title: Vascular peroxidase 1 catalyzes the formation of hypohalous acids: characterization of its substrate specificity and enzymatic properties.
abstract: The heme-containing peroxidase family comprises eight members in humans. The physiological and pathophysiological roles of heme-containing peroxidases are not well understood. Phagocyte-derived myeloperoxidase (MPO) utilizes chloride and bromide, in the presence of hydrogen peroxide (H(2)O(2)), to generate hypochlorous acid and hypobromous acid, potent oxidizing species that are known to kill invading pathogens. Vascular peroxidase 1 (VPO1) is a new member of the heme-containing peroxidase family; VPO1 is highly expressed in the cardiovascular system, lung, liver, pancreas, and spleen. However, functional roles of VPO1 have not been defined. In this report, we demonstrate the capacity for VPO1 to catalyze the formation of hypohalous acids, and characterize its enzymatic properties. VPO1, like MPO but unlike lactoperoxidase, is able to generate hypochlorous acid, hypobromous acid, and hypothiocyanous acid in the presence of H(2)O(2). Under physiological pH and concentrations of halides (100μM KBr, 100μM KSCN, and 100mM NaCl), VPO1 utilizes approximately 45% of H(2)O(2) for the generation of hypobromous acid, 35% for hypothiocyanous acid, and 18% for hypochlorous acid. The specific activity of VPO1 is ∼10- to 70-fold lower than that of MPO, depending on the specific substrate. These studies demonstrate that the enzymatic properties and substrate specificity of VPO1 are similar to MPO; however, significantly lower catalytic rate constants of VPO1 relative to MPO suggest the possibility of other physiologic roles for this novel heme-containing peroxidase.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, AL 35294, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Zehong
authors.initials: Z
authors.lastname: Cao
authors.forename: Guogang
authors.initials: G
authors.lastname: Zhang
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
authors.forename: Guangjie
authors.initials: G
authors.lastname: Cheng
mesh_terms: D055162:Biocatalysis; D001959:Bromates / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000032:analysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D006997:Hypochlorous Acid / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism*; D013379:Substrate Specificity; D013654:Taurine / Q000378:metabolism; D013861:Thiocyanates / Q000737:chemistry / Q000378:metabolism*; D000097423:Peroxidasin
chemical_list: D001959:Bromates; D006418:Heme; D006861:Hydrogen Peroxide; D006997:Hypochlorous Acid; D009195:Peroxidase; D010544:Peroxidases; D013654:Taurine; D013861:Thiocyanates; C517667:hypothiocyanous acid; C535215:PXDN protein, human; D000097423:Peroxidasin; C027664:hypobromous acid