Reaction sites of rotenone, piericidin A, and amytal in relation to the nonheme iron components of NADH dehydrogenase.
The locus of inhibition of nicotinamide adenine dinucleotide, reduced form (NADH) oxidation in mitochondria by rotenone, piercidin A, and barbiturates is considered in the light of available information. Most lines of evidence indicate that the point of inhibition is on the O(2) side of NADH dehydrogenase. Kinetic experiments on the substrate-induced appearance of the electron paramagnetic resonance signal at g = 1.94 in membrane preparations (ETP) reveal that these inhibitors do not interfere with the reduction of the electron paramagnetic resonance detectable iron by NADH. Our spectrophotometric studies on complex I give no evidence for absorbance differences between untreated and rotenone or piericidin inhibited preparations, which can be attributed to nonheme iron. Whatever changes were observed appear to be due to cytochromes. These experiments, therefore, do not support the idea that in inhibited preparations electron transport is interrupted between the flavin and nonheme iron components of NADH dehydrogenase. The specific binding of rotenone and piericidin seems to involve both lipid and protein. The possibility that NADH dehydrogenase participates in the binding is suggested by the apparent stoichiometric relation between specific binding site titer and NADH dehydrogenase content and the profound effect of mersalyl inhibition of the enzyme on piericidin binding capacity.ETP, electron transport particle.
D000654:Amobarbital / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D007501:Iron / Q000494:pharmacology*; D009243:NAD; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D011725:Pyridines; D012402:Rotenone; D009243:NAD; D007501:Iron; D010088:Oxidoreductases; D000654:Amobarbital