Oxidative heme protein-mediated nitroxyl (HNO) generation

Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
Dalton Transactions (Impact Factor: 4.2). 06/2010; 39(22):5203-12. DOI: 10.1039/c000980f
Source: PubMed


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.

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Available from: Erika Bechtold
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    • "Oxidation of NH 2 OH can serve as an alternative source for HNO production. The generation of high-valent ironoxo complexes from the reaction of ferric hemes (usually peroxidases or catalases) with hydrogen peroxide can oxidize NH 2 OH to HNO (Scheme 8) [27, 58]. "
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    • "However, this creates the possibility that the oxidant is not NO itself but a reactive species derived from NO autoxidation. Although there is evidence for NO − (HNO) formation in the presence of some heme proteins, the source is typically a strong reductant such as hydroxyurea or cyanamide [17]. Ferricytochrome c reacts with HNO to give NO and ferrous cytochrome c[18], suggesting the driving force in this system acts in the direction of reduction of cytochrome c, not its oxidation . "
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