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

Nitric oxide ((NO)-N-center dot) 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)-N-center dot concentration and remains constant as long as (NO)-N-center dot 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)-N-center dot behave as two substrates of Cox, which promotes their oxidation with molecular oxygen as a co-substrate. In the presence of (NO)-N-center dot, Cox exhibits the property of switching from cyto-c oxidase to (NO)-N-center dot oxidase activity. With an "all or nothing" process Cox becomes an efficient (NO)-N-center dot 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)-N-center dot on the ischaemic-reperfusion injury. (C) 2009 Elsevier Inc. All rights reserved.