Succinic dehydrogenase-cytochrome

FIGURE 1. Respiratory chain the enzymes of the mitochondrial iimer membrane involved in oxidative phosphorylation. From complex I to V, they are NADH-dehydrogenase, succinate dehydrogenase, cytochrome bc complex, and cytochrome c oxidase. Protons are translocated across the membrane while electrons are transferred to Oj through the chain. The proton gradient is used by ATP synthase (complex V) to make ATP. (Reprinted with permission from Saraste, 1999, American Association for the Advancement of Science.)... 

Succinic dehydrogenase Cytochrome oxidase Acid phosphatase Aryl sulfatase Catalase... 

Succinate dehydrogenase Cytochrome c oxidase Citrate synthase Carbon—nitrogen lyases Forming carbon—nitrogen bonds Acting on carbon-nitrogen bonds, other than peptide bonds Chitinase... 

In contrast with the fall in the activity of muscle glycolytic enzymes in human muscular dystrophy, Dreyfus and his colleagues (DIO) found little or no decrease in the concentrations of certain enzymes involved in oxidative breakdown of fuel, notably succinate dehydrogenase, cytochrome oxidase, fumarase, and aconitase. In the mouse myopathy, the concentration of cytochrome oxidase is increased (W12) elevated levels of respiratory enzymes have been reported also in myopathy resulting from vitamin E deficiency (D6) and in genetically dystrophic chickens... 

Iron Succinate dehydrogenase Cytochromes a, b and c Aerobic oxidation of carbohydrates Electron transfer... 

Cytochromes in Mitochondria. The majority of cytochromes occur entirely in mitochondria, where they are associated with large amounts of lipid. An intimate association exists between the cytochromes and succinic dehydrogenase to form succinoxidase, which retains the ability to oxidize succinate after all other oxidative reactions have been washed out of the particles. The activity of the succinoxidase system is sensitive to many environmental factors, which apparently influence the physical state of the particles. When mitochondria are exposed to distilled water, for example, cytochrome c is lost. Exogenous cytochrome c is used much less efficiently than particle-bound cytochrome. It is concluded from observations of this sort that the individual components, succinic dehydrogenase, cytochrome c, cytochrome a, and cytochrome oxidase, together with any other factors that may be involved, are fixed in position to react rapidly with each other, and do not depend on diffusion. 

Charbonnier, J., H. D. Moussard, P. Iselin, and J. L. Soule, 1959. Action of silica in solution on the succinic dehydrogenase cytochrome oxidase enzyme system. Compt. Rend. Soc. Biol. 153 1492. 

Barbiturates such as amobarbital inhibit NAD-hnked dehydrogenases by blocking the transfer from FeS to Q. At sufficient dosage, they are fatal in vivo. Antin cin A and dimercaprol inhibit the respiratory chain between cytochrome b and cytochrome c. The classic poisons H2S, carbon monoxide, and cyanide inhibit cytochrome oxidase and can therefore totally arrest respiration. Malonate is a competitive inhibitor of succinate dehydrogenase. 

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. 

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). 

Complex II (which is not shown in the figure) contains succinate dehydrogenase, the FAD-dependent Krebs cycle enzyme and, like Complex I, transfers its electrons through iron-sulfur centres and a 6-type cytochrome (more of these haem iron proteins will be discussed in Chapter 13) to CoQ. However, here AEI is only 0.085 V, corresponding to AG° of —16.4 kJ/mol, which is not sufficient to allow proton pumping. 

In addition to binding to cytochrome c oxidase, cyanide inhibits catalase, peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, and succinic dehydrogenase activities. These reactions may make contributions to the signs of cyanide toxicity (Ardelt et al. 1989 Rieders 1971). Signs of cyanide intoxication include an initial hyperpnea followed by dyspnea and then convulsions (Rieders 1971 Way 1984). These effects are due to initial stimulation of carotid and aortic bodies and effects on the central nervous system. Death is caused by respiratory collapse resulting from central nervous system toxicity. 

As described elsewhere in this chapter, alterations in the activity of a number of lung enzymes have been described after acute and chronic ozone exposure. With the possible exceptions of the sulfhydryl-containing enzyme succinic dehydrogenase and the cytochrome P-4 en me benzopyrene hydroxylase, it is difficult to determine whether these findings are due to a direct oxidative effect of ozone or are secondary to changes in protein synthesis, concentrations of intermediates, or destruction of cells or organelles. 

Freebaim noted a decrease in oxygen uptake of plant and bovine liver mitochondria that was reversible by glutathione and ascorbic acid. The activity of some mitochondrial enzymes, including succinic dehydrogenase and cytochrome oxidase, has been found to be susceptible to ozone. 

Oxidizible substrates from glycolysis, fatty acid or protein catabolism enter the mitochondrion in the form of acetyl-CoA, or as other intermediaries of the Krebs cycle, which resides within the mitochondrial matrix. Reducing equivalents in the form of NADH and FADH pass electrons to complex I (NADH-ubiquinone oxidore-ductase) or complex II (succinate dehydrogenase) of the electron transport chain, respectively. Electrons pass from complex I and II to complex III (ubiquinol-cyto-chrome c oxidoreductase) and then to complex IV (cytochrome c oxidase) which accumulates four electrons and then tetravalently reduces O2 to water. Protons are pumped into the inner membrane space at complexes I, II and IV and then diffuse down their concentration gradient through complex V (FoFi-ATPase), where their potential energy is captured in the form of ATP. In this way, ATP formation is coupled to electron transport and the formation of water, a process termed oxidative phosphorylation (OXPHOS). 

Increase in activity of cerebral succinic dehydrogenase and brain acid proteinase, and in brain RNA concentration decrease in liver cytochrome P-450 activity (22)... 

Correct answer = D. Thirteen of the approximately 100 polypeptides required for oxidative phosphorylation are coded for by mitochondrial DNA, including the electron transport components cytochrome c and coenzyme Q. Oxygen directly oxidizes cytochrome oxidase. Succinate dehydrogenase directly reduces FAD. Cyanide inhibits electron flow, proton pumping, and ATP synthesis. 

Cytochromes b of mitochondrial membranes are involved in passing electrons from succinate to ubiquinone in complex II138 and also from reduced ubiquinone to cytochrome c, in the 248-kDa complex III (Fig. 18-8). A similar complex is present in photosynthetic purple bacteria.123 139 Cytochrome b560 functions in the transport of electrons from succinate dehydrogenase to ubiquinone,138 and cytochrome b561 of secretory vesicle membranes has a specific role in reducing ascorbic acid radicals.140... 

Enzymes. Heme serves as the prosthetic group lor catalase, peroxidase, cytochrome oxidase, and the related cytochromes. Catalase and peroxidase iron are presumably present in the ferric form while the iron of Ihe cytochromes may exist in Ihe reduced or oxidized lorni. A number of tlasoproteins. including succinic dehydrogenase, contain iron in ihe molecule. Iron appears to act as coeiuyme for aeonilase. A number of other enzymes require the presence of iron for their activities,... 

Oxidation of a-amino acids to keto acids catalysed by D- and L-amino acid oxidases Oxidation of NADH via the cytochrome system catalyzed by cytochrome reductase Energy production via the TCA or Krebs cycle catalyzed by succinate dehydrogenase Fatty acid oxidation catalyzed by acyl-coenzyme A dehydrogenases Synthesis of fatty acids from acetate (80,81)... 

The multisubunit complexes of the respiratory chain. Complexes I (NADH dehydrogenase) and II (succinate dehydrogenase) transfer electrons from NADH and succinate to UQ. Complex III (the cytochrome bc complex) transfers electrons from UQH2 to cytochrome c, and complex IV (cytochrome oxidase), from cytochrome c to 02. The arrows represent paths of electron flow. NADH and succinate provide electrons from the matrix side of the inner membrane, and 02 removes electrons on this side. Cytochrome c is reduced and oxidized on the opposite side of the membrane, in the lumen of a crista or in the intermembrane space. 

Approximately 2.5 molecules of ADP can be phosphorylated to ATP for each pair of electrons that traverse the electron-transport chain from NADH to 02. About 1.5 molecules of ATP are formed for a pair of electrons that enter the chain via succinate dehydrogenase or other flavoproteins such as glycerol-3-phosphate dehydrogenase. Approximately one molecule of ATP is formed for each pair of electrons that enters via cytochrome c. Electron flow through each of complexes I, III, and IV thus is coupled to phosphorylation. 

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