Nitric oxide ejects electrons from the binuclear centre of cytochrome c oxidase by reacting with oxidised copper: A general mechanism for the interaction of copper proteins with nitric oxide?

Small increases in NO concentration can inhibit mitochondrial oxygen consumption by reacting at the binuclear haem a₃/Cu(B) oxygen reduction site of cytochrome c oxidase. Here we demonstrate that under normal turnover conditions NO reacts initially with the oxidised Cu(B) rather than the haem as We propose that hydration of an initial Cu⁺/NO⁺ complex forms nitrite, a proton and Cu(B); the latter ejects an electron from the binuclear centre and results in the observed (100 s^-1) reduction of other electron transfer centres in the enzyme (haem a and Cu(A)) These reactions may have implications for the interactions of NO with other topper proteins.