Mode of inhibition of mitochondrial energy transduction by chlorophenoxyisobutyrate

Panini, SR and Kurup, CK Ramakrishna (1974) Mode of inhibition of mitochondrial energy transduction by chlorophenoxyisobutyrate. In: Biochemical Journal, 142 (2). pp. 253-261.

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Abstract

1. a-p-Chlorophenoxyisobutyric acid, the ethyl ester of which is widely used as an antihypercholesterolaemic drug, is an inhibitor of energy-transfer reactions in isolated rat liver mitochondria. 2. The compound at lower concentrations (<4.0mmol/mg of mitochondrial protein) inhibits state 3 oxidation, stimulates state 4 oxidation, abolishes respiratory control and stimulates the latent adenosine triphosphatase activity of mitochondria. The inhibition imposed on state 3 oxidation is relieved by dinitrophenol. 3. At higher concentrations it inhibits coupled phosphorylation as well as dinitrophenol-stimulated adenosine triphosphatase activity. The inhibition of state 3 oxidation under these conditions is not reversed by uncouplers. 4. The three coupling sites of phosphorylation exhibit differential susceptibility to inactivation by this compound. Coupled phosphorylation at the first site is abolished at a drug concentration of 3.0mmol/mg of protein. The third site is inactivated when the concentration of the drug reaches 5.0mmol/mg of protein. The second site is the most refractory and drug concentrations of the order of 10.0mmol/mg of protein are required effectively to inhibit phosphorylation at this site. 5. The compound also inhibits ATP-dependent reversal of electron transport as well as the adenosine triphosphatase activity in submitochondrial particles. 6. The oxidation of NADH and succinate in these particles is not inhibited. 7. These properties indicate that the compound acts as an `inhibitory uncoupler' of energy-transfer reactions in isolated mitochondria.

Item Type:	Journal Article
Publication:	Biochemical Journal
Publisher:	Portland Press
Additional Information:	Copyright of this article belongs to Portland Press.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	21 Dec 2009 10:39
Last Modified:	19 Sep 2010 05:44
URI:	http://eprints.iisc.ac.in/id/eprint/23162

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