Succinate dehydrogenase, mitochondrial

Sodium/glucose cotransporter (rabbit intestinal brush borders)1641 Stearylcoenzyme A desaturase (rat liver microsomal)[651 Subtilopeptidase amylosacchariticus[661 Succinate dehydrogenase (mitochondrial)1671... 

The space inside the inner mitochondrial membrane is called the matrix, and it contains most of the enzymes of the TCA cycle and fatty acid oxidation. (An important exception, succinate dehydrogenase of the TCA cycle, is located in the inner membrane itself.) In addition, mitochondria contain circular DNA molecules, along with ribosomes and the enzymes required to synthesize proteins coded within the mitochondrial genome. Although some of the mitochondrial proteins are made this way, most are encoded by nuclear DNA and synthesized by cytosolic ribosomes. 

Complex II is perhaps better known by its other name—succinate dehydrogenase, the only TCA cycle enzyme that is an integral membrane protein in the inner mitochondrial membrane. This enzyme has a mass of approximately 100 to 140 kD and is composed of four subunits two Fe-S proteins of masses 70 kD and 27 kD, and two other peptides of masses 15 kD and 13 kD. Also known as flavoprotein 2 (FP2), it contains an FAD covalently bound to a histidine residue (see Figure 20.15), and three Fe-S centers a 4Fe-4S cluster, a 3Fe-4S cluster, and a 2Fe-2S cluster. When succinate is converted to fumarate in the TCA cycle, concomitant reduction of bound FAD to FADHg occurs in succinate dehydrogenase. This FADHg transfers its electrons immediately to Fe-S centers, which pass them on to UQ. Electron flow from succinate to UQ,... 

Bonomi, F., Pagani, S., Cerletti, P., and Giori, C., 1983. Modification of die diermodynamic propertie.s of the electron-tran.sferring group.s in mitochondrial. succinate dehydrogenase upon binding of succinate. European Journal of Biochemistry 134 439—445. 

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

Abe K, Saito H. Amyloid beta protein inhibits cellular MTT reduction not by suppression of mitochondrial succinate dehydrogenase but by acceleration of MTT formazan exocytosis in cultured rat cortical astrocytes. Neurosci Res 1998 31 295-305. 

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). 

Bourgeron, T., Rustin, Chretien, D. etal. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency Nat. Genet. 11 44—149, 1995. 

Succinate dehydrogenase is on the inner mitochondrial membrane, where it also functions as complex II of the electron transport chain. 

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. 

Electrons enter the respiratory chain in various different ways. In the oxidation of NADH+H" by complex I, electrons pass via FMN and Fe/S clusters to ubiquinone (Q). Electrons arising during the oxidation of succinate, acyl CoA, and other substrates are passed to ubiquinone by succinate dehydrogenase or other mitochondrial dehydrogenases via en-... 

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). 

The covalent 8a-N(3)-histidyl FAD of mitochondrial succinate dehydrogenase functions as a two-electron acceptor in the oxidation of succinate to fumarate and as a one-electron donor in the reduction of the iron-sulfur centers of the enzyme. Recent ESR spectroscopic data have shown the covalent flavin semiquinone... 

The lysosomal acid phosphatase was cytochemically shown to be present in dense bodies of chondrocytes but not in the nearly matrix vesicles461,462). Subsequent studies have confirmed that the amount of acid phosphatase in isolated vesicles is low and also that the activities of -glucuronidase and cathepsin D in the isolated vesicles were negligible463). The evidence indicates that matrix vesicles are not lysosomal. Isolated vesicles contain comparatively little mitochondrial succinic dehydrogenase, suggesting that the matrix vesicles and mitochondria were not identical458). 

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