Electron transport system inhibitors

Attention has been directed to the dechlorination of polychlorinated benzenes by strains that use them as an energy source by dehalorespiration. Investigations using Dahalococcoides sp. strain CBDBl have shown its ability to dechlorinate congeners with three or more chlorine substituents (Holscher et al. 2003). Although there are minor pathways, the major one for hexachlorobenzene was successive reductive dechlorination to pentachlorobenzene, 1,2,4,5-tetrachlorobenzene, 1,2,4-trichlorobenzene, and 1,4-dichlorobenzene (Jayachandran et al. 2003). The electron transport system has been examined by the use of specific inhibitors. lonophores had no effect on dechlorination, whereas the ATP-synthase inhibitor A,A -dicyclohexylcarbodiimide (DCCD) was strongly inhibitory (Jayachandran et al. 2004). 

Figure 1. The channels which can be available for proton release in different cells. These may be activated by ligands attached to receptors or signals generated by the electron transport system. The electron transport across the membrane can also be accompanied by proton movement, depending on the orientation of electron transport, but th is movement would be I imited because of the slow rate of electron transport compared to the rapid rate which can be elicited through channels. Any possible relation of oxidase control to the H+-ATPase or the H -K+-ATPase has not been tested by inhibitors such as bafilomycin or omeprazole, respectively (Swallow et al., 1990).

Detection of the components of an electron transport system, involving cytochromes, is based on (a) identification of the various cytochromes by absorption and difference spectroscopy at room and liquid-nitrogen temperatures, and (b) the use of specific inhibitors, such as antimycin A and cyanide, for the various... 

The following tables describe four series of assays. Series I and II characterize the substrate specificity of Keilin-Hartree particles, whereas Series III and IV employ the autoxidizable dye, methylene blue, and various inhibitors to characterize the electron-transport system in these particles. It may be practical to divide the class into groups that will only... 

Four electron carriers (A, B, C, and D) are required in the electron transport system of a recently discovered aerobic bacterium. You find that in the presence of substrate and 02, four inhibitors (I, II, III, and IV) block respiration at four different sites. From differential spectrophotometry of the electron carriers, you find that these inhibitors yield the patterns of oxidation state of the carriers shown below. What... 

Mitochondrial electron transport system Sulfuramid, chlorfenapyr Azocyclotin, cyhexatin, Fenbutatin-oxide, propargite, Tetradifon, diafenthiuron Uncouplers of oxidative phosphorylation Inhibitors of ATP synthase... 

Viologen dyes are potent inhibitors of methane formation in whole cells (6). Methane formation is inhibited by increasing concentrations of benzyl viologen, and if the culture of M. omelianskii is used, molecular hydrogen is evolved as methane formation is inhibited (Figure 1). To explain the effectiveness of such low concentration levels it is beheved that these dyes inhibit a specific site in the electron transport system by an irreversible reaction. 

The basis for this combination is two distinct and unrelated mechanisms of action against the parasite. Atovaquone is a selective inhibitor of the Plasnuidiiim s mitochondrial electron transport system, and cycloguanil is a dihydrofolatc reductase inhibitor. Atovaquone s chemistry is based on it... 

The initial sensors and subsequent signal transduction systems of hypoxic vasoconstriction (HPV) remain an area of intense investigation (21,22). At the cellular level, pulmonary artery smooth muscle (PASM) contraction depends on an increase in cytosolic calcium from the extracellular space as well as release from intracellular stores, and membrane depolarization due to closure of K+ channels. Many argue that the mitochondria is a primary oxygen sensor such that electron transport chain inhibitors can specifically inhibit HPV and/or prevent the hypoxia-specific response. Reactive oxygen species are also implicated in HPV. Two different models are proposed one describes an increase in mitochondrial ROS mediated via increased intracellular calcium release, and the second describes a decrease in mitochondrial ROS mediated via inhibition of the Kv channel (Figure 8.2). 

Electron-transport system. Both the hydrogen- and the electron-transport portion are presented. The P indicates steps that have a sufficient energy drop to produce a high-energy phosphate. The circled numbers indicate where corresponding inhibitors of the electron-transport system have their effect. 

The movement of electrons through the electron carrying proteins of the inner mitochondrial membrane is shown in Figure 15.9. Also shown are inhibitors of electron movement at their point of action and the sites where artificial electron acceptors can accept electrons from the electron transport system. Specific inhibitors shown in Figure 15.9 are rotenone, amytal, antimycin A, cyanide, azide, and carbon monoxide. The artificial electron acceptors are methylene blue, phenazine methosulfate, 2,6-indophenol, tetramethyl-p-phenylene diamine, and ferricyanide. 

Cyanide is a respiratory inhibitor that blocks electron transfer from cytochrome oxidase (Complex IV) to oxygen in the electron transport system (Figure 15.9). 

The egg and the embryonic cell are well endowed with bioenergetic pathways. The multiple-enzyme systems involved in glycolysis, the hexose monophosphate shunt, the Krebs cycle, the electron transport chain, and oxidative phosphorylation have all been found in the vertebrate embryo. In the embryonic and in the mature cell, oxidation through the Krebs cycle, electron transport, and coupling of oxidation and phosphorylation occur in mitochondria. The chemical energy provided by these pathways is needed for normal development because if either glycolysis, Krebs cycle, or electron transport chain inhibitors are administered in vivo or added to explanted chick or sea urchin embryos, embryonic development is arrested. 

Low concentrations of antimycin A were found in 1949 to inhibit almost completely the oxygen uptake of respiring yeasti29. Later it was shown that the antibiotic is a powerful inhibitor of succinoxidase. Chance and Willi-ams o have established that antimycin A inactivates a specific component of the electron transport system in mitochondria, with the result that reduced cytochrome b is not oxidised by cytochrome c. The antibiotic... 

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