title: Oxidative heme protein-mediated nitroxyl (HNO) generation.
abstract: The distinct biological properties of nitroxyl (HNO) have focused research regarding the chemistry and biology of this redox relative of nitric oxide (NO). Much of HNO's biological activity appears to arise through modification of thiol-containing enzymes and proteins and reactions with iron-heme proteins. The reactions of HNO with hemoglobin and myoglobin serve as a general model for understanding HNO reactivity with other heme proteins. Interaction of HNO with catalase and soluble guanylate cyclase may have biological roles. While endogenous HNO formation remains to be described, we summarize work that reveals HNO formation through oxidative heme protein metabolism of various nitrogen-containing substrates including hydroxylamine, hydroxyurea, hydroxamic acids, cyanamide, and sodium azide. Depending on the enzyme, the nascent HNO reductively nitrosylates the heme protein or escapes the heme pocket as HNO. Such results define an alternative metabolism-based route to HNO that may inform endogenous HNO production.
authors.affiliation: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Reisz
authors.forename: Erika
authors.initials: E
authors.lastname: Bechtold
authors.forename: S Bruce
authors.initials: SB
authors.lastname: King
mesh_terms: D002374:Catalase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D009211:Myoglobin / Q000378:metabolism; D009589:Nitrogen Oxides / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D006420:Hemeproteins; D006454:Hemoglobins; D009211:Myoglobin; D009589:Nitrogen Oxides; D003577:Cytochrome P-450 Enzyme System; D006735:Horseradish Peroxidase; D002374:Catalase; D003576:Electron Transport Complex IV; D006162:Guanylate Cyclase; C039900:nitroxyl