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.
D000818:Animals; D002417:Cattle; D003579:Cytochrome Reductases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008563:Membrane Lipids / Q000502:physiology; D008929:Mitochondria, Heart / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010101:Oxygen Consumption / Q000187:drug effects; D012402:Rotenone / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D008563:Membrane Lipids; D009097:Multienzyme Complexes; D012402:Rotenone; D014451:Ubiquinone; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D003579:Cytochrome Reductases; D009245:NADH Dehydrogenase; C025204:Ubiquinone Q2