On the mechanism of inhibition of NADH oxidase by ubiquinone-3.

The combined effects of rotenone and ubiquinone-3 on the kinetics of NADH dehydrogenase and NADH oxidase have been investigated. The two inhibitors do not show additivity; on the other hand, ubiquinone-3, when preincubated with the enzyme, partially removes rotenone sensitivity. The inhibition of NADH oxidase by ubiquinone-3 is the result of at least two combined effects: the competition of the less active ubiquinone-3 with endogenous ubiquinone-10 in the acceptor site of the dehydrogenase, and a nonspecific action on the structure of complex I. The latter effect is perhaps mediated by a physical change of the phospholipid bilayer similar to that observed with agents such as butanol, perturbing lipid-protein interactions in the membrane.