title: Electrochemical reduction of ferrous alpha-verdoheme in complex with heme oxygenase-1.
abstract: The heme oxygenase (HO) reaction consists of three successive oxygenation reactions, i.e. heme to alpha-hydroxyheme, alpha-hydroxyheme to verdoheme, and verdoheme to biliverdin-iron chelate. Of these, the least understood step is the conversion of verdoheme to biliverdin-iron chelate. For the cleavage of the oxaporphyrin ring of ferrous verdoheme, involvement of a verdoheme pi-neutral radical has been proposed. To probe this hypothetical mechanism in the HO reaction, we performed electrochemical reduction of ferrous verdoheme complexed with rat HO-1 under anaerobic conditions. On the basis of the electrochemical spectral changes, the midpoint potential for the one-electron reduction of the oxaporphyrin ring of ferrous verdoheme was found to be -0.47+/-0.01 V vs the normal hydrogen electrode (NHE). Because this potential is far lower than those of both flavins of NADPH-cytochrome P450 reductase, and of NADPH, it is concluded that the one-electron reduction of the oxaporphyrin ring of ferrous verdoheme is unlikely to occur and that the formation of the pi-neutral radical cannot be the initial step in the degradation of verdoheme by HO. Rather, it appears more reasonable to consider an alternative mechanism in which binding of O(2) to the ferrous iron of verdoheme is the first step in the degradation of verdoheme.
authors.affiliation: Department of Medical Biochemistry, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sato
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Higashimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Masakazu
authors.initials: M
authors.lastname: Sugishima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Graham
authors.initials: G
authors.lastname: Palmer
authors.forename: Masato
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D004563:Electrochemistry / Q000379:methods*; D006418:Heme / Q000031:analogs & derivatives* / Q000737:chemistry; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry*; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D011994:Recombinant Proteins; C099547:verdoheme; D006418:Heme; D006419:Heme Oxygenase (Decyclizing)