Hydrophobic sites of the mitochondrial electron transfer system

Summary

Various classes of hydrophobic organic compounds of the aliphatic and aromatic series specifically inhibit electron transfer in the respiratory chain between NAD and cytochromeb. In liver mitochondria this effect can be reversed by vitamin K₃. There is a quantitative correlation between the inhibitory activity of these compounds and the value of their partition coefficients in octanol-water.

By measuring the effect of the inhibitors on the surface tension at the heptane-water interphase, it has been shown that the concentrations of hydrophobic inhibitors in the water phase required to fill 50% of the interphase boundary area are very close to the concentrations of these substances which decrease the rate of mitochondrial respiration by 50%. The conclusion is drawn that the region of the NADH dehydrogenase which binds these inhibitors resembles, in its adsorbtional properties, the hydrocarbon-water interphase.

Anions of carboxylic acids and phenols with pK_a<7.7 inhibit the respiratory chain before, and not after, NADH. Their effect is not reversed by vitamin K₃. In this case, again, the efficiency of the inhibitor depends upon their lipid solubility.

The fact that electroneutral hydrophobic compounds inhibit the respiratory chain NADH dehydrogenase, whereas charged ones do not, is discussed in connection with the mechanism of action of this enzyme. It is proposed that, after reduction, the negatively charged carrier dissociates from the hydrophobic region of the enzyme.