Globins Scavenge Sulfur Trioxide Anion Radical [Metabolism]

September 17th, 2015 by Gardner, P. R., Gardner, D. P., Gardner, A. P.

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 x 106 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 approximately 100, 10, 130 and 30 x 106 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 non-fermentable 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.