title: Carbon monoxide promotes respiratory hemoproteins iron reduction using peroxides as electron donors.
abstract: The physiological role of the respiratory hemoproteins (RH), hemoglobin and myoglobin, is to deliver O(2) via its binding to their ferrous (Fe(II)) heme-iron. Under variety of pathological conditions RH proteins leak to blood plasma and oxidized to ferric (Fe(III), met) forms becoming the source of oxidative vascular damage. However, recent studies have indicated that both metRH and peroxides induce Heme Oxygenase (HO) enzyme producing carbon monoxide (CO). The gas has an extremely high affinity for the ferrous heme-iron and is known to reduce ferric hemoproteins in the presence of suitable electron donors. We hypothesized that under in vivo plasma conditions, peroxides at low concentration can assist the reduction of metRH in presence of CO. The effect of CO on interaction of metRH with hydrophilic or hydrophobic peroxides was analyzed by following Soret and visible light absorption changes in reaction mixtures. It was found that under anaerobic conditions and low concentrations of RH and peroxides mimicking plasma conditions, peroxides served as electron donors and RH were reduced to their ferrous carboxy forms. The reaction rates were dependent on CO as well as peroxide concentrations. These results demonstrate that oxidative activity of acellular ferric RH and peroxides may be amended by CO turning on the reducing potential of peroxides and facilitating the formation of redox-inactive carboxyRH. Our data suggest the possible role of HO/CO in protection of vascular system from oxidative damage.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Sher
authors.forename: Mati
authors.initials: M
authors.lastname: Shaklai
authors.forename: Nurith
authors.initials: N
authors.lastname: Shaklai
mesh_terms: D002248:Carbon Monoxide / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010545:Peroxides / Q000378:metabolism*; D013053:Spectrophotometry
chemical_list: D006420:Hemeproteins; D008077:Lipoproteins, LDL; D010545:Peroxides; D002248:Carbon Monoxide; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)