Respiratory chain electron carriers

NAD+ and NADP+ are coenzymes of dehydrogenases. NADH and NADPH are intermediate carriers of both hydrogen and electrons. Most NAD-dependent enzymes are located in the mitochondria and deliver H2 to the respiratory chain whereas NADP-dependent enzymes take part in cytosolic syntheses (reductive biosyntheses). 

NADH and reduced substrate dehydrogenase-flavoproteins (FPH2) must be continually reoxidized for mitochondrial oxidations to proceed. This is achieved by the electron transport chain (respiratory chain) which is a series of redox carriers of graded redox potential in the inner mitochondrial membrane (Appendix 1) that catalyzes the net reactions ... 

The cytochromes are iron-containing hemoproteins in which the iron atom oscillates between Fe + and Fe + during oxidation and reduction. Except for cytochrome oxidase (previously described), they are classified as dehydrogenases. In the respiratory chain, they are involved as carriers of electrons from flavoproteins on the one hand to cytochrome oxidase on the other (Figure 12-4). Several identifiable cytochromes occur in the respiratory chain, ie, cytochromes b, Cp c, a, and (cytochrome oxidase). Cytochromes are also found in other locations, eg, the endoplasmic reticulum (cytochromes P450 and h, and in plant cells, bacteria, and yeasts. 

Ubiquinone, known also as coenzyme Q, plays a crucial role as a respiratory chain electron carrier transport in inner mitochondrial membranes. It exerts this function through its reversible reduction to semiquinone or to fully hydrogenated ubiquinol, accepting two protons and two electrons. Because it is a small lipophilic molecule, it is freely diffusable within the inner mitochondrial membrane. Ubiquinones also act as important lipophilic endogenous antioxidants and have other functions of great importance for cellular metabolism. ... 

Now, we may consider in detail the mechanism of oxygen radical production by mitochondria. There are definite thermodynamic conditions, which regulate one-electron transfer from the electron carriers of mitochondrial respiratory chain to dioxygen these components must have the one-electron reduction potentials more negative than that of dioxygen Eq( 02 /02]) = —0.16 V. As the reduction potentials of components of respiratory chain are changed from 0.320 to +0.380 V, it is obvious that various sources of superoxide production may exist in mitochondria. As already noted earlier, the two main sources of superoxide are present in Complexes I and III of the respiratory chain in both of them, the role of ubiquinone seems to be dominant. Although superoxide may be formed by the one-electron oxidation of ubisemiquinone radical anion (Reaction (1)) [10,22] or even neutral semiquinone radical [9], the efficiency of these ways of superoxide formation in mitochondria is doubtful. 

Ubiquinones (coenzymes Q) Q9 and Qi0 are essential cofactors (electron carriers) in the mitochondrial electron transport chain. They play a key role shuttling electrons from NADH and succinate dehydrogenases to the cytochrome b-c1 complex in the inner mitochondrial membrane. Ubiquinones are lipid-soluble compounds containing a redox active quinoid ring and a tail of 50 (Qio) or 45 (Q9) carbon atoms (Figure 29.10). The predominant ubiquinone in humans is Qio while in rodents it is Q9. Ubiquinones are especially abundant in the mitochondrial respiratory chain where their concentration is about 100 times higher than that of other electron carriers. Ubihydroquinone Q10 is also found in LDL where it supposedly exhibits the antioxidant activity (see Chapter 23). 

There are two kinds of redox interactions, in which ubiquinones can manifest their antioxidant activity the reactions with quinone and hydroquinone forms. It is assumed that the ubiquinone-ubisemiquinone pair (Figure 29.10) is an electron carrier in mitochondrial respiratory chain. There are numerous studies [235] suggesting that superoxide is formed during the one-electron oxidation of ubisemiquinones (Reaction (25)). As this reaction is a reversible one, its direction depends on one-electron reduction potentials of semiquinone and dioxygen. 

A naturally occurring phenazine of nonbacterial origin is the methano-phenazine (MP) (10) which has been isolated from the cytoplasmic membrane of Methanosarcina (Ms.) mazei Gol archaea. The structure, synthesis, properties, and function of this natural product will be discussed in detail since it is not only the first and so far the sole phenazine derivative from archaea, but also the first one that is acting as an electron carrier in a respiratory chain - a biologic function equivalent to that of ubiquinones in mitochondria and bacteria. 

In the third step, 1, -/3-hydroxyacyl-CoA is dehydrogenated to form /3-ketoacyl-CoA, by the action of /3-hydroxyacyl-CoA dehydrogenase NAD+ is the electron acceptor. This enzyme is absolutely specific for the l stereoisomer of hydroxyacyl-CoA The NADH formed in the reaction donates its electrons to NADH dehydrogenase, an electron carrier of the respiratory chain, and ATP is formed from ADP as the electrons pass to 02. The reaction catalyzed by /3-hydroxyacyl-CoA dehydrogenase is closely analogous to the malate dehydrogenase reaction of the citric acid cycle (p. XXX). 

NAD-linked dehydrogenases remove two hydrogen atoms from their substrates. One of these is transferred as a hydride ion ( II ) to NAD+ the other is released as H+ in the medium (see Fig. 13-15). NADH and NADPH are water-soluble electron carriers that associate reversibly with dehydrogenases. NADH carries electrons from catabolic reactions to their point of entry into the respiratory chain, the NADH dehydrogenase complex described below. NADPH generally supplies electrons to anabolic reactions. Cells maintain separate pools of NADPH and NADH, with different redox potentials. This is accomplished by holding the ratios of [reduced form]/[oxidized form] relatively high for NADPH and relatively low for NADH. Neither NADH nor NADPH can cross the inner mitochondrial membrane, but the electrons they carry can be shuttled across indirectly, as we shall see. 

In addition to NAD and flavoproteins, three other types of electron-carrying molecules function in the respiratory chain a hydrophobic quinone (ubiquinone) and two different types of iron-containing proteins (cytochromes and iron-sulfur proteins). Ubiquinone (also called coenzyme Q, or simply Q) is a lipid-soluble ben-zoquinone with a long isoprenoid side chain (Fig. 19-2). The closely related compounds plastoquinone (of plant chloroplasts) and menaquinone (of bacteria) play roles analogous to that of ubiquinone, carrying electrons in membrane-associated electron-transfer chains. Ubiquinone can accept one electron to become the semi-quinone radical ( QH) or two electrons to form ubiquinol (QH2) (Fig. 19-2) and, like flavoprotein carriers, it can act at the junction between a two-electron donor and a one-electron acceptor. Because ubiquinone is both small and hydrophobic, it is freely diffusible within the lipid bilayer of the inner mitochondrial membrane and can shuttle reducing equivalents between other, less mobile electron carriers in the membrane. And because it carries both electrons and protons, it plays a central role in coupling electron flow to proton movement. 

In the overall reaction catalyzed by the mitochondrial respiratory chain, electrons move from NADH, succinate, or some other primary electron donor through flavoproteins, ubiquinone, iron-sulfur proteins, and cytochromes, and finally to 02. A look at the methods used to determine the sequence in which the carriers act is instructive, as the same general approaches have been used to study other electron-transfer chains, such as those of chloroplasts. 

TABLE 19-2 Standard Reduction Potentials of Respiratory Chain and Related Electron Carriers... 

The electron carriers of the respiratory chain are organized into membrane-embedded supramolecular... 

The Q cycle accommodates the switch between the two-electron carrier ubiquinone and the one-electron carriers—cytochromes b562, b566, clt and c—and explains the measured stoichiometry of four protons translocated per pair of electrons passing through the Complex III to cytochrome c. Although the path of electrons through this segment of the respiratory chain is complicated, the net effect of the transfer is simple QH2 is oxidized to Q and two molecules of cytochrome c are reduced. 

FIGURE 19-15 Summary of the flow of electrons and protons through the four complexes of the respiratory chain. Electrons reach Q through Complexes I and II. QH2 serves as a mobile carrier of electrons and protons. It passes electrons to Complex III, which passes them to another mobile connecting link, cytochrome c. Complex IV... 

FIGURE 19-33 Bacterial respiratory chain, (a) Shown here are the respiratory carriers of the inner membrane of E. coli. Eubacteria contain a minimal form of Complex I, containing all the prosthetic groups normally associated with the mitochondrial complex but only 14 polypeptides. This plasma membrane complex transfers electrons from NADH to ubiquinone or to (b) menaquinone, the bacterial equivalent of ubiquinone, while pumping protons outward and creating an electrochemical potential that drives ATP synthesis. 

This hypothesis presumes that early free-living prokaryotes had the enzymatic machinery for oxidative phosphorylation and predicts that their modern prokaryotic descendants must have respiratory chains closely similar to those of modern eukaryotes. They do. Aerobic bacteria carry out NAD-linked electron transfer from substrates to 02, coupled to the phosphorylation of cytosolic ADP. The dehydrogenases are located in the bacterial cytosol and the respiratory chain in the plasma membrane. The electron carriers are similar to some mitochondrial electron carriers (Fig. 19-33). They translocate protons outward across the plasma membrane as electrons are transferred to 02. Bacteria such as Escherichia coli have F0Fi complexes in their plasma membranes the F portion protrudes into the cytosol and catalyzes ATP synthesis from ADP and P, as protons flow back into the cell through the proton channel of F0. 

Degree of Reduction of Electron Carriers in the Respiratory Chain The degree of reduction of each carrier... 

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