Interaction of nitric oxide with the activity of cytosolic NADH/cytochrome c electron transport system.

Nitric oxide ((.)NO) generated by the dissociation of S-nitrosoglutathione or added as gaseous solution, inhibits the oxidation of exogenous NADH supported by the activity of the cytosolic NADH/cyto-c electron transport pathway. The inhibition is immediate, very strong, higher at lower oxygen concentration, independent on the (.)NO concentration and remains constant as long as (.)NO is no more available and then is spontaneously removed. The data obtained, not in contrast with those reported with isolated cytochrome oxidase (Cox), strengthen a new concept: reduced cytochrome c (cyto-c) and (.)NO behave as two substrates of Cox, which promotes their oxidation with molecular oxygen as a co-substrate. In the presence of (.)NO, Cox exhibits the property of switching from cyto-c oxidase to (.)NO oxidase activity. With an "all or nothing" process Cox becomes an efficient (.)NO scavenger. The persistence of membrane potential, even in the presence of high inhibition of oxygen uptake, could be tentatively correlated to the protective effect of (.)NO on the ischaemic-reperfusion injury.