Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Electron Transport, Oxidative Phosphorylation, and Regulation of ATP Synthesis
Electron carriers always operate in a specific sequence

What evidence indicates that electron carriers in the Respiratory Chain function in the precise sequence outlined above? First, their standard reduction potentials (Figs. 14-7 and 17-1) become progressively more positive as they approach oxygen, exactly as one would expect, since electrons spontaneously flow from electronegative to electropositive systems with a concomitant decrease in Free energy. Second, each link in this chain is specific for a particular electron donor and acceptor. And finally, structurally distinct complexes of functionally linked electron carriers have been successfully isolated from the mitochondrial membrane (Fig. 17-12).

Complex I consists of NADH dehydrogenase and its closely associated iron-sulfur centers. Complex II comprises succinate dehydrogenase and its iron-sulfur centers. Complex III contains Cytochromes b and c along with a specific iron-sulfur center. Complex IV is composed of cytochromes a and a₃. Ubiquinone acts as a mobile link between complexes I, II, and III, whereas cytochrome c bridges complexes III and IV (Fig. 17-12).

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Fig. 17-12. Electron-transporting complexes. These can be isolated as functional assemblies.

The Study of electron transport has been greatly facilitated by The Use of specific inhibitors that block specific steps in the process. Particularly valuable among these are: 1) rotenone, which blocks Electron transfer from NADH to ubiquinone (this highly toxic plant-derived compound was historically used by Native Americans as a fish poison); 2) antimycin A, a toxic antibiotic produced by a Streptomyces strain, which blocks electron flow from ubiquinone to cytochrome c; and 3) cyanide, one of the most potent poisons known, which blocks the oxygen-reduction process catalyzed by cytochrome aa₃ (Fig. 17-13). (Carbon monoxide is another important inhibitor of cytochrome aa₃.) When the Electron Transport Chain is inhibited at a specific point, a crossover point is established, as illustrated by the hydraulic model in Fig. 17-14. Electron carriers situated immediately before the block become more reduced, whereas those located after it become more oxidized. Such shifts can be readily detected spectrophotometrically because the oxidized and reduced forms of these carriers have distinct absorption spectra.

Fig. 17-13. Sites of action of various inhibitors that block electron transport. Amobarbital is a barbiturate drug used as a hypnotic. In addition to cyanide, powerful inhibitors of cytochrome oxidase include Carbon Monoxide and hydrogen sulfide.

Fig. 17-14. Hydraulic model of the respiratory chain. A. Under normal conditions, the respiratory chain maintains a steady state. The degree of reduction of successive electron carriers across a population of Cell/35.html">Mitochondria decreases as electrons pass from substrates to oxygen. B. The electron transport inhibitor antimycin A creates a crossover point in the respiratory chain where the oxidation-reduction state of the carriers changes abruptly.