Succinate: ubiquinone oxidoreductase Complex

Figure 12-7. Proposed sites of inhibition (0) of the respiratory chain by specific drugs, chemicals, and antibiotics. The sites that appear to support phosphorylation are indicated. BAL, dimercaprol. TTFA, an Fe-chelating agent. Complex I, NADHiubiquinone oxidoreductase complex II, succinate ubiquinone oxidoreductase complex III, ubiquinohferricytochrome c oxidoreductase complex IV, ferrocytochrome ctoxygen oxidoreductase. Other abbreviations as in Figure 12-4.

Hydrogenase (D. desulfuricans) Succinate-ubiquinone oxidoreductase (complex II) Aconitase (inactive) 83 000 0... 

Figure 7-1. Pathways of fuel metabolism and oxidative phosphorylation. Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis, or for oxidation to acetyl-CoA by the pyruvate dehydrogenase complex (PDC). Long-chain fatty acids are transported into mitochondria, where they undergo [ -oxidation to ketone bodies (liver) or to acetyl-CoA (liver and other tissues). Reducing equivalents (NADH, FADII2) are generated by reactions catalyzed by the PDC and the tricarboxylic acid (TCA) cycle and donate electrons (e ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (Complex 0 or at succinate ubiquinone oxidoreductase (Complex ID- Cytochrome c oxidase (Complex IV) catalyzes the reduction of molecular oxygen to water, and ATP synthase (Complex V) generates ATP fromADP Reprinted with permission from Stacpoole et al. (1997).

In metazoans, the electron transport chain consists of four integral membrane complexes localized to the inner mitochondrial membrane complex I (NADH-ubiquinone oxidoreductase), complex II (succinate-ubiquinone oxidoreductase), complex III (ubiquinol-cytochrome c oxidoreductase) and complex IV (cytochrome c oxidase), plus coenzyme Q (ubiquinone) and cytochrome c. As first shown by Fry and Beesley (1991), the plasmodial electron transport chain differs from the metazoan system in lacking complex I however, a single subunit NADH dehydrogenase is present and is homologous to that found in plants, bacteria and yeast but not in animals (Krungkrai, 2004 Vaidya, 2004,2005 van Dooren et al., 2006). 

Figure 8.11. Stereo view of Wolinella succinogenes fumarate reductase dimer, an analogue of mitochondrial succinate ubiquinone oxidoreductase (Complex II) of the electron transport chain. (A) Ligands in ball and stick representation and waters of Thales shown as light dots. (B) Ligands in space-...

Complex II (Succinate Dehydrogenase Succinate Ubiquinone Oxidoreductase)... 

Saruta, F., Kuramochi, T., Nakamura, K, Takamiya, S., Yu, Y., Aoki, T., Sekimizu, K., Kojima, S. and Kita, K. (1995) Stage-specific isoforms of complex II (succinate-ubiquinone oxidoreductase) in mitochondria from the parasitic nematode, Ascaris suum. Journal of Biological Chemistry 270, 928-932. 

In the mitochondria, ONOO- can mediate damage to OXPHOS by nitrosylat-ing/oxidizing tyrosine or thiol functional groups, rendering catalytic inactivation of complex I [NADH ubiquinone oxidoreductase], complex II [succinate ubiquinone oxidoreductase] and complex V (FI, FO-ATPase), thereby impeding ETC/ OXPHOS... 

These complexes are usually named as follows I, NADH-ubiquinone oxidoreductase II, succinate-ubiquinone oxidoreductase III, ubiquinol-cytochrome c oxidoreductase IV, cytochrome c oxidase. The designation complex V is sometimes applied to ATP synthase (Fig. 18-14). Chemical analysis of the electron transport complexes verified the probable location of some components in the intact chain. For example, a high iron content was found in both complexes I and II and copper in complex IV. 

The mitochondrial respiratory chain, which contains at least 13 Fe-S clusters (Figure 6), perhaps best illustrates the importance of Fe-S clusters in membrane-bound electron transport. Electrons enter via three principal pathways, from the oxidation of NADH to NAD+ (NADH-ubiquinone oxidoreductase or Complex I) and succinate to fumarate (succinate ubiquinone oxidoreductase or Complex II), and from the /3-oxidation of fatty acids via the electron transferring flavoprotein (ETF-ubiquinone oxidoreductase). All three pathways involve a complex Fe S flavoprotein dehydrogenase, that is, NADH dehydrogenase, succinate dehydrogenase, and ETF dehydrogenase, and in each case the Fe-S clusters mediate electron transfer from the flavin active site to the ubiquinone pool via protein-associated ubiquinone. 

Complex II is usually measured in two ways either as succinate ubiquinone oxidoreductase or as succinate cytochrome c oxidoreductase. The most commonly used assay for succinate ubiquinone oxidoreductase (or isolated complex II) uses DCIP in the same way as described above for the new complex I assay, only in this case succinate is added as a substrate (instead of NADH). The specificity of DCIP reduction can be determined by measuring in the presence or absence of mal-onate, a specific inhibitor of complex II. The assay for succinate cytochrome c oxidoreductase (or complex II 4- HI) uses succinate and oxidized cytochrome c as substrates and measures the reduction of cytochrome c, which can be followed spectrophotometrically at 550 nm. The assay is also suitable to screen for coenzyme Q deficiencies, as it is dependent on the endogenously present CoQio- In case of a CoQ deficiency, a reduced succinate cytochrome c oxidoreductase activity will be... 

The mitochondrial respiratory chain is composed of more than 80 proteins grouped into 5 distinct complexes that form an integrated electron transfer chain (ETC, Figure 4). Initiation of electron transport takes place either from complex I (reduced nicotinamide adenine diphosphate (NADH)—ubiquinone oxidor-eductase) or from complex II (succinate—ubiquinone oxidoreductase) to complex III (ubiquinol—cytochrome c oxidoreductase) by ubiquinone (UQ, coenzyme Q, 39). As shown in Scheme 1, ubiquinone is reduced to... 

When mitochondria from bovine heart were solubilized by treatment with mild detergents it was possible to separate and purify the sections of the respiratory chain referred to earlier as coupling sites 1, 2 and 3. These were named Complex I (NADH-ubiquinone oxidoreductase), Complex III (ubiquinol-cytochrome c ox-idoreductase, cytochrome bci complex) and Complex IV (cytochrome c oxidase) [17], and have since been characterized as independent entities, although it is now recognized that these three complexes co-assemble with specific stoichiometry to form respiratory chain supercomplexes or respirasomes in fungal, plant and mammalian mitochondria [18-20]. There is also evidence that succinate-ubiquinone oxidoreductase (which was purified alongside the other complexes and named Complex II [21]) forms a tight association with Complex III in yeast mitochondria [22]. 

Figure 8.8. Stereo view of E. coli succinate ubiquinone oxidoreductase, which is an analogue of Complex II of the electron transport chain of mitochondria, with neutral residues light gray, aromatics black, other hydrophobics gray, and charged residues white. (A) Space-filling representation with water...

Figure 1 shows the complex ESR spectra from isolated cardiac mitochondria. They appear as a superposition of spectra from various paramagnetic components of the mitochondrial ETC. They are mainly iron-sulfur centers, denoted as Nl, N2, N3 - - 4 (located in complex I, NADFi-ubiquinone oxidoreductase), SI (complex II, succinate-ubiquinone oxidoreductase), and the Rieske iron-sulfur protein (complex III, ubihydroquinone-cytochrome C oxidoreductase). The positions of the components... 

Because of the known action of taxol, Manzano et al. [137] initiated state 3 respiration in isolated mitochondria by the addition of 0.8 mM ADP together with one specific substrate of each respiratory chain complex. These were 10 mM pyruvate (NADH-ubiquinone oxidoreductase, complex I), 1 mM succinate (succinate dehydrogenase, complex II) or 0.2 mM ascorbate and 10 pM tetramethyl-/7-phenylenediamine (cytochrome oxidase). The addition of taxol strongly reduced the respiratory capacity of complex I and complex II by 58% and 45%, respectively, without affecting cytochrome oxidase. Thus, they found a direct effect on respiratory metabolism. This is presumably because the change to mitochondrial bcl protein in the intermembrane space caused the release of cytochrome c [138] and can lead to the apoptotic cascade (see Section 5,2.2). 

The electron carriers in the respiratory assembly of the inner mitochondrial membrane are quinones, flavins, iron-sulfur complexes, heme groups of cytochromes, and copper ions. Electrons from NADH are transferred to the FMN prosthetic group of NADH-Q oxidoreductase (Complex I), the first of four complexes. This oxidoreductase also contains Fe-S centers. The electrons emerge in QH2, the reduced form of ubiquinone (Q). The citric acid cycle enzyme succinate dehydrogenase is a component of the succinate-Q reductase complex (Complex II), which donates electrons from FADH2 to Q to form QH2.This highly mobile hydrophobic carrier transfers its electrons to Q-cytochrome c oxidoreductase (Complex III), a complex that contains cytochromes h and c j and an Fe-S center. This complex reduces cytochrome c, a water-soluble peripheral membrane protein. Cytochrome c, like Q, is a mobile carrier of electrons, which it then transfers to cytochrome c oxidase (Complex IV). This complex contains cytochromes a and a 3 and three copper ions. A heme iron ion and a copper ion in this oxidase transfer electrons to O2, the ultimate acceptor, to form H2O. 

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