Inhibitor of electron transport

FIGURE 21.29 The structures of several inhibitors of electron transport and oxidative phosphorylation. 

It is important that mitochondrial oxygen radical production depends on the type of mitochondria. Recently, Michelakis et al. [78] demonstrated that hypoxia and the proximal inhibitors of electron transport chain (rotenone and antimycin) decreased mitochondrial oxygen radical production by pulmonary arteries and enhanced it in renal arteries. This difference is probably explained by a lower expression of the proximal components of electron transport chain and a greater expression of mitochondrial MnSOD in pulmonary arteries compared to renal arteries. 

Site-specific inhibitors of electron transport shown using a mechanical model for the coupling of oxidation-reduction reactions. [Note Figure illustrates normal direction of electron flow.]... 

Site-specific inhibitors Site-specific inhibitors of electron transport have been identified and are illustrated in Figure 6.10. These compounds prevent the passage of electrons by binding to a component of the chain, blocking the oxidation/reduction reaction. Therefore, all electron carriers before the block are fully reduced, whereas those located after the block are oxidized. [Note Because electron transport and oxidative phosphorylation are tightly coupled, site-specific inhibition of the electron transport chain also inhibits ATP synthesis.]... 

Boydston, R., Paxton, J.D., Koeppe, D.E. Glyceollin a site-specific inhibitor of electron transport in isolated soyabean mitochondria. Plant Physiol 1983 72 151-155. 

Inhibitors of electron transport Rotenone Complex I Fish poison, insecticide... 

The absence of ADP is acting, in effect, as an inhibitor of electron transport, for reasons discussed in Prob. 14.6 below. Hence, by application of the crossover theorem (Chap. 10), there are large differences in the reduction of sites of the electron-transport-chain between NAD and coenzyme Q, between cytochrome b and cytochrome c, and between cytochrome c and cytochrome a. Therefore, the absence of ADP must be inhibiting electron transport at these points in fact, these are the sites of proton extrusion leading to ATP synthesis during electron transport. 

Oxidative phosphorylation is susceptible to inhibition at all stages of the process. Specific inhibitors of electron transport were invaluable in revealing the sequence of electron carriers in the respiratory chain. For example, rotenone and amytal block electron transfer in NADH-Q oxidoreductase and thereby prevent the utilization of NADH as a substrate (Figure 18.43). In contrast, electron flow resulting from the oxidation of succinate is unimpaired, because these electrons enter through QH2, beyond the block. AntimycinA interferes with electron flow from cytochrome h Q-cytochrome c... 

Figure 18.43. Sites of Action of Some Inhibitors of Electron Transport.

Chloroplasts both from pea leaves and the alga Acetabularia mediterranea show light-induced PPj synthesis which is stimulated if ADP is omitted from the reaction medium. The pea chloroplasts also show increased rates of PP synthesis in CF,-depleted chloroplasts. Furthermore, inhibitors of electron transport and energy transduction inhibit the PP synthesis [21]. 

Stigmatellin A is a powerful inhibitor of electron transport in mitochondria and chloroplasts. During the diastereo- and enantioselective total synthesis of this important natural product, D. Enders et al. utilized the Baker-Venkataraman rearrangement for the construction of the chromone system in good yield. ... 

Figure 18.43 Sites of action of some inhibitors of electron transport.

Inhibitors of electron transport cause the electron carriers between the source of electrons (e.g., NADH, FADH2) and the point of inhibition to become more reduced while the electron carriers between the point of inhibition and O2 become more oxidized. Thus there is a crossover point from reduced carriers to oxidized carriers. Therefore, from the information given we conclude that the inhibitor acts somewhere between QH2 and cytochrome c it prevents the reduction of cytochrome c by QH2. 

Fig. 10-13 Inhibitors of electron transport. (A) Rotenone and barbituric acid (B) 2-thenoylfluoroacetone and methylene blue (C) antimycin A and (D) cyanide, azide, carbon monoxide, and hydrogen sulfide.

Figure 1. Molecule discovered as an inhibitor of electron transport using beef heart mitochondria.

For the acaricide fenazaquin [4-(4-tert-butylphenethoxy)quinazoline], a potent inhibitor of electron transport at complex I (see Section 28.1.3), an additional low-affinity binding site in the stalk region of ATP synthase has been recently identified. The relevance of this newly discovered binding site is unknown since the enzymatic activity of ATP synthase is not impaired [12]. 

Heinen, W. (1972) Inhibitors of electron transport and oxidative phosphorylation, in Methods in Microbiology (eds J. R. Norris and D. W. Ribbons), Academic Press, London. 

Fig. 1 Effect of various agents on the phosphorylation of the B875 complex in chromatophores. Phosphorylation in the presence of (a) 40)LtM DCCD (N,N -Dicyclohexylcarbodiimide, inhibitor of the membrane-bound ATP-ase), (b) 40/im DCCD, (c) 1/iM antimycin A (an inhibitor of electron flow between cytochrome b and cytochrome cl), (d) 100IM antimycin A, (e) 100/iM DBMIB, (f) 5mM Na-ascorbate (a reductant), (g) 5mM Na-dithionite (a strong reductant) and (h) 5mM potassium ferricyanide (an oxidant and inhibitor of electron transport at the reaction center). All samples except (a) contained 2jL6g/ml venturicidin.

Much of our knowledge of the processes involved in electron transport and oxidative phosphorylation has come from studies using inhibitors. Figure 3.26 shows the oxygen electrode traces from mitochondria incubated with malate and an inhibitor of electron transport, with or without the addition of dinitrophenol as an uncoupler. Inhibitors of electron transport include ... 

Figure 3.26 Oxygen consumption by mitochondria incubated with malate and ADP, plus an inhibitor of electron transport, with and without an uncoupler.

The simulation program Oxygen Electrode on the CD permits you to perform experiments on mitochondria incubated with malate or succinate, using varying concentrations of ADP, with and without inhibitors of electron transport, oligomycin and an uncoupler. 

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