NADH dehydrogenase also contains peptide subunits with Fe-S centers (Fig. 6.9). At Complex I, electrons move from NADH to FMN to the iron of the Fe-S centers and then to CoQ. As electrons flow, they lose energy. This energy is used to pump four H+ across the inner mitochondrial membrane, from the matrix to the intermembrane space.
3.
Succinate dehydrogenase: At Complex II, electrons from the succinate dehydrogenase–catalyzed oxidation of succinate to fumarate move from the coenzyme, FADH2, to an Fe-S protein, and then to CoQ. [Note:
Because no energy is lost in this process, no H+ are pumped at Complex II.] 4.
Coenzyme Q: CoQ is a quinone derivative with a long, hydrophobic isoprenoid tail. It is made from an intermediate of cholesterol synthesis (see p. 221). [Note: It is also called ubiquinone because it is ubiquitous in biologic systems.] CoQ is a mobile electron carrier and can accept electrons from NADH dehydrogenase (Complex I), from succinate dehydrogenase (Complex II) and from other mitochondrial dehydrogenases, such as glycerol 3-phosphate dehydrogenase (see p.
80) and acyl CoA dehydrogenases (see p. 192). CoQ transfers electrons to Complex III (cytochrome bc1). Thus, a function of CoQ is to link the flavoprotein dehydrogenases to the cytochromes.
5.
Cytochromes: The remaining members of the ETC are cytochrome proteins. Each contains a heme group (a porphyrin ring plus iron). Unlike the heme groups of hemoglobin, the cytochrome iron is reversibly converted from its ferric (Fe3+) to its ferrous (Fe2+) form as a normal part of its function as an acceptor and donor of electrons. Electrons are passed along the chain from cytochrome bc1 (Complex III), to cytochrome c, and then to cytochromes a + a3 ([Complex IV] see Fig. 6.8). As electrons flow, four H+ are pumped across the inner mitochondrial membrane at Complex III and two at Complex IV. [Note: Cytochrome c is located in the intermembrane space, loosely associated with the outer face of the inner membrane. As seen with CoQ, cytochrome c is a mobile electron carrier.] 6.
Cytochrome a + a3: Because this cytochrome complex (Complex IV) is the only electron carrier in which the heme iron has an available coordination site that can react directly with O2, it also is called cytochrome c oxidase. At Complex IV, the transported electrons, O2, and free H+ are brought together, and O2 is reduced to H2O (see Fig. 6.8). [Note: Four electrons are required to reduce one molecule of O2 to two molecules of H2O.] Cytochrome c oxidase contains Cu atoms that are required for this complicated reaction to occur. Electrons move from CuA to cytochrome a to cytochrome a3 (in association with CuB) to O2.
7.
Site-specific inhibitors: Inhibitors of specific sites in the ETC have been identified and are illustrated in Figure 6.10. These respiratory inhibitors 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: Inhibition of the ETC inhibits ATP synthesis because these processes are tightly coupled (see p. 78).]
NaN3 = sodium azide.