Respiratory control depression by tetraalkylammonium bromides in rat liver mitochondria

Six different lipophilic (hydrophobic) organic cations, tetraethyl-, tetrapropyl, tetrabutyl-, tetrapentyl-, tetrahexyl-, and tetraheptylammonium bromide, depressed respiratory control in rat liver mitochondria. Evaluation of mitochondrial responses in terms of a quadratic equation in log P (an index of lipophilicity) indicated that the NADH dehydrogenase receptor site for inhibitor (diminution of control of glutamate, alpha-ketoglutarate, and beta-hydroxybutyrate respiration) was more lipophilic than receptor sites for flavin-linked substrates (reduction of control of succinate, choline and alpha-glycerophosphate respiration). The succinate dehydrogenase receptor site for inhibition by the tetraalkylammonium bromides was more hydrophillic (less lipophilic) than the choline or alpha-glycerophosphate dehydrogenase receptor sites. Depression of respiratory control may be a function of charge density and of lipophilicity at specific inner membranal sites and the susceptible site may differ for different respiratory substrates.