Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxidative enzyme system of the synovial membrane and rheumatoid node from rheumatoid arthritic patients has been studied by histochemical and biochemical methods. As compared to the control synovial membranes, succinic dehydrogenase activity was substantially higher in the rheumatoid arthritic synovial membranes, and was still higher in the rheumatoid nodes, in which only the cells forming the palisade had succinic dehydrogenase activity. As compared to the controls, in response to menadione succinic dehydrogenase was significantly activated. The reducible ubiquinone content of the rheumatoid synovial membrane and the rheumatoid node was by several orders of magnitude higher than in the controls.
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PMID:Electron transporting enzymes of rheumatoid connective tissue. 61 16

Tetrahymena pyriformis ST (3 X 10-4 cells/ml) was treated with 0.1 mg/ml chloramphenicol (CAP). Cell division ceased after 1.5 divisions with no decreased viability. Total mitochondrial volume and succinic dehydrogenase (SDH) activity/liter increased 1.7-fold and 3-fold, respectively. SDH activity/cell decreased whereas malate dehydrogenase activity/cell and respiratory control ratios and P:O ratios of isolated mitochondria were unchanged in treated cells. During 12 hours of growth in CAP the total surface area of mitochondrial inner and outer membrane was essentially unchanged or increased 4-fold, respectively. Mitochondria from cells treated with chloramphenicol had decreased size, buoyant density and protein:lipid ratio in the membranes. The membrane ubiquinone:protein ratio was unchanged. Tetrahymena cells contained 3.6 X 10-minus 12 g of mitochondrial DNA and 6,800 mitochondria in a volume of 41,000 mu-3. A 4-hour treatment with CAP caused a 4-fold increase in the number of mitochondria/cell and a 10-fold increase in mitochondria/liter in contrast to a 4-fold increase in number of mitochondria/liter in control cells. Thus CAP stimulated division of mitochondria. Individual mitochondria of treated cells had one-tenth the volume of control mitochondria. The rate of increase of mitochondrial DNA/liter was the same in control and CAP-treated cultures. The amount of DNA/mitochondrion decreased 75% in CAP-treated cells due to the rapid division of mitochondria. The cell volume, cell protein content and mitochondrial DNA content/cell decreased with growth of control cultures.
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PMID:Effect of chloramphenicol on replication of mitochondria in Tetrahymena. 80 71

Within 3 days after dextralateral nephrectomy the weight of left kidney was increased by 24.0%, yield of mitochondrial protein--on the average, by 38.0%, the succinate dehydrogenase activity--by 40.0%. Content of ubiquinone was essentially unaltered in kidney within 3 days after the nephrectomy; in mitochondria concentration of the coenzyme (calculated per mg of protein) was decreased at the 3-rd day after the operation. Biosynthesis of ubiquinone was increased at the 2-nd day after the nephrectomy in slices of hypertrophied kidney; it was studied by incorporation of 1-14C-acetate. Biosynthesis of cholesterol was increased at the same time, especially within the 1-st and 2-nd days after the operation. Content of cholesterol was increased in hypertrophied kidney within the 3-rd day after the operation.
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PMID:[Ubiquinone and cholesterol content and biosynthesis in the hypertrophied kidney of white rats following unilateral nephrectomy]. 102 31

When incubated in an air atmosphere, solubilized succinate dehydrogenase (succinate:(acceptor) oxidoreductase, EC 1.3.99.1) quickly loses the capability to recombine with membrane components to catalyze mitochondrial related electron transport activities. At 0 degrees the loss in reconstitution capability is a first-order process; the half-life of the enzyme is 1.6 hr at this temperature. The enzyme is stabilized by recombining it with submitochondrial particles or with a cytochrome b preparation-phospholipid mixture. The presence of the cytochrome b preparation in the succinate dehydrogenase-cytochrome b-phospholipid complex is obligatory, indicating that protein-protein interactions between succinate dehydrogenase and other membrane components are important in stabilizing the capability of the flavoprotein to transfer electrons to other respiratory components. Treatment of this complex with phospholipase C results in loss of most of the succinate-dichlorophenolindophenol reductase activity and almost complete hydrolysis of phospholipid. Succinate dehydrogenase maintains its capability to participate in mitochondrial electron transport for several hours if the phospholipase treated complex is reconstituted with lysolecithin at the time of assay. Phospholipids are therefore not required for the stabilization process, but rather for formation of an active reductase complex. A lipophilic environment, if required for stabilization, can be provided by diglycerides. Diglycerides also can provide an environment conducive to electron transfer from succinate to ubiquinone but do so less efficiently than intact phospholipids.
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PMID:The role of protein and lipids in stabilizing the activity of bovine heart succinate dehydrogenase. 112 75

Structural mitochondrial damage accompanies the cytotoxic effects of several drugs including tumor necrosis factor (TNF). Using various inhibitors of mitochondrial electron transport we have investigated the mechanism of TNF-mediated cytotoxicity in L929 and WEHI 164 clone 13 mouse fibrosarcoma cells. Inhibitors with different sites of action modulated TNF cytotoxicity, however, with contrasting effects on final cell viability. Inhibition of mitochondrial electron transport at complex III (cytochrome c reductase) by antimycin A resulted in a marked potentiation of TNF-mediated injury. In contrast, when the electron flow to ubiquinone was blocked, either at complex I (NADH-ubiquinone oxidoreductase) with amytal or at complex II (succinate-ubiquinone reductase) with thenoyltrifluoroacetone, cells were markedly protected against TNF cytotoxicity. Neither uncouplers nor inhibitors of oxidative phosphorylation nor complex IV (cytochrome c oxidase) inhibitors significantly interfered with TNF-mediated effects, ruling out the involvement of energy-coupled phenomena. In addition, the toxic effects of TNF were counteracted by the addition of antioxidants and iron chelators. Furthermore, we analyzed the direct effect of TNF on mitochondrial morphology and functions. Treatment of L929 cells with TNF led to an early degeneration of the mitochondrial ultrastructure without any pronounced damage of other cellular organelles. Analysis of the mitochondrial electron flow revealed that TNF treatment led to a rapid inhibition of the mitochondria to oxidize succinate and NADH-linked substrates. The inhibition of electron transport was dose-dependent and became readily detectable 60 min after the start of TNF treatment, thus preceding the onset of cell death by at least 3-6 h. In contrast, only minor effects were observed on complex IV activity. The different effects observed with the mitochondrial respiratory chain inhibitors provide suggestive evidence that mitochondrial production of oxygen radicals mainly generated at the ubisemiquinone site is a causal mechanism of TNF cytotoxicity. This conclusion is further supported by the protective effect of antioxidants as well as the selective pattern of damage of mitochondrial chain components and characteristic alterations of the mitochondrial ultrastructure.
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PMID:Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. 131 87

1,2,3,4-Tetrahydroisoquinoline (TIQ), which is structurally similar to MPTP, has been found in human brain and has been reported to inhibit the mitochondrial respiration as does 1-methyl-4-phenylpyridinium ion (MPP+). However, the potency of inhibition by TIQ is less than that of MPP+. In this study, we report the effects of N-methyl-1,2,3,4-tetrahydroisoquinoline (N-Me-TIQ) and N-methylisoquinolinium ion (N-Me-IQ+) on the mitochondrial electron transport system using mitochondria prepared from mouse brains. Five mM N-Me-TIQ and 500 microM N-Me-IQ+ inhibited complex I activity to 54% and 63% of the control, respectively. The IC50 of N-Me-TIQ and N-Me-IQ+ were approximately 6.5 mM and 650 microM, respectively. Neither substance inhibited complex II, III and IV activities. Kinetic analyses of N-Me-IQ+ on complex I activity revealed uncompetitive inhibition against NADH and non-competitive inhibition against ubiquinone. These inhibitory characteristics were the same to those of MPP+ and the inhibitory potency of N-Me-IQ+ on complex I activity was stronger than that of MPP+.
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PMID:Selective inhibition of complex I by N-methylisoquinolinium ion and N-methyl-1,2,3,4-tetrahydroisoquinoline in isolated mitochondria prepared from mouse brain. 135 9

Nitric oxide (NO) is an important signal substance in cell-cell communication and can induce relaxation of blood vessels by activating guanylate cyclase in smooth muscle cells (SMCs). NO is synthesized from L-arginine by the enzyme NO synthase, which is present in endothelial cells. It was recently shown that SMCs may themselves produce NO or an NO-related compound. We have studied NO production and its effects on energy metabolism in cultured rat aortic smooth muscle cells. It was observed that the cytokines, interferon-gamma and tumor necrosis factor-alpha, synergistically induced an arginine-dependent production of NO in these cells. This was associated with an inhibition of complex I (NADH: ubiquinone oxidoreductase) and complex II (succinate: ubiquinone oxidoreductase) activities of the mitochondrial respiratory chain, suggesting that NO blocks mitochondrial respiration in these cells. Lactate accumulated in the media of the cells, implying an increased anaerobic glycolysis, but there was no reduction of viability. An NO-dependent inhibition of mitochondrial respiration and a switch to anaerobic glycolysis would reduce energy production of the SMCs. This would in turn reduce the contractile capacity of the cell and might represent another NO-dependent vasodilatory mechanism. It could be of particular importance in inflammation, since cytokines released by inflammatory cells may induce autocrine NO production in SMCs.
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PMID:Interferon-gamma and tumor necrosis factor synergize to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth muscle cells. 139 84

The sequence of an allele encoding the iron-sulphur protein (Ip) subunit of succinate dehydrogenase (Sdh) was determined following PCR amplification of genomic DNA from a carboxin (Cbx)-sensitive Ustilago maydis strain. Comparison of this sequence with that of the Ip allele from a Cbx-resistant strain (IPr) revealed a two-base difference between the sequences. This mutation led to the substitution of a leucine residue for a histidine residue within the third cysteine-rich cluster of the deduced amino-acid sequence of the Ipr allele. This cluster, which is associated with the S3 iron-redox centre, is involved in the transport of electrons from succinate to ubiquinone (Q). Confirmation that this nucleotide change led to enhanced resistance to Cbx was obtained following mutagenesis of the sensitive Ip allele to the resistant form and expression of the mutated allele in U. maydis.
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PMID:A single amino-acid change in the iron-sulphur protein subunit of succinate dehydrogenase confers resistance to carboxin in Ustilago maydis. 142 16

In mitochondria, electrons derived from the oxidation of succinate by the tricarboxylic acid cycle enzyme succinate-ubiquinone oxido-reductase are transferred directly to the quinone pool. Here we provide evidence that the soluble form of this enzyme (succinate dehydrogenase) behaves as a diode that essentially allows electron flow in one direction only. The gating effect is observed when electrons are exchanged rapidly and directly between fully active succinate dehydrogenase and a graphite electrode. Turnover is therefore measured under conditions of continuously variable electrochemical potential. The otherwise rapid and efficient reduction of fumarate (the reverse reaction) is severely retarded as the driving force (overpotential) is increased. Such behaviour can arise if a rate-limiting chemical step like substrate binding or product release depends on the oxidation state of a redox group on the enzyme. The observation provides, for a biological electron-transport system, a simple demonstration of directionality that is enforced by kinetics as opposed to that which is assumed from thermodynamics.
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PMID:Diode-like behaviour of a mitochondrial electron-transport enzyme. 154 73

When succinate and ADP-Fe3+ chelate were added to beef heart submitochondrial particles pretreated with 2-thenoyltrifluoroacetone, an inhibitor of succinate dehydrogenase of the mitochondrial respiratory chain, the formation of malondialdehyde was observed. No formation was observed without the pretreatment. Oxaloacetate competitively inhibited the malondialdehyde formation with an apparent Ki of 3.4 microM. The malondialdehyde formation seemed to be initiated at the location between the p-hydroxymercuribenzoate-sensitive site and the 2-thenoyltrifluoroacetone-sensitive site of the succinate dehydrogenase because it was inhibited by the mercurial. Ubiquinone-10 was rapidly destroyed during the malondialdehyde-forming reaction when it was in the oxidized form, while the ubiquinone was not destroyed and the malondialdehyde formation was abolished when about 50% of the ubiquinone in the particles was in the reduced state. These observations suggest that the succinate-dependent peroxidation is strongly controlled by the redox state of ubiquinone.
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PMID:Succinate-dependent lipid peroxidation and its prevention by reduced ubiquinone in beef heart submitochondrial particles. 157 4


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