Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia/reperfusion mechanisms contribute to lung injury after transplantation, pulmonary embolism, and resolution of atelectasis. Alveolar tissue becomes hypoxic and deprived of substrate only when both ventilation and perfusion are interrupted, a situation modeled in vivo by complete, unilateral lung collapse. Because previously hypoxic mitochondria may be an important intracellular source of superoxide and hydrogen peroxide (H2O2) during reperfusion and re-oxygenation, the authors, in this study, investigated whether mitochondrial H2O2 release changed as a result of lung hypoxia/hypoperfusion resulting from collapse. Mitochondria were isolated from hypoxic (previously collapsed) right or contralateral left rabbits' lungs and from control rabbits' lungs. Mitochondrial H2O2 release, a marker of superoxide production, was measured fluorometrically after incubation with or without 1 mmol/L cyanide and 0.1 mmol/L nicotinamide adenine dinucleotide. Mitochondrial recovery was determined by assaying succinate dehydrogenase activity in mitochondrial preparations and lung homogenates. Lung succinate dehydrogenase activity and mitochondrial recovery were comparable among groups. Calculated lung mitochondrial content did not change (control subjects: left 7.9 +/- 0.5, right 13.8 +/- 1.7; hypoxic: left 10.3 +/- 1.3, right 10.5 +/- 2.4, all mg mitochondrial protein/lung). Mitochondria released hydrogen peroxide at approximately 5.6 nmol/h/mg pro in buffer alone and 14.8 nmol/h/mg pro in buffer with cyanide and nicotinamide adenine dinucleotide. However, lung collapse and resulting hypoxia caused no change in mitochondrial number or capacity to release H2O2 in vitro. Based on these findings, it is suggested that other sources of reactive oxygen metabolites, including xanthine oxidase and activated neutrophils, contribute to the oxidant injury observed in this model.
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PMID:Hydrogen peroxide release by mitochondria from normal and hypoxic lungs. 794 83

Mammalian mitochondria are sensitive targets of the cytotoxic effects of superoxide (O.2-) and nitric oxide (.NO). In turn, when superoxide and nitric oxide are simultaneously produced, they rapidly react with each other yielding the highly oxidizing peroxynitrite anion (ONOO-) which may be also toxic to mammalian mitochondria. In this study we report that peroxynitrite exposure to rat heart mitochondria resulted in significant inactivation of electron carriers such as succinate dehydrogenase and NADH dehydrogenase as well as the mitochondrial ATPase. As a result of enzyme inactivation, peroxynitrite lead to a profound inhibition of glutamate/malate- and succinate-supported oxygen consumption but did not cause mitochondrial uncoupling. Secondary to inhibiting mitochondrial electron transport, peroxynitrite induced an enhanced succinate-stimulated hydrogen peroxide formation by heart mitochondria. Most of the damaging effects against mitochondria can be ascribed to peroxynitrite anion itself and not to hydroxyl radical-like oxidant yielded during the proton-catalyzed decomposition of peroxynitrite, as hydroxyl radical scavengers provided a rather modest protection. Our observations indicate that mitochondria may constitute a key intracellular loci for the toxic effects of peroxynitrite under the various pathological conditions in which peroxynitrite appears to play a contributory role.
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PMID:Inhibition of mitochondrial electron transport by peroxynitrite. 831 80

The structures of the physical complex of d(GCGT).d(ACGC) with the anthracycline antitumor drug nogalamycin were studied in order to determine the sequence specificity and the drug orientation at the symmetric d(C2G3).d(C6G7) binding site of this oligonucleotide. For this purpose, one- and two-dimensional NMR techniques were used in combination with molecular mechanics and molecular dynamics computations. Analysis of the NMR spectra reveals that nogalamycin forms two different intercalation complexes with d(GCGT).d(ACGC). These complexes are called complex I and complex II and are present in a ratio of 0.45:0.55. In both complexes the nogalamycin is intercalated at the d(C2G3).d(C6G7) sequence with the bicyclic and nogalose sugars residing in the major and minor groove, respectively. This results in a buckling of the flanking base pairs and a doubling of the inter-base-pair distances at the intercalation site. In complex I, the aglycon ring of the drug stacks with the C6-G7 bases, and the sugars are directed to the G1.C8 end; while in the case of complex II the anthraquinone ring system is stacked with C2-G3 bases, and the sugars are pointed to the T4.A5 base pair end. The two nogalamycin-d(GCGT).d(ACGC) structures are stabilized by intra- and intermolecular hydrogen bonds, electrostatic interactions, and van der Waals contacts. Comparison of different nogalamycin-oligonucleotide structures reveals a nogalamycin binding specificity to the 3'-side of the cytosine base in cytosine-purine sequences in double-stranded DNA.
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PMID:The antitumor drug nogalamycin forms two different intercalation complexes with d(GCGT).d(ACGC). 843 47

The effect of storage of unfixed cryostat sections from rat liver for 4 h, 24 h, 3 days and 7 days at -25 degrees C was studied on the activities of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, xanthine oxidoreductase, glutamate dehydrogenase, succinate dehydrogenase (all demonstrated with tetrazolium salt procedures), glucose-6-phosphatase (cerium-diaminobenzidine method), 5'-nucleotidase (lead salt method), dipeptidyl peptidase II, acid phosphatase (both simultaneous azo coupling methods), D-amino acid oxidase (cerium-diaminobenzidine-cobalt-hydrogen peroxide procedure) and catalase (diaminobenzidine method). The effect of drying of the cryostat sections at room temperature for 5 and 60 min was investigated as well. The enzyme activities were quantified by cytophotometric measurements of test and control reactions. The test minus control reaction was taken as a measure for specific enzyme activity. It was found that the activities of all the enzymes investigated, with one exception, were affected neither by storage of the cryostat sections at -25 degrees C for up to 7 days, nor by drying of the sections at room temperature for up to 60 min. The exception was xanthine oxidoreductase, whose activity was reduced by 20% after 5 min drying of sections or after 4 h storage. Therefore, only incubations for xanthine oxidoreductase activity have to be performed immediately after cutting cryostat sections, whereas for the other enzymes a considerable margin appears to exist.
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PMID:The effects of storage on the retention of enzyme activity in cryostat sections. A quantitative histochemical study on rat liver. 846 85

Dihydroorotate dehydrogenase (EC 1.3.3.1 or EC 1.3.99.11) catalyzes the fourth sequential step in the de novo synthesis of uridine monophosphate. In eukaryotes it is located in the inner mitochondrial membrane, with ubiquinone as the proximal and cytochrome oxidase as the ultimate electron transfer system, whereas the rest of pyrimidine biosynthesis takes place in the cytosol. Here, the distribution of dihydroorotate dehydrogenase activity in cryostat sections of various rat tissues, and tissue samples of human skin and kidney, was visualized by light microscopy using the nitroblue tetrazolium technique. In addition, a hydrogen peroxide-producing oxidase side-reactivity of dihydroorotate dehydrogenase could be visualized by trapping the peroxide with cerium-diaminobenzidine. The pattern of activity was similar to that of succinate dehydrogenase, but revealed a less intensive staining. High activities of dihydroorotate dehydrogenase were found in tissues with known proliferative, regenerative, absorptive or excretory activities, e.g., mucosal cells of the ileum and colon crypts in the gastrointestinal tract, cultured Ehrlich ascites tumor cells, and proximal tubules of the kidney cortex, whilst lower activities were present in the periportal area of the liver, testis and spermatozoa, prostate and other glands, and skeletal muscle. Dihydroorotate dehydrogenase and succinate dehydrogenase activity in Ehrlich ascites tumor cells grown in suspension culture were quantified by application of nitroblue tetrazolium or cyanotolyl tetrazolium and subsequent extraction of the insoluble formazans with organic solvents. The ratio of dihydroorotate dehydrogenase to succinate dehydrogenase activity was 1:4. This was in accordance with that of 1:5 obtained from oxygen consumption measurement of isolated mitochondria on addition of dihydroorotate or succinate. The ratio determined with mitochondria from animal tissues was up to 1:15 (rat liver, bovine heart). The application of the enzyme inhibitors brequinar sodium and toltrazuril verified the specificity of the histochemical and biochemical methods applied.
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PMID:Catalytic enzyme histochemistry and biochemical analysis of dihydroorotate dehydrogenase/oxidase and succinate dehydrogenase in mammalian tissues, cells and mitochondria. 885 33

In vivo, bicarbonate can affect proximal tubule intermediary metabolism, including gluconeogenesis, ammoniagenesis and maintenance of the mitochondrial substrate supply. In vitro, rabbit proximal tubule cells (RPTC) in primary culture revert from gluconeogenesis to glycolysis and their mitochondrial metabolism remains lower than in vivo. To determine whether the bicarbonate buffer system could have an effect on these deregulations, RPTC in primary culture grown in the absence of insulin and glucose in the culture medium were developed either with the standard sodium bicarbonate buffer with 5% CO2 or with a Hepes hydrogen ion buffer in the presence of 0.5% CO2. Duration of the bicarbonate-free cultures was increased until at least day 17 after seeding, compared with day 11 in bicarbonate-buffered cultures. As could be expected, succinate dehydrogenase activity remained stable as a function of time in bicarbonate-free cultures while an early marked decrease of this activity occurred from seeding in cultures developed in the presence of bicarbonate buffer. Compared to bicarbonate-buffered cells, higher phosphoenolpyruvate carboxykinase activity concomitant with lower intracellular lactate dehydrogenase activity was observed in cultures developed in the absence of bicarbonate, which is indicative of closer carbohydrate metabolism orientation to the in vivo situation for RPTC. Immunofluorescence staining of RPTC with monoclonal antibodies directed to neutral endopeptidase (NEP), and dipeptidyl-peptidase IV (DPP II) showed similar extensive labelling with DPP and NEP in both culture conditions. Confocal microscopy analysis of NEP subcellular distribution, showed exclusive targetting of NEP to the apical plasma membranes. In both models, cAMP production was stimulated by parathyroid hormone and unaffected by arginine vasopressin. In conclusion, bicarbonate withdrawal from the culture medium (without changing the pH of the medium) allows a marked improvement of mitochondrial capacity and carbohydrate metabolism pattern without any loss of differentiated properties.
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PMID:Effects of the medium HCO3-/CO2 buffer system on differentiation and intermediary metabolism properties of rabbit proximal tubule cells in primary culture. 897 88

The growth of the syntrophic propionate-oxidizing bacterium strain MPOB in pure culture by fumarate disproportionation into carbon dioxide and succinate and by fumarate reduction with propionate, formate or hydrogen as electron donor was studied. The highest growth yield, 12.2 g dry cells/mol fumarate, was observed for growth by fumarate disproportionation. In the presence of hydrogen, formate or propionate, the growth yield was more than twice as low: 4.8, 4.6, and 5.2 g dry cells/mol fumarate, respectively. The location of enzymes that are involved in the electron transport chain during fumarate reduction in strain MPOB was analyzed. Fumarate reductase, succinate dehydrogenase, and ATPase were membrane-bound, while formate dehydrogenase and hydrogenase were loosely attached to the periplasmic side of the membrane. The cells contained cytochrome c, cytochrome b, menaquinone-6 and menaquinone-7 as possible electron carriers. Fumarate reduction with hydrogen in membranes of strain MPOB was inhibited by 2-(heptyl)-4-hydroxyquinoline-N-oxide (HOQNO). This inhibition, together with the activity of fumarate reductase with reduced 2,3-dimethyl-1,4-naphtoquinone (DMNH2) and the observation that cytochrome b of strain MPOB was oxidized by fumarate, suggested that menequinone and cytochrome b are involved in the electron transport during fumarate reduction in strain MPOB. The growth yields of fumarate reduction with hydrogen or formate as electron donor were similar to the growth yield of Wolinella succinogenes. Therefore, it can be assumed that strain MPOB gains the same amount of ATP from fumarate reduction as W. succinogenes, i. e. 0.7 mol ATP/mol fumarate. This value supports the hypothesis that syntrophic propionate-oxidizing bacteria have to invest two-thirds of an ATP via reversed electron transport in the succinate oxidation step during the oxidation of propionate. The same electron transport chain that is involved in fumarate reduction may operate in the reversed direction to drive the energetically unfavourable oxidation of succinate during syntrophic propionate oxidation since (1) cytochrome b was reduced by succinate and (2) succinate oxidation was similarly inhibited by HOQNO as fumarate reduction.
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PMID:Investigation of the fumarate metabolism of the syntrophic propionate-oxidizing bacterium strain MPOB. 953 36

Mitochondrial complexes I, II, and III were studied in isolated brain mitochondrial preparations with the goal of determining their relative abilities to reduce O2 to hydrogen peroxide (H2O2) or to reduce the alternative electron acceptors nitroblue tetrazolium (NBT) and diphenyliodonium (DPI). Complex I and II stimulation caused H2O2 formation and reduced NBT and DPI as indicated by dichlorodihydrofluorescein oxidation, nitroformazan precipitation, and DPI-mediated enzyme inactivation. The O2 consumption rate was more rapid under complex II (succinate) stimulation than under complex I (NADH) stimulation. In contrast, H2O2 generation and NBT and DPI reduction kinetics were favored by NADH addition but were virtually unobservable during succinate-linked respiration. NADH oxidation was strongly suppressed by rotenone, but NADH-coupled H2O2 flux was accelerated by rotenone. Alpha-phenyl-N-tert-butyl nitrone (PBN), a compound documented to inhibit oxidative stress in models of stroke, sepsis, and parkinsonism, partially inhibited complex I-stimulated H2O2 flux and NBT reduction and also protected complex I from DPI-mediated inactivation while trapping the phenyl radical product of DPI reduction. The results suggest that complex I may be the principal source of brain mitochondrial H2O2 synthesis, possessing an "electron leak" site upstream from the rotenone binding site (i.e., on the NADH side of the enzyme). The inhibition of H2O2 production by PBN suggests a novel explanation for the broad-spectrum antioxidant and antiinflammatory activity of this nitrone spin trap.
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PMID:Interaction of alpha-phenyl-N-tert-butyl nitrone and alternative electron acceptors with complex I indicates a substrate reduction site upstream from the rotenone binding site. 983 55

Metabolic pathways underlying the regeneration of reduced glutathione were investigated in acutely isolated metabolically active mitochondria from rat forebrain. The application of hydrogen peroxide to the organelles was accompanied by a transient increase in glutathione disulfide. The recovery of reduced glutathione was significantly improved in the presence of alternatively succinate, malate, citrate, isocitrate, or beta-hydroxybutyrate. Inhibition of succinate dehydrogenase by malonate abolished the beneficial effect of succinate on the reduction of glutathione disulfide but did not influence the effect of isocitrate. Fluorocitrate, an inhibitor of aconitase, blocked the effect exerted by citrate but did not inhibit the effects of malate or beta-hydroxybutyrate. Uncoupling of the respiratory chain by carbonyl cyanide m-chlorophenylhydrazone prevented the beneficial effect of beta-hydroxybutyrate but did not abolish the improved reduction of mitochondrial glutathione disulfide in the presence of malate and isocitrate. These results suggest that NADP+-dependent isocitrate dehydrogenase as well as malic enzyme and nicotinamide nucleotide transhydrogenase contribute to the regeneration of NADPH required for the reduction of glutathione disulfide in brain mitochondria.
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PMID:The regeneration of reduced glutathione in rat forebrain mitochondria identifies metabolic pathways providing the NADPH required. 1056 8

A convenient model for studying the mechanisms of biological self-organization is described by morphometric investigation of formation of mitochondrion associations in medium containing physiological concentration of potassium ions without nonpolar substances. Association formation was considerably better at 15-18 degrees C during isolation and storage than at 0 degree C. The existence of filamented mitochondria in homogenate was also shown by staining of succinate dehydrogenase. Formation of associations increased in medium pretreated with negative air ions carrying superoxide and is probably due to hydrogen peroxide. The effect of substances influencing the surface charge on association formation was studied.
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PMID:[Self-organization of mitochondrial associates and effects of negative air ions]. 1073 15


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