title: Nitric oxide and cytochrome oxidase: substrate, inhibitor or effector?
abstract: Endogenously produced nitric oxide (NO) controls oxygen consumption by inhibiting cytochrome c oxidase, the terminal electron acceptor of the mitochondrial electron transport chain. The oxygen-binding site of the enzyme is an iron/copper (haem a3/CuB) binuclear centre. At high substrate (ferrocytochrome c) concentrations, NO binds reversibly to the reduced iron in competition with oxygen. At low substrate concentrations, NO binds to the oxidized copper. Inhibition at the haem iron site is relieved by dissociation of the NO from the reduced iron. Inhibition at the copper site is relieved by oxidation of the bound NO and subsequent dissociation of nitrite from the enzyme. Therefore, NO can be a substrate, inhibitor or effector of cytochrome oxidase, depending on cellular conditions.
authors.affiliation: Dept of Biological Sciences, Central Campus, University of Essex, Wivenhoe Park, CO4 3SQ, Colchester, UK. ccooper@essex.ac.uk
authors.forename: Chris E
authors.initials: CE
authors.lastname: Cooper
mesh_terms: D003576:Electron Transport Complex IV / Q000378:metabolism*; D004791:Enzyme Inhibitors; D009569:Nitric Oxide / Q000502:physiology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D003576:Electron Transport Complex IV; D010100:Oxygen