Electron transport uncouplers

Liver mitochondria of vitamin E-deficient rabbit Increased TBA reactants Increased TBA, absorption 0, Severe destruction of enzymes and cytochromes of electron transport Uncoupling of oxidative phos-phorydation metabolic declinei swelling of mitochondria... 

Different light-induced A P values were observed in R.rubrum chromatophores by different methods ranging from 60 to 110 mV [see ref.10]. There are no data on AV generated by Rps.vlridls chromatophores in the literature. The light-induced membrane potential were sensitive to inhibitors of the cyclic electron transport uncouplers and also Orthophenanthroline an electron transport inhibitor of the reaction center (not shown). 

Uncouplers Disrupt the Coupling of Electron Transport and ATP Synthase... 

Many inhibitors of substrate oxidations, substrate transport, electron transport, and ATP synthesis are known including many well-known toxins (see Sherratt, 1981 Harold, 1986 Nicholls and Ferguson, 1992). These are not discussed here except to mention specific uncouplers of oxidative phosphorylation. Classic uncouplers such as 2,4-dinitrophenol have protonated and unprotonated forms, both of which are lipid soluble and cross the inner mitochondrial membrane discharging the proton gradient. This prevents ATP synthesis and stimulates respiration. 

Uncouplers of oxidative phosphorylation Compounds that uncouple oxidative phosphorylatiou from electron transport in the inner mitochondrial membrane. Most are weak lipophilic acids that can run down the proton gradient across this membrane. 

Carbonylcyanide-4-trilluoromethoxyphenylhydrazone is known as a protonophore or uncoupler of oxidative phosphorylation in bioelectrochemistry because it disrupts the tight coupling between electron transport and the ATP synthase. Uncouplers act by dis-... 

It was also observed in earlier studies that mitochondria not only accumulate Ca2+ as an alternative to phosphorylation of ADP (Ca2+ uptake uncouples phosphorylation from electron transport), but could also accumulate much larger amounts of Ca2+ if phosphate was also taken up, resulting in precipitation of Ca2+ within the matrix as insoluble hydroxyapatite, visible as electron-dense granules by EM. An unusual feature of these hydroxyapatite deposits is that they fail to become crystalline and remain amorphous even over protracted periods of time. Their presence in mitochondria in a number of disease conditions underlines the role for mitochondria as a sort of safety device, which can enable the cell to survive, if only for a limited period of time, situations of cytoplasmic Ca2+ overload. 

Oxidative phosphorylation DNP, potassium cyanide Antimycin A Sodium azide Formaldehyde Uncouples the oxidative phosphorylation from electron transport Acts at cytochrome oxidase B 7 Decreases the mitochondrial membrane potential 105 101,102 93,101,102... 

Dinitrophenol (1 mM) and potassium cyanide (KCN) (5 mM) are used as uncouplers of oxidative phosphorylation from electron transport (105). 

Toxicology. 2,4-Dinitrophenol (2,4-DNP) uncouples oxidative phosphorylation from electron transport, resulting in diminished production of ATP, with the energy dissipated as heat, which can lead to fatal hyperthermia. ... 

III (column 3 versus column 5), inhibition of the uncoupled electron transport rate was only partially relieved. Thus, the compounds appear to have two effects (a) the more sensitive is an effect on the ATP-generatlng pathway and (b) a second, but weaker, effect involved the electron-transport pathway. 

Chloroplasts, of Coupled Electron Transport and Phosphorylation, and of Uncoupled Electron Transport by Spinach Thylakoids... 

Figure 1. Representative polarographic traces that depict inhibition by energy transfer inhibitors and allelochemicals of ADP-stimulated electron transport in isolated spinach thylakoids and circumvention of the inhibition by an uncoupler (FCCP, 2 pM). Trace A chlorotributyltin (TBT, 1 pM) trace B phlorizin (400 pM) trace C DCCD (20 pM) trace D quercetin (200 pM) trace E naringenin (1 mM). Water served as electron donor and methyl viologen as electron acceptor. Rates of oxygen utilization, that resulted from the autooxidation of methyl viologen, expressed as pmol 0 consumed/mg Chi h, are indicated parenthet ically.

In the studies with Isolated chloroplasts and thylakolds, the primary effect of the phenolic allelochemlcals was on the ATP-generating pathway, i.e., energy transfer inhibition. The compounds acted on the electron-transport pathway at higher concentrations, but the exact slte(s) remain to be identified. These may be located on the oxidizing side of PS II or around the PQ pool. The sites are not associated with PS I. The compounds did not act as uncouplers. 

In mitochondria, the allelochemlcals acted primarily as electron transport inhibitors. Malate oxidation was more sensitive than either succinate or NADH oxidation. No evidence for interaction with a specific membrane complex was obtained. Instead, Inhibition of substrate oxidation seems to result from alterations and perturbations produced in the inner membrane as reflected in interference with the behavior of transport processes. The compounds did not act as uncouplers or directly inhibit ATP synthesis. However, naringenin, some of the flavones, and the cinnamic acids dj inhibit the hydrolysis of ATP catalyzed by mitochondrial Mg -ATPase. 

Much progress has been made in understanding the different mechanisms that can cause mitochondrial dysfunction, such as (i) uncoupling of electron transport from ATP synthesis by undermining integrity of inner membrane (ii) direct inhibition of electron transport system components (iii) opening of the mitochondrial permeability transition pore leading to irreversible collapse of the transmembrane potential and release of pro-apoptotic factors (iv) inhibition of the... 

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