title: Globins Scavenge Sulfur Trioxide Anion Radical.
abstract: Ferrous myoglobin was oxidized by sulfur trioxide anion radical (STAR) during the free radical chain oxidation of sulfite. Oxidation was inhibited by the STAR scavenger GSH and by the heme ligand CO. Bimolecular rate constants for the reaction of STAR with several ferrous globins and biomolecules were determined by kinetic competition. Reaction rate constants for myoglobin, hemoglobin, neuroglobin, and flavohemoglobin are large at 38, 120, 2,600, and ≥ 7,500 × 10(6) m(-1) s(-1), respectively, and correlate with redox potentials. Measured rate constants for O2, GSH, ascorbate, and NAD(P)H are also large at ∼100, 10, 130, and 30 × 10(6) m(-1) s(-1), respectively, but nevertheless allow for favorable competition by globins and a capacity for STAR scavenging in vivo. Saccharomyces cerevisiae lacking sulfite oxidase and deleted of flavohemoglobin showed an O2-dependent growth impairment with nonfermentable substrates that was exacerbated by sulfide, a precursor to mitochondrial sulfite formation. Higher O2 exposures inactivated the superoxide-sensitive mitochondrial aconitase in cells, and hypoxia elicited both aconitase and NADP(+)-isocitrate dehydrogenase activity losses. Roles for STAR-derived peroxysulfate radical, superoxide radical, and sulfo-NAD(P) in the mechanism of STAR toxicity and flavohemoglobin protection in yeast are suggested.
authors.affiliation: Miami Valley Biotech, Dayton, Ohio 45402. Electronic address: paul.gardner@mvbiotech.com.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gardner
authors.affiliation: Miami Valley Biotech, Dayton, Ohio 45402.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gardner
authors.affiliation: Miami Valley Biotech, Dayton, Ohio 45402.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Gardner
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism; D005486:Flavin Mononucleotide / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005914:Globins / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007700:Kinetics; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013447:Sulfites / Q000378:metabolism; D013461:Sulfur Oxides / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D005609:Free Radicals; D006420:Hemeproteins; D029701:Saccharomyces cerevisiae Proteins; D013447:Sulfites; D013461:Sulfur Oxides; D005486:Flavin Mononucleotide; D005914:Globins; D007521:Isocitrate Dehydrogenase; D049308:Dioxygenases; C101796:YHB1 protein, S cerevisiae; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase; D005978:Glutathione; C011118:sulfur trioxide; C042345:hydrogen sulfite
keywords: free radicals; hemoglobin myoglobin; mitochondrial metabolism; sulfur; yeast metabolism