Uncouplers of rat-liver mitochondrial oxidative phosphorylation

Abstract

1. The ability of a series of compounds to uncouple oxidative phosphorylation of rat-liver mitochondria has been investigated. 2. The compounds were: 2-amino-1,1,3-tricyanopropene; carbonyl cyanide phenylhydrazone and its m-chloro and p-trifluoromethoxy derivatives; 4,5,6,7-tetrachloro-, 5-chloro-4-nitro-, 5-nitro-and 4,5,6,7-tetrachloro-1-methyl-benzotriazole; 4-hydroxy-3,5-di-iodo-, 3,5-di-bromo-4-hydroxy- and 3,5-dichloro-4-hydroxy-benzonitrile; and pentafluorophenol. 3. In a medium the components and physical condition of which were, as far as possible, kept constant, each compound was tested for ability to stimulate adenosine triphosphatase, to stimulate respiration in the presence of pyruvate as substrate, to inhibit phosphate uptake and to prevent swelling by trimethyltin. 4. Each compound was also examined with respect to its ability to produce rapid rigor mortis in mice. 5. The biological properties were compared with the dissociation constant and the hexane-water partition coefficient for each compound. 6. With the exception of 4,5,6,7-tetrachloro-1-methylbenzotriazole, all the compounds behaved qualitatively as 2,4-dinitrophenol. 7. Within each class of compound there is a relation between biological activity and the physical attributes measured. 8. The most efficient uncouplers were the most acidic and the most hydrophobic.

Adenosine Triphosphatase Activity Associated with Mung Bean Mitochondria

“…The results presented in Figure 3 suggest that stimulation of state 4 respiration, ATPase stimulation, and inhibition of phosphate uptake by DNP were mediated through a common site. Similar curves for DNP have been obtained in studies with intact rat liver mitochondria (1,19).…”

Properties of Higher Plant Mitochondria. II. Effects of DNP, m-Cl-CCP, and Oligomycin on Respiration of Mung Bean Mitochondria

“…Thle action of an uncoupling agent thus appears to depend on the kind of substrate used in the experiment. These results do not support Parker's view that all uncouplers produce their effects by a similar mechanism (23). Table I summarizes the results from mung bean mitochondria and compares them with the data from rat liver mitochondria.…”

“…The concentration of DNP or mii-Cl-CCP which inhibits oxidative phosphorylation is capable of stimulating iboth latent ATPase activity and respiratory rate of mitochondria (8,11,12,19,(21)(22)(23). Furthermore, a current hypothesis is that the primary action of these uncoupling agents is to hydrolyze "highenergy intermediates" which are formed during oxidative phosphorylation (4-7, 19, 20, 22, 23).…”

“…Of the 2 uncoupling agents tested, malate oxidation consistently required 1.5 to 2 times higher concentration of the agents for the half-maximal effects than succinate oxidation. From The classical paper of Loomiiis and Lipmann (21), has been followed by a nunliber of papers showing that DNP3 uncouples phosphorvlation from oxidation in mitochondria isolated both from planlt tissues (1,2,9,10,15,25,26) and from animal tissues (3,4,7, 13,19,23,24). The uncoupling concentration of DNP is between 10-5 andl 10-4 m. Recently.…”

Anti-Inflammatory Properties of N-Phenylanthranilic Acid Derivatives in Relation to Uncoupling of Oxidative Phosphorylation

“…In studies on the uncoupling activities of phenols, carbonyl cyanide phenylhydrazones and benzotriazoles, it has been found that more acidic and more lipophilic compounds generally show higher uncoupling activities than those of less acidic and less lipophilic compounds (27)(28)(29)(30). Of the compounds tested in the present experiments, those which showed potent uncoupling activities were more lipophilic, except for 3-benzoyl-PAA.…”