Nadh

NAD+

Intermembrane space (p side)

Intermembrane space (p side)

Matrix (n side)

NAD+

Matrix (n side)

Membrane arm

FIGURE 19-9 NADH:ubiquinone oxidoreductase (Complex I). Complex I catalyzes the transfer of a hydride ion from NADH to FMN, from which two electrons pass through a series of Fe-S centers to the iron-sulfur protein N-2 in the matrix arm of the complex. Electron transfer from N-2 to ubiquinone on the membrane arm forms QH2, which diffuses into the lipid bilayer. This electron transfer also drives the expulsion from the matrix of four protons per pair of electrons. The detailed mechanism that couples electron and proton transfer in Complex I is not yet known, but probably involves a Q cycle similar to that in Complex III in which QH2 participates twice per electron pair (see Fig. 19-12). Proton flux produces an electrochemical potential across the inner mitochondrial membrane (N side negative, P side positive), which conserves some of the energy released by the electron-transfer reactions. This electrochemical potential drives ATP synthesis.

Amytal (a barbiturate drug), rotenone (a plant product commonly used as an insecticide), and piericidin A (an antibiotic) inhibit electron flow from the Fe-S centers of Complex I to ubiquinone (Table 19-4) and therefore block the overall process of oxidative phosphorylation.

Ubiquinol (QH2, the fully reduced form; Fig. 19-2) diffuses in the inner mitochondrial membrane from Complex I to Complex III, where it is oxidized to Q in a process that also involves the outward movement of H+.

Complex II: Succinate to Ubiquinone We encountered Complex II in Chapter 16 as succinate dehydroge-

nase, the only membrane-bound enzyme in the citric acid cycle (p. 612). Although smaller and simpler than Complex I, it contains five prosthetic groups of two types and four different protein subunits (Fig. 19-10). Subunits C and D are integral membrane proteins, each with three transmembrane helices. They contain a heme group, heme b, and a binding site for ubiquinone, the final electron acceptor in the reaction catalyzed by Complex II. Subunits A and B extend into the matrix (or the cytosol of a bacterium); they contain three 2Fe-2S centers, bound FAD, and a binding site for the substrate, succinate. The path of electron transfer from the succinate-binding site to FAD, then through the Fe-S centers to the Q-binding site, is more than 40 A long, but none of the individual electron-transfer distances exceeds about 11 A—a reasonable distance for rapid electron transfer (Fig. 19-10).

TABLE 19-4 Agents That Interfere with Oxidative

Type of interference Compound*

Phosphorylation or Photophosphorylation

Target/mode of action

Inhibition of electron transfer

Inhibition of ATP synthase

Uncoupling of phosphorylation from electron transfer

Cyanide

Carbon monoxide

Antimycin A

Myxothiazol

Rotenone

Amytal

Piericidin A

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