Succinate-Q reductase complex

Step f Complex II. When FADH2 is utilized as an electron donor, the succinate-Q reductase complex (Complex II) transfers the electrons from FADH2 to ubiquinone through iron-sulfur centers. This reaction does not have a proton pumping function. 

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. 

Describe the entry of electrons into the respiratory chain at the succinate-Q reductase complex (Complex 11) from flavoproteins such as succinate dehydrogenase (a component of Complex II), glycerol phosphate dehydrogenase, and fatty acyl CoA dehydrogenase by way of FADH.2. Appreciate that Complex II is not a proton pump. 

How can the FADH2 generated by the succinate-Q-reductase complex participate in electron transport if it is not free to diffuse from the enzyme complex Does the oxidation of succinate transport protons ... 

The FADH2 generated by the succinate-Q-reductase complex upon oxidation of succinate transfers it electrons to iron-sulfur center and finally to ubiquinone. No, this system does not transport protons across the inner mitochondrial membrane. 

NADH and FADHg are produced as a result of substrate level dehydrogenations. Oxidation of these reduced coenzymes by oxygen is accomplished by the intervention of a series of electron carriers between the primary reductant and the terminal oxidant (Fig. 2). The electron-transport components represent redox couples of increasing redox potential and are therefore favored thermodynamically. The respiratory chain can be separated into four multienzyme complexes NADH-Q reductase (complex I), succinate-Q reductase (complex II), QH2"Cytochrome c reductase (complex III), and cytochrome c oxidase (complex IV). At each of these successive oxidation-reduction steps, a certain amount of free energy is available, the amount being determined by the difference in the oxidation-reduction potential of the two sequential components. The difference in the redox potential between... 

Succinate-Q reductase (complex II) contains succinate dehydrogenase, FAD, two iron-sulfur centers, and an additional iron-sulfur protein. As with complex I, the substrate binding site of succinate reductase is also on the M side of the membrane (Hatefi and Stiggall, 1976). 

Recall that FADH i is formed in the citric acid cycle, in the oxidation of sue cinate to fumarate by succinate dehydrogenase (p. 487). This enzyme is of the swccineite-Q reductase complex (Complex 11), an integral membrane protein of the inner mitochondrial membrane. FADH does not leave the complex. Rather, its electrons are transferred to Fe-S centers and then toQ for entry into the electron-transport chain. The succinate-Qreductase complex, in contrast with NADFI-Q oxidoreductase, does not transport protons. Consequently, less ATP is formed from the oxidation of FADH than from NADH. 

The components of the respiratory chain contain a variety of redox cofactors. Complex I (NADH-Q reductase > 600 kJDa) contains five iron-sulfur clusters and FMN. Complex II (succinate-Q reductase 150 kDa) contains sev-... 

FIG. 4.2 Malate metabolism in mitochondria from body wall muscle of adult Ascaris smm. (1) Fumarase (2) malic enzyme (3) pyruvate dehydrogenase complex (4) complex I (5) succinate-coenzyme Q reductase (complex II, fumarate reductase) (6) acyl CoA transferase (7) methylmalonyl CoA mutase (8) methyl-malonyl CoA decarboxylase (9) propionyl CoA condensing enzyme (10) 2-methyl acetoacetyl CoA reductase (11) 2-methyl-3-oxo-acyl CoA hydratase (12) electron-transfer flavoprotein (13) 2-methyl branched-chain enoyl CoA reductase (14) acyl CoA transferase. 

Takamiya, S., Furushima, R. and Oya, H. (1986) Electron-transfer complexes of Ascaris suum muscle mitochondria. II. Succinate coenzyme Q reductase (complex II) associated with substrate-reducable cytochrome B g. Biochim. Biophys. Acta 848 99-107. 

Thenoyltrifluoroacetone and carboxin and its derivatives specifically block Complex II, the succinate-UQ reductase. Antimycin, an antibiotic produced by Streptomyees griseus inhibits the UQ-cytochrome c reductase by blocking electron transfer between bn and coenzyme Q in the Q site. Myxothiazol inhibits the same complex by acting at the site. 

NADH coenzyme Q reductase defect (complex I) Succinate coenzyme Q reductase defect (complex II) Coenzyme Q cytochrome C reductase defect (complex III)... 

Fio. 22. Resolution of complex II with respect to succinate dehydrogenase by various chaotropes. Complex II was suspended in 50 mM Tris-HCl, pH 8.0. After addition of 0.6 M chaotrope the concentration of complex II was 8 mg/ml. After addition of the salts, samples were taken at the intervals indicated and assayed for succinate-Qi and succinate-PMS reductase activities. Solid lines, sucdnate-ubiquinone-2(Q) reductase activity dotted line, succinate-PMS reductase activity. Resolution temperature, 0° assay temperature, 38°. The complex II preparations used in the experiments of this and subsequent Figs. 24 and 25 had specific activities between 40 and 45 moles Qj reduced by succinate per min per mg protein. From Davis and Hatefi (169). 

Complex II (succinate dehydrogenase) - Complex II is not in the path traveled by electrons from Complex I (Figure 15.3). Instead, it is a point of entry of electrons from FADH2 produced by the enzyme succinate dehydrogenase in the citric acid cycle. Both complexes I and II donate their electrons to the same acceptor, coenzyme Q. Complex II, like complex I, contains iron-sulfur proteins, which participate in electron transfer. It is also called succinate-coenzyme Q reductase because its electrons reduce coenzyme Q. 

Succinate dehydrogenase (also called succinate-coenzyme Q reductase or Complex II) is an enzyme of the citric acid cycle and glyoxylate cycle that catalyzes the reaction below ... 

Complex II, also known as succinate-coenzyme Q reductase, accepts electrons from succinate formed during the TCA cycle (see the previous chapter). Electrons flow from succinate to FAD (the flavin-adenine dinucleotide) coenzyme, through an iron-sulfur protein and a cytochrome bsso protein (the number refers to the wavelength where the protein absorbs), and to coenzyme Q. No protons are translocated by Complex II. Because translocated protons are the source of the energy for ATP synthesis, this means that the oxidation of a molecule of FADH2 inherently leads to less ATP synthesized than does the... 

A protein complex capable of rapidly reducing coenzyme Q in the presence of succinate (succinic coenzyme Q reductase), NADH (NADH coenzyme Q reductase), and cytochrome c (cytochrome c coen-... 

Such a process is supposed to occur within the limits of Q-cycle mechanism (Figure 23.2). In accord with this scheme ubihydroquinone reduced dioxygen in Complex III, while superoxide producers in Complex I could be FMN or the FeS center [12]. Zhang et al. [24] also suggested that the Q-cycle mechanism is responsible for the superoxide production by the succinate-cytochrome c reductase in bovine heart mitochondria and that FAD of succinate dehydrogenase is another producer of superoxide. Young et al. [25] concluded that, in addition to Complex III, flavin-containing enzymes and FeS centers are also the sites of superoxide production in liver mitochondria. 

Abnormalities of the respiratoiy chain. These are increasingly identified as the hallmark of mitochondrial diseases or mitochondrial encephalomyopathies [13]. They can be identified on the basis of polarographic studies showing differential impairment in the ability of isolated intact mitochondria to use different substrates. For example, defective respiration with NAD-dependent substrates, such as pyruvate and malate, but normal respiration with FAD-dependent substrates, such as succinate, suggests an isolated defect of complex I (Fig. 42-3). However, defective respiration with both types of substrates in the presence of normal cytochrome c oxidase activity, also termed complex IV, localizes the lesions to complex III (Fig. 42-3). Because frozen muscle is much more commonly available than fresh tissue, electron transport is usually measured through discrete portions of the respiratory chain. Thus, isolated defects of NADH-cytochrome c reductase, or NADH-coenzyme Q (CoQ) reductase suggest a problem within complex I, while a simultaneous defect of NADH and succinate-cytochrome c reductase activities points to a biochemical error in complex III (Fig. 42-3). Isolated defects of complex III can be confirmed by measuring reduced CoQ-cytochrome c reductase activity. 

Electrons enter the ETC at respiratory Complexes I and II. The electrons from NADH enter at respiratory Complex I (RC I, NADH dehydrogenase) with the concomitant oxidation of NADH to NAD+. The electrons carried by FADH2 are transferred to RC II (succinate dehydrogenase) as the FADH2 is oxidized to FAD and succinate is reduced to fumarate. These electrons from RC I and II are transferred to the quinone form of coenzyme Q (CoQ), which delivers them to RC III (UQ-cytochrome c reductase). Cytochrome c then accepts the electrons from RC III, and the reduced cytochrome c is reoxidized as it delivers the electrons to RC IV, cytochrome c oxidase. The electrons are then used by RC IV to reduce molecular oxygen to water. 

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