
authors.initials: KF
authors.lastname: Pirker
authors.affiliation: Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstr 16-18, D-04107 Leipzig, Germany; Translational Centre for Regenerative Medicine, University of Leipzig, Philipp-Rosenthal-Strasse 55, D-04103 Leipzig, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Flemmig
authors.affiliation: Department of Chemistry, Division of Biochemistry, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofbauer
authors.affiliation: Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstr 16-18, D-04107 Leipzig, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Schlorke
authors.affiliation: Department of Chemistry, Division of Biochemistry, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Furtmüller
authors.affiliation: Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstr 16-18, D-04107 Leipzig, Germany; Translational Centre for Regenerative Medicine, University of Leipzig, Philipp-Rosenthal-Strasse 55, D-04103 Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Arnhold
authors.affiliation: Department of Chemistry, Division of Biochemistry, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, A-1190 Vienna, Austria. Electronic address: christian.obinger@boku.ac.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Obinger
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D020134:Catalytic Domain; D002417:Cattle; D002712:Chlorides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D006418:Heme / Q000737:chemistry; D006735:Horseradish Peroxidase / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D007784:Lactoperoxidase / Q000737:chemistry*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry*; D017433:Protein Structure, Secondary; D019163:Reducing Agents / Q000737:chemistry*
chemical_list: D002712:Chlorides; D019163:Reducing Agents; D006418:Heme; D006735:Horseradish Peroxidase; D007784:Lactoperoxidase; D009195:Peroxidase; C001599:chlorite
keywords: Chlorine dioxide; Chlorite; Hypochlorous acid; Lactoperoxidase; Myeloperoxidase; Oxoferin