Abstract
Abstract Twelve different lipophilic organic cations (tetraethyl-, tetrapropyl-, tetrabutyl-, tetrapentyl-, tetrahexyl-, tetraheptyl-, decyltrimethyl-, cetyltrimethyl-, and benzyltriethylammonium bromides; and dibenzyldimethylammonium chloride, N-1-dodecylnicotinamide chloride, and cetylpyridinium bromide) depressed respiratory control in rat liver mitochondria. Evaluation of mitochondrial responses in terms of linear free energy processes for the six symmetrical tetraalkylammonium bromides indicated that the NADH dehydrogenase receptor site for inhibitor (diminution of control of glutamate respiration) was more lipophilic than the succinate dehydrogenase receptor site (reduction of control of succinate respiration). (Both receptor activities have been located on the mitochondrial inner membrane by other workers.) Prior incubation of intact mitochondria with a tetraalkylammonium halide up to an hour at 30° did not alter the results. Depression of respiratory control by the symmetrical quaternary ammonium halides, e.g. tetrabutylammonium bromide, occurred by two different mechanisms depending upon inhibitor concentrations: (a) inhibition of phosphorylation at low concentrations of the alkyl bromide and (b) uncoupling of oxidative phosphorylation at high concentrations of the alkyl bromide. Depression of respiratory control by the nonsymmetrical organic cations occurred by either inhibition of electron transport, action as an inhibitor of phosphorylating oxidation, or as an uncoupler. The mechanism of inhibition was dependent upon the organic structure of these amphipathic molecules.
Highlights
Depression of respiratory control by the symmetrical quaternary ammonium halides, e.g. tetrabutylammonium bromide, occurred by two different mechanisms depending upon inhibitor concentrations: (a) inhibition of phosphorylation at low concentrations of the alkyl bromide and (b) uncoupling of oxidative phosphorylation at high concentrations of the alkyl bromide
Mitochondrial pellet was resuspendctl in the sucrose-ethylcncdiaminetetraacetic acid (EDTA) solution and used immediately
Albumin has been found to stabilize mitochondrial functions (5) and provide for greater rfficicncy of respiration coupled to phosphorylation (6)
Summary
Twelve different lipophilic organic cations (tetraethyl-, tetrapropyl-, tetrabutyl-, tetrapentyl-, tetrahexyl-, tetraheptyl-, decyltrimethyl-, cetyltrimethyl-, and benzyltriethylammonium bromides; and dibenzyldimethylammonium chloride, N-1-dodecylnicotinamide chloride, and cetylpyridinium bromide) depressed respiratory control in rat liver mitochondria. Depression of respiratory control by the symmetrical quaternary ammonium halides, e.g. tetrabutylammonium bromide, occurred by two different mechanisms depending upon inhibitor concentrations: (a) inhibition of phosphorylation at low concentrations of the alkyl bromide and (b) uncoupling of oxidative phosphorylation at high concentrations of the alkyl bromide. The potency of the detergents for both depression of respiratory control and inhibition of energized recovery from swelling was a function of the number of methylene groups in the alkyl sulfate. This was equated with the lipophilicity log P (2, 7, 8) of the molecules as measured by their partitioning P across the interfacial barrier of l-octanol and water.
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