Electron transport chain respiratory complexes

In contrast to common usage, the distinction between photosynthetic and respiratory Rieske proteins does not seem to make sense. The mitochondrial Rieske protein is closely related to that of photosynthetic purple bacteria, which represent the endosymbiotic ancestors of mitochondria (for a review, see also (99)). Moreover, during its evolution Rieske s protein appears to have existed prior to photosynthesis (100, 101), and the photosynthetic chain was probably built around a preexisting cytochrome be complex (99). The evolution of Rieske proteins from photosynthetic electron transport chains is therefore intricately intertwined with that of respiration, and a discussion of the photosynthetic representatives necessarily has to include excursions into nonphotosynthetic systems. 

Studies (see, e.g., (101)) indicate that photosynthesis originated after the development of respiratory electron transfer pathways (99, 143). The photosynthetic reaction center, in this scenario, would have been created in order to enhance the efficiency of the already existing electron transport chains, that is, by adding a light-driven cycle around the cytochrome be complex. The Rieske protein as the key subunit in cytochrome be complexes would in this picture have contributed the first iron-sulfur center involved in photosynthetic mechanisms (since on the basis of the present data, it seems likely to us that the first photosynthetic RC resembled RCII, i.e., was devoid of iron—sulfur clusters). 

Flutolanil is an inhibitor of succinate dehydrogenase complex (Complex II), in the mitochondrial respiratory electron transport chain. ... 

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). 

The inner mitochondrial membrane can be disrupted into five sepa rate enzyme complexes, called complexes I, II, III, IV, and V. Complexes I to IV each contain part of the electron transport chain (Figure 6.8), whereas complex V catalyzes ATP synthesis (see p. 78). Each complex accepts or donates electrons to relatively mobile electron carriers, such as coenzyme Q and cytochrome c. Each car rier in the electron transport chain can receive electrons from an electron donor, and can subsequently donate electrons to the next carrier in the chain. The electrons ultimately combine with oxygen and protons to form water. This requirement for oxygen makes the electron transport process the respiratory chain, which accounts for the greatest portion of the body s use of oxygen. 

The b cytochromes and cytochrome c, fit into this scheme between reducing substrates and cytochrome c. The idea thus developed that the respiratory apparatus includes a chain of cytochromes that operate in a defined sequence. The next question was whether the cytochromes are all bound together in a giant complex, or whether they diffuse independently in the membrane. Before we address this point, we need to consider three other types of electron carriers that participate in the electron-transport chain flavo-proteins, iron-sulfur proteins, and ubiquinone. 

Boxes indicate electron-transport chain complexes, whereas ovals represent the electron transporters UQ, RQ and cytochrome c. The open boxes represent complexes involved in the classical aerobic respiratory chain, whereas grey boxes represent complexes involved in malate dismutation. The vertical bar represents a scale for the standard redox potentials in mV. Translocation of protons by the complexes is indicated by H+ +. Abbreviations Cl, Clll and CIV, complexes I, III and IV of the respiratory chain cyt c, cytochrome c FRD, fumarate reductase Fum, fumarate SDH, succinate dehydrogenase Succ, succinate RQ, rhodoquinone UQ, ubiquinone. 

In juvenile liver fluke and miracidia, a respiratory chain up to cytochrome c oxidase is active and all evidence obtained so far indicates that in F. hepatica at least this electron-transport chain is not different from the classical one present in mammalian mitochondria (Figs 20.1 and 20.2). In the aerobically functioning stages, electrons are transferred from NADH and succinate to ubiquinone via complex I and II of the respiratory chain, respectively. Subsequently, these electrons are transferred from the formed ubiquinol to oxygen via the complexes III and IV of the respiratory chain. 

Fig. 5.2. Possible metabolic pathways in facultative anaerobic mitochondria. Shaded boxes show components of the electron-transport chain used during hypoxia, open boxes are components used during aerobiosis, and the hatched boxes (complex I and ATP-synthase) are components used under aerobic as well as anaerobic conditions. ASCT acetate succinate CoA-transferase, C cytochrome c, Cl, CIII and CIV complexes I, III and IV of the respiratory chain, CITR citrate, ECR enoyl-CoA reductase (such as present in Ascaris suum), ETF electron-transfer flavoprotein, ETF RQ OR electron-transfer flavoproteimrhodoquinone oxidoreductase, FRD fumarate reductase, FUM fumarate, MAE malate, OXAC oxaloacetate, PYR pyruvate, RQ rhodoquinone, SDH succinate dehydrogenase, SUCC succinate, Succ-CoA succinyl-CoA, TER trans-2-enoyl-CoA reductase (such as present in E. gracilis), UQ ubiquinone...

Fig. 5.3. The major components involved in mitochondrial NADH oxidation in facultative anaerobic mitochondria. In anaerobically functioning mitochondria, NADH is oxidized either by soluble enzymes (left) or by membrane-bound complexes of the electron-transport chain (middle). Under aerobic conditions, a classic respiratory chain is used to oxidize NADH (right). Proton translocation is indicated by H with arrows. Ovals represent the electron transporters RQ, UQ and cytochrome c (cyt. c), and electron transport is indicated by dashed arrows. The vertical bar represents a scale for the standard redox potentials in millivolts. Fum fumarate, NADH-DH NADH dehydrogenase, NADH-ECR soluble NADH enoyl-CoA reductase, RQH2 rhodoquinol, Succ succinate, UQH2 ubiquinol...

Most anaerobically functioning mitochondria use endogenously produced fumarate as a terminal electron-acceptor (see before) and thus contain a FRD as the final respiratory chain complex (Behm 1991). The reduction of fumarate is the reversal of succinate oxidation, a Krebs cycle reaction catalysed by succinate dehydrogenase (SDH), also known as complex II of the electron-transport chain (Fig. 5.3). The interconversion of succinate and fumarate is readily reversible by FRD and SDH complexes in vitro. However, under standard conditions in the cell, oxidation and reduction reactions preferentially occur when electrons are transferred to an acceptor with a higher standard redox potential therefore, electrons derived from the oxidation of succinate to fumarate (E° = + 30 mV) are transferred by SDH to ubiquinone,... 

SQR (respiratory complex II) is involved in aerobic metabolism as part of the citric acid cycle and of the aerobic respiratory chain (Saraste, 1999). QFR participates in anaerobic respiration with fumarate as the terminal electron acceptor (Kroger, 1978 Kroger etal., 2002) and is part of the electron transport chain catalyzing the oxidation ofvarious donor substrates (e.g., H2 or formate) by fumarate. These reactions are coupled via an electrochemical proton potential (Ap) to ADP phosphorylation with inorganic phosphate by ATP synthase (Mitchell, 1979). 

The inner membrane of mitochondria is the site of respiratory electron transport and within the inner membrane and the intermembrane space (IMS) of mitochondria are two important copper containing enzymes. First, cytochrome c oxidase (COX) represents the terminal electron acceptor in the respiratory chain and two subunits of this large complex enzyme contain copper sites. A second enzyme in the mitochondria that requires copper is SODl, as described above. Although the vast majority of SODl is cytosolic, a small fraction of this enzyme enters the IMS of the mitochondria where it is believed to directly scavenge superoxide anions produced as a by-product of the electron transport chain. 

The history of the Cyt b c complex itself may be closely related to that of the reaction centers. The occurrence of such a complex in photosynthetic and respiratory electron transport chains of chloroplasts, mitochondria and eubacteria sug-... 

How does the cytochrome subunit of the reaction center regain an electron to complete the cycle The reduced quinone (QH2) is reoxidized to Q by complex III of the respiratory electron-transport chain (Section 18.3.3). The electrons from the reduced quinone are transferred through a soluble cytochrome c intermediate, called cytochrome c 2, in the periplasm to the cytochrome subunit of the reaction center. The flow of electrons is thus cyclic. The proton gradient generated in the course of this cycle drives the generation of ATP through the action of ATP synthase. 

Recent research work has shown that there are in fact two different such reaction centres each receiving energy from two different pigment systems. The situation is further complicated by the fact that flow of electrons from H20 to NADPH2 involves the co-operation of both pigment systems in a sequence of events worked out by Hill and Bendall in 1960 and known as the Z scheme. The Z scheme bears, once again, a remarkable similarity to the respiratory electron transport chain, although it is even more complex and still poorly understood in parts, particularly the identity of many of the electron carriers. It is known, however, that they include plastoquinone, two cytochromes (f and b) and ferredoxin. The photosynthetic phosphorylation of ADP to ATP occurs if the difference in redox potential between the electron carriers is sufficient to allow this endothermic reaction to take... 

A FIGURE 8-15 Heme and iron-sulfur prosthetic groups in the respiratory (electron-transport) chain, (a) Heme portion of cytochromes /jl and fan. which are components of the C0QH2-cytochrome c reductase complex. The same porphyrin ring (yellow) is present in all hemes. The chemical substituents attached to the porphyrin ring differ in the other cytochromes in... 

The rediscovery of cytochromes by Keilin in 1925 led him to propose that the reduction of O2 is linked to the oxidation of reduced substrates by a series of redox reactions, carried out by cellular components collectively referred to as the respiratory electron-transport chain. Progress toward a molecular understanding of these redox reactions has been painfully slow. Most of the components are multisubunit proteins that reside in the inner mitochondrial membrane (Figure 6.11). These proteins (Complexes 1-IV) are quite difficult to purify with retention of in vivo properties, and they do not crystallize well. 

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