Abstract
1. 30mmum-4,5,6,7-Tetrachloro-2-trifluoromethylbenzimidazole (TTFB) uncouples respiratory-chain phosphorylation. The respiration rate of uncoupled mitochondria is significantly greater than the state 3 rate. Neither added orthophosphate nor ATP is required to sustain this rate. The oligomycin- and octylguanidine-induced inhibitions of respiration are relieved by uncoupling concentrations of TTFB. 2. Uncoupling concentrations of TTFB elicit a high adenosinetriphosphatase activity and inhibit the ATP-dependent succinate-linked reduction of NAD catalysed by submitochondrial particles from ox-heart mitochondria. 3. The action of TTFB is similar to that of 2,4-dinitrophenol. Evidence is presented which shows that it is the anionic forms of benzimidazoles and imidazoles, having the negative charge localized on the ring nitrogen atom, which are the effective uncoupling agents.
MeSH Terms
Adenosine Triphosphatases/metabolism
Animals
Antimetabolites/pharmacology
Benzimidazoles/pharmacology
Cattle
Chromatography, Thin Layer
Guanidines/pharmacology
In Vitro Techniques
Manometry
Mitochondria/enzymology,metabolism
Myocardium/cytology
Oligomycins/pharmacology
Oxidative Phosphorylation/drug effects
Rats
Chemicals
Antimetabolites
Benzimidazoles
Guanidines
Oligomycins
Adenosine Triphosphatases
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Beechey R B
References (18)
18 references, click to expand
-
A simple and rapid assay of oxidative phosphorylation.
Nature. 1955 Jun 25;175(4469):1120-1
PMID: 14394122
-
THE ANTIBACTERIAL ACTIVITY OF SOME FLUORINE-CONTAINING BENZIMIDAZOLES.
Biochem Pharmacol. 1964 May;13:751-4
PMID: 14181278
-
Antibiotics as tools for metabolic studies. I. A survey of toxic antibiotics in respiratory, phosphorylative and glycolytic systems.
Arch Biochem Biophys. 1958 Dec;78(2):587-97
PMID: 13618041
-
Inhibition of influenza virus multiplication by alkyl derivatives of benzimidazole. III. Relationship between inhibitory activity and chemical structure.
J Exp Med. 1953 Sep;98(3):245-59
PMID: 13084843
-
EFFECT OF IMIDAZOLE ON ADENOSINE TRIPHOSPHATASE, ADENOSINE TRIPHOSPHATE-INORGANIC PHOSPHATE EXCHANGE REACTION AND OXIDATIVE PHOSPHORYLATION.
Biochim Biophys Acta. 1964 Mar 9;81:587-90
PMID: 14170329
-
New antimetabolites of vitamin B12.
Nature. 1959 Oct 31;184:1383-4
PMID: 13838444
-
The effect of 5,6-dimethylbenzimidazole and related compounds on the growth of Lactobacillus lactis Dorner.
J Bacteriol. 1951 Nov;62(5):633-8
PMID: 14897840
-
ON THE MECHANISM OF OXIDATIVE PHOSPHORYLATION. VII. THE ENERGY-REQUIRING REDUCTION OF PYRIDINE NUCLEOTIDE BY SUCCINATE AND THE ENERGY-YIELDING OXIDATION OF REDUCED PYRIDINE NUCLEOTIDE BY FUMARATE.
Biochemistry. 1963 May-Jun;2:523-8
PMID: 14069541
-
Lipid solubility as a factor influencing the activity of uncoupling phenols.
Biochim Biophys Acta. 1962 Sep 10;63:46-54
PMID: 13953668
-
On the reduction of externally added DPN by succinate in submitochondrial particles.
Biochem Biophys Res Commun. 1961 Jun 28;5:231-7
PMID: 13763797
-
IMIDAZOLE INHIBITION OF THE ENERGY-LINKED REDUCTION OF NAD+ BY SUCCINATE.
Biochim Biophys Acta. 1964 Mar 9;81:585-7
PMID: 14170328
-
The effects of 2,4-dinitrophenol on mitochondrial oxidations.
Biochem J. 1964 Feb;90(2):237-48
PMID: 5890939
-
The influence of chemicals on the propagation of poliomyelitis virus in tissue culture.
J Immunol. 1952 Oct;69(4):441-50
PMID: 13000154
-
PROTEIN AS THE MITOCHONDRIAL SITE FOR ACTION OF UNCOUPLING PHENOLS.
Science. 1964 Aug 21;145(3634):824-6
PMID: 14163325
-
The oxidation of citrate, isocitrate and cis-aconitate by isolated mitochondria.
Biochem J. 1964 Feb;90(2):225-37
PMID: 4378636
-
A METHOD FOR THE COLORIMETRIC DETERMINATION OF PHOSPHORUS.
Science. 1944 Nov 3;100(2601):413-4
PMID: 17799462
-
Effect of nitrophenols and halogenophenols on the enzymic activity of rat-liver mitochondria.
Biochem J. 1958 Jun;69(2):306-11
PMID: 13546181
-
Growth inhibitors and their antagonists as mutagens and antimutagens in Escherichia coli.
J Gen Microbiol. 1958 Jun;18(3):543-64
PMID: 13549686