title: Superoxide-dependent oxidation of melatonin by myeloperoxidase.
abstract: Myeloperoxidase uses hydrogen peroxide to oxidize numerous substrates to hypohalous acids or reactive free radicals. Here we show that neutrophils oxidize melatonin to N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) in a reaction that is catalyzed by myeloperoxidase. Production of AFMK was highly dependent on superoxide but not hydrogen peroxide. It did not require hypochlorous acid, singlet oxygen, or hydroxyl radical. Purified myeloperoxidase and a superoxide-generating system oxidized melatonin to AFMK and a dimer. The dimer would result from coupling of melatonin radicals. Oxidation of melatonin was partially inhibited by catalase or superoxide dismutase. Formation of AFMK was almost completely eliminated by superoxide dismutase but weakly inhibited by catalase. In contrast, production of melatonin dimer was enhanced by superoxide dismutase and blocked by catalase. We propose that myeloperoxidase uses superoxide to oxidize melatonin by two distinct pathways. One pathway involves the classical peroxidation mechanism in which hydrogen peroxide is used to oxidize melatonin to radicals. Superoxide adds to these radicals to form an unstable peroxide that decays to AFMK. In the other pathway, myeloperoxidase uses superoxide to insert dioxygen into melatonin to form AFMK. This novel activity expands the types of oxidative reactions myeloperoxidase can catalyze. It should be relevant to the way neutrophils use superoxide to kill bacteria and how they metabolize xenobiotics.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Valdecir F
authors.initials: VF
authors.lastname: Ximenes
authors.forename: Sueli de O
authors.initials: SO
authors.lastname: Silva
authors.forename: Maria R
authors.initials: MR
authors.lastname: Rodrigues
authors.forename: Luiz H
authors.initials: LH
authors.lastname: Catalani
authors.forename: Ghassan J
authors.initials: GJ
authors.lastname: Maghzal
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kettle
authors.forename: Ana
authors.initials: A
authors.lastname: Campa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D002374:Catalase / Q000737:chemistry; D002384:Catalysis; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006418:Heme / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology; D017665:Hydroxyl Radical; D006997:Hypochlorous Acid / Q000737:chemistry / Q000378:metabolism; D007735:Kynuramine / Q000031:analogs & derivatives / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D013058:Mass Spectrometry; D008550:Melatonin / Q000737:chemistry*; D008956:Models, Chemical; D009504:Neutrophils / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D010126:Ozone / Q000737:chemistry; D009195:Peroxidase / Q000737:chemistry*; D011485:Protein Binding; D013481:Superoxides / Q000737:chemistry*; D013654:Taurine / Q000031:analogs & derivatives / Q000737:chemistry; D013997:Time Factors; D014969:Xanthine Oxidase / Q000737:chemistry
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D013481:Superoxides; D013654:Taurine; D017665:Hydroxyl Radical; D007735:Kynuramine; D006418:Heme; C043410:N-chlorotaurine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D010126:Ozone; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D014969:Xanthine Oxidase; D008550:Melatonin; D010100:Oxygen