title: Comparison of the reactivity of nitric oxide and nitroxyl with heme proteins. A chemical discussion of the differential biological effects of these redox related products of NOS.
abstract: Investigations on the biological effects of nitric oxide (NO) derived from nitric oxide synthase (NOS) have led to an explosion in biomedical research over the last decade. The chemistry of this diatomic radical is key to its biological effects. Recently, nitroxyl (HNO/NO(-)) has been proposed to be another important constituent of NO biology. However, these redox siblings often exhibit orthogonal behavior in physiological and cellular responses. We therefore explored the chemistry of NO and HNO with heme proteins in different redox states and observed that HNO favors reaction with ferric heme while NO favors ferrous, consistent with previous reports. Further results show that HNO and NO were equally effective in inhibiting cytochrome P450 activity, which involves ferric and ferrous complexes. The differential chemical behavior of NO and HNO toward heme proteins provides insight into mechanisms of activity that not only helps explain some of the opposing effects observed in NOS-mediated events, but offers a unique control mechanism for the biological action of NO.
authors.affiliation: Tumor Biology Section, Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room B3-B69, Bethesda, MD 20892, USA.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Miranda
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Nims
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Thomas
authors.forename: Michael G
authors.initials: MG
authors.lastname: Espey
authors.forename: Deborah
authors.initials: D
authors.lastname: Citrin
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bartberger
authors.forename: Nazareno
authors.initials: N
authors.lastname: Paolocci
authors.forename: Jon M
authors.initials: JM
authors.lastname: Fukuto
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
authors.forename: David A
authors.initials: DA
authors.lastname: Wink
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism*; D058085:Iron Compounds / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D006420:Hemeproteins; D058085:Iron Compounds; D009589:Nitrogen Oxides; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D003577:Cytochrome P-450 Enzyme System; D019001:Nitric Oxide Synthase; C039900:nitroxyl