Inhibitor of electron

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. 

FIGURE 19-6 Method for determining the sequence of electron carriers. This method measures the effects of inhibitors of electron transfer on the oxidation state of each carrier. In the presence of an electron donor and 02/ each inhibitor causes a characteristic pattern of oxidized/reduced carriers those before the block become reduced (blue), and those after the block become oxidized (pink). 

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. 

Electron Flow through Photosystems I and II Predict how an inhibitor of electron passage through pheophytin would affect electron flow through (a) photosystem II and (b) photosystem I. Explain your reasoning. 

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. 

Meinhardt, S. W., and Crofts, A. R., 1982, The site and mechanism of action of myxothiazol as an inhibitor of electron transfer in Rhodopseudomonas sphaeroides, FEBS Lett. 149 217n222. 

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.

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. 

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.

---