title: Interactions of the anesthetic nitrous oxide with bovine heart cytochrome c oxidase. Effects on protein structure, oxidase activity, and other properties.
abstract: The interactions of nitrous oxide with cytochrome c oxidase isolated from bovine heart muscle have been investigated in search of an explanation for the inhibition of mitochondrial respiration by the inhalation anesthetic. Oxidase activity of the isolated enzyme is partially and reversibly reduced by nitrous oxide. N2O molecules are shown by infrared spectroscopy to occupy sites within the oxidase. Occupancy of sites within the protein by N2O has no observed effects on visible Soret spectra or on the O2 reaction site; no evidence is found for N2O serving as a ligand to a metal. The anesthetic does not substitute for O2 as an oxygen atom donor in either the cytochrome c oxidase or carbon monoxide dioxygenase reactions catalyzed by the enzyme. N2O appears to affect oxidase activity by reducing the rate of electron transfer from cytochrome c to the O2 reaction site rather than by interfering directly with the reduction of O2 to water. Cytochrome c oxidase represents a target site for nitrous oxide and possibly other anesthetics, and the inhibition of oxidase activity may contribute significantly to the anesthetic and/or toxic effects of these substances.
authors.affiliation: Department of Biochemistry, Colorado State University, Fort Collins 80523.
authors.forename: O
authors.initials: O
authors.lastname: Einarsdóttir
authors.forename: W S
authors.initials: WS
authors.lastname: Caughey
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D002417:Cattle; D003576:Electron Transport Complex IV / Q000378:metabolism*; D008024:Ligands; D009206:Myocardium / Q000201:enzymology*; D009609:Nitrous Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011485:Protein Binding; D011487:Protein Conformation; D013053:Spectrophotometry
chemical_list: D008024:Ligands; D002248:Carbon Monoxide; D003576:Electron Transport Complex IV; D009609:Nitrous Oxide