title: The catabolic fate of nitric oxide: the nitric oxide oxidase and peroxynitrite reductase activities of cytochrome oxidase.
abstract: Stimulation of cardiomyocytes to endogenously evolve nitric oxide is shown by microsensor measurements on single cells to lead to transient nitric oxide concentrations of a few hundred nanomolar. At these submicromolar concentrations, no evidence could be found for the expected reaction between nitric oxide generated and the oxymyoglobin present in the cells: nitric oxide + oxymyoglobin --> nitrate + metmyoglobin. No metmyoglobin formation was detected by electron paramagnetic resonance spectroscopy, and microsensor measurements revealed near quantitative conversion of the nitric oxide to nitrite rather than nitrate ion. Moreover, the rate of nitrite formation is shown to be too rapid to be accounted for by non-enzymatic means. The essentially quantitative and rapid catabolism of nitric oxide to nitrite ion can plausibly be explained on the basis of a cycle of reactions catalyzed by cytochrome c oxidase. It is demonstrated with the purified hemoproteins in vitro that the terminal oxidase can outcompete oxymyoglobin for available nitric oxide. It is proposed that under normal physiological and most pathological (non-inflammatory) conditions, reaction with cytochrome c oxidase is the major route by which NO is removed from mitochondria-rich cells.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania 15261, USA. lip10@pitt.edu
authors.forename: Linda L
authors.initials: LL
authors.lastname: Pearce
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kanai
authors.forename: Lori A
authors.initials: LA
authors.lastname: Birder
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Pitt
authors.forename: Jim
authors.initials: J
authors.lastname: Peterson
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D003576:Electron Transport Complex IV / Q000378:metabolism; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007700:Kinetics; D008786:Metmyoglobin / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D009206:Myocardium / Q000166:cytology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D013696:Temperature
chemical_list: D003574:Cytochrome c Group; D007477:Ions; D009566:Nitrates; D009573:Nitrites; D008786:Metmyoglobin; D009569:Nitric Oxide; D010088:Oxidoreductases; C034747:nitric-oxide reductase; C109110:peroxynitrite reductase; D003576:Electron Transport Complex IV; D002118:Calcium