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)

A previous study of endotoxemia in dogs demonstrated that exogenous prostacyclin (PGI2), normally a product of vascular endothelium, restored the cardiac index to normal and improved survival. To account for these results, a study was undertaken to test whether PGI2 would alter isolated rat or dog cardiac mitochondrial function following incubation with plasma from endotoxemic animals. A group of five animals served as anesthetized controls. A second group of seven mongrel dogs was given 1.75 mg Escherichia coli endotoxin/kg and was observed for 5 hours without treatment. Anesthesia did not alter cardiopulmonary function; however, 30 minutes after endotoxin administration, the cardiac index decreased from 148 +/- 25 (mean +/- SD) to 111 +/- 12 ml/kg . min (P less than 0.05) and further decreased to 89 +/- 20 ml/kg . min after 4 hours. Dog plasma obtained 2 to 5 hours after endotoxin infusion, incubated with rat or dog myocardial mitochondria, decreased succinate dehydrogenase (SDH) activity (P less than 0.05) and depressed mitochondrial respiration in the presence of the substrate succinate and adenosine diphosphate (ADP) from 180 to 87 Natoms oxygen/mg protein . min (P less than 0.05). There was no change in oxygen consumption when substrate alone was present, nor did plasma alter the amount of ADP phosphorylation as a function of oxygen consumption. A third group of seven animals, 30 minutes after administration of 1.75 mg endotoxin/kg, was treated with 100 ng/kg . min PGI2 for 3 hours. PGI2 infusion in this group prevented the decrease in cardiac index. Plasma obtained during and after PGI2 infusion did not decrease mitochondrial SDH activity, which remained higher than that in controls (P less than 0.001); mitochondrial respiration was also not altered. A correlation was observed between cardiac index and SDH activity (r = 0.58, P less than 0.001) and between cardiac index and mitochondrial respiration (r = 0.61, P less than 0.001). In PGI2-treated dogs cardiac mitochondria were functionally and structurally normal in contrast to the depression and disruption produced by endotoxemia, as observed by enzymatic assay as well as electron microscopy. These results suggest that endotoxemia depresses cardiac mitochondrial respiration, an event related to the decrease in cardiac index. In contrast, cardiac function and mitochondrial respiration are maintained with PGI2 treatment.
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PMID:Myocardial protection with prostacyclin after lethal endotoxemia. 704 19

We investigated the changes of the inner-membrane components and the electron-transfer activities of bovine heart submitochondrial particles induced by the lipid peroxidation supported by NADPH in the presence of ADP-Fe3+. Most of the polyunsaturated fatty acids were lost as a result of the peroxidation, and phospholipids were changed to polar species. Ubiquinone was also modified to polar substances as the peroxidation proceeded. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis showed the disappearance of 27000-Mr and 30000-Mr proteins and the appearance of highly polymerized substances. Flavins and cytochromes were not diminished, but the respiratory activity was lost. The reactions of NADH oxidase and NADH-cytochrome c reductase were most sensitive to the peroxidation, followed by those of succinate oxidase and succinate-cytochrome c reductase. Succinate dehydrogenase and duroquinol-cytochrome c reductase were inactivated by more extensive peroxidation, but cytochrome c oxidase was only partially inactivated. NADH-ferricyanide reductase was not inactivated. The pattern of the inactivation indicated that the lipid peroxidation affected the electron transport intensively between NADH dehydrogenase and ubiquinone, and moderately at the succinate dehydrogenase step and between ubiquinone and cytochrome c.
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PMID:Alteration of inner-membrane components and damage to electron-transfer activities of bovine heart submitochondrial particles induced by NADPH-dependent lipid peroxidation. 708 19

It has been suggested that aromatic aldehydes may reduce cytochrome c [Wolf et al. Fedn Proc. 39 (3), 1013 (1980)]. Therefore, interaction of the aromatic aldehydes, p-anisaldehyde, benzaldehyde, p-tolualdehyde, p-carboxybenzaldehyde, p-chlorobenzaldehyde and p-nitrobenzaldehyde, with rat liver mitochondria was examined in vitro. Although both pyruvate/malate- and succinate-mediated respiration, as well as that mediated by other citric acid cycle intermediates, were inhibited by the aromatic aldehydes (0.5 to 1.0 mM), cytochrome c oxidase was not inhibited by aromatic aldehydes (1.0 to 20 mM). There was a marked inhibition of succinic dehydrogenase and both ADP- and DNP-stimulated respiration by benzaldehyde (2 to 20 mM). Since both pyruvate/malate- and succinate-mediated respiration were inhibited by the aromatic aldehydes without inhibition of cytochrome c oxidase, several sites of inhibition, possibly both at the site of transport of substrates and the active enzymes, may exist. Benzaldehyde, 300 microM, inhibited pyruvate/malate-mediated state 3 respiration by 50% which suggests that no additional functional group or metabolism to another species is required for these inhibitory effects.
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PMID:Interaction of aromatic aldehydes with isolated rat liver mitochondria. 711 22

Methylmalonic acid (MMA), which accumulates and is excreted in urine in mammals during vitamin B-12 deficiency, has been reported to inhibit succinate dehydrogenase, an enzyme involved in the mitochondrial tricarboxylic acid (TCA) cycle in rat liver. The enzyme inhibition by MMA may lead to various metabolic disorders as well as inhibition of mitochondrial energy generation in vitamin B-12-deficient mammals. To clarify the inhibition of succinate dehydrogenase by MMA in intact rat liver mitochondria, the effect of MMA on mitochondrial respiration was studied. When 6 mmol/L MMA was added to the reaction mixture for measuring mitochondrial respiration with succinate as a substrate, MMA was taken up and accumulated by the mitochondria (34-53 mmol/L). The accumulation of mitochondrial MMA was stimulated by the addition of ADP. Methylmalonic acid competitively inhibited State 3 mitochondrial respiration, and the Ki for the acid was 4.2 +/- 0.4 mmol/L. Although the respiratory control ratio decreased with increasing MMA concentration, the acid did not affect the phosphorus/oxygen ratio. Mitochondrial MMA accumulation secondary to vitamin B-12 deficiency inhibits succinate dehydrogenase and may contribute to various metabolic disorders associated with vitamin B-12 deficiency.
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PMID:Methylmalonic acid inhibits respiration in rat liver mitochondria. 747 65

Studies from our laboratory have shown that short-term ethanol exposure inhibits epidermal growth factor-dependent replication of cultured fetal rat hepatocytes, along with a drop in ATP level, and that these effects could be caused, at least in part, by ethanol-induced oxidative stress. In these prior studies, mitochondrial morphology was abnormal and membrane lipid peroxidation products were increased, along with reduced transmembrane potential and enhanced permeability to sucrose. To define the effects of ethanol on mitochondrial function further, the present study examines the impact of ethanol exposure on mitochondrial electron transport chain components. A 24-hr exposure of cultured fetal rat hepatocytes to ethanol (2.5 mg/ml) reduced mitochondrial complex I activity by 16% (p < 0.05), complex IV by 28% (p < 0.05), and succinate dehydrogenase by 23% (p < 0.05). This reduction was paralleled by lower ADP translocase activity (24%, p < 0.05) and diminished mitochondrial glutathione (GSH) (20%, p < 0.05). Pretreatment with 0.1 mM S-adenosyl methionine, before ethanol exposure, normalized mitochondrial GSH along with activities of complex I, complex IV, and succinate dehydrogenase. A 3-hr exposure of isolated mitochondria (which do not metabolize ethanol) to ethanol (2.5 mg/ml), inhibited the activities of complex I (19%, p < 0.05), complex IV (24%, p < 0.05), and of ATP synthesis (20%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of acute ethanol exposure on cultured fetal rat hepatocytes: relation to mitochondrial function. 769 41

Physiological increases in matrix calcium are known to stimulate three mitochondrial dehydrogenases. In mitochondria isolated from rat heart, calcium stimulates rates of State 3 respiration during oxidation of succinate and of several NAD-linked substrates. In this study, we investigated the effects of calcium on NADH dehydrogenase and succinate dehydrogenase activities since the mechanism of these effects is unresolved. The respiratory activities of intact mitochondria and submitochondrial particles (SMP) were compared during incubation in media containing either ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) or a Ca2+/EGTA buffer (approximately 1 microM free Ca2+). In intact mitochondria oxidizing 20 mM glutamate plus 2 mM malate, the membrane potential (delta psi) and matrix NAD(P)H were maintained at higher levels, and the maximal rate of ADP-stimulated respiration (State 3) was increased twofold by the presence of calcium. With succinate as substrate, calcium stimulated State 3 respiration but it did not influence the pyridine nucleotides redox state or membrane potential. Stimulation of succinate-supported respiration by addition of 6-10 microM ADP in the presence of hexokinase caused a sudden decrease in NAD(P)H and collapse of delta psi. This effect was not caused by inhibition of succinate dehydrogenase or by opening of the nonspecific pore. Calcium did not influence the oxidation of succinate by SMP containing either activated or nonactivated succinate dehydrogenase. In addition, calcium did not alter the kinetics of succinate dehydrogenase activation. Calcium and magnesium, in the concentration range of 0.02 to 5 mM, did not influence the NADH dehydrogenase activity of SMP. Energization of SMP by oligomycin addition, however, dramatically influenced the kinetic properties of NADH dehydrogenase. It is proposed that in heart mitochondria, calcium does not affect directly the components of electron transport but it may influence the activity of NADH dehydrogenase indirectly by increasing delta psi.
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PMID:Influence of calcium on NADH and succinate oxidation by rat heart submitochondrial particles. 786 38

Chloroquine causes an increase in phospholipid and a decrease in cholesterol in liver mitochondria. A significant decrease in the activities of mitochondrial inner membrane enzymes such as NADH dehydrogenase, succinate dehydrogenase and cytochrome c oxidase is observed. Decrease in cytochrome contents and respiratory control ratio, shown by a decrease in state 3(+ADP) and an increase in state 4 (-ADP), implies decreased ATP synthesis following chloroquine administration. The results confirm drug-induced inhibition of mitochondrial respiration, thereby impairing availability and utilisation of energy.
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PMID:Effect of chloroquine on rat liver mitochondria. 789 9

The toxicity of hydrophilic (cholate) and lipophilic (deoxycholate, chenodeoxycholate, and lithocholate) bile acids on the function of the electron transport chain was investigated in intact and disrupted rat liver mitochondria. In intact mitochondria, lipophilic bile acids used at a concentration of 100 mumol/L (0.1 mumol/mg protein) inhibited state 3 and state 3u (dinitrophenol-uncoupled) oxidation rates for L-glutamate, succinate, duroquinol or ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine as substrates. In contrast, state 4 oxidation rates and ADP/oxygen ratios were not significantly affected. At a bile acid concentration of 10 mumol/L (0.01 mumol/mg protein), the state 3 oxidation rate for L-glutamate was decreased in the presence of deoxycholate, chenodeoxycholate or lithocholate, whereas only lithocholate inhibited state 3 oxidation for succinate or duroquinol. In broken mitochondria, inhibition of oxidative metabolism was found for NADH or duroquinol as substrate in the presence of 100 mumol/L lithocholate (0.2 mumol/mg protein) and for duroquinol in the presence of 100 mumol/L chenodeoxycholate. Direct assessment of the activities of the enzyme complexes of the electron transport chain revealed decreased activities of complex I and complex III in the presence of 100 mumol/L deoxycholate or chenodeoxycholate or 10 mumol/L lithocholate. Inhibition of complex IV required higher bile acid concentrations (300 mumol/L for chenodeoxycholate or 30 mumol/L for lithocholate), and complex II was not affected. Both chenodeoxycholate and lithocholate were incorporated into mitochondrial membranes. The phospholipid content of mitochondrial membranes decreased in incubations containing 100 mumol/L (0.1 mumol/mg protein) chenodeoxycholate but was not affected in the presence of 100 mumol/L lithocholate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria. 790 81

The respiratory chain of adult Paragonimus westermani, a lung fluke, was characterized in isolated mitochondria. The fluke mitochondria exhibited cyanide- and antimycin A-sensitive succinate oxidase activity at a rate of 16.8 nmol O2 min-1 mg-1 protein. The succinate oxidation was shown to be stimulated by ADP and linked to the formation of membrane potential. The specific activities of oxidoreductases composing the succinate oxidase system, i.e., succinate-ubiquinone and succinate--cytochrome c oxidoreductase (complex II and complex II-III, respectively) and cytochrome c oxidase (complex IV), were compared in mitochondria from adult Paragonimus, bovine heart (an aerobic tissue), and muscle of adult Ascaris suum which possesses an anaerobic respiratory chain. The activity values of complex II-III and complex IV were high, middle, and low for bovine heart, Paragonimus, and A. suum, respectively, whereas the activity of complex II was comparable among the three sources. The cytochrome contents of Paragonimus mitochondria as determined by difference absorption spectrophotometry ranged between those in Ascaris and bovine mitochondria for types c and aa3 cytochromes. Paragonimus mitochondria exhibited a high activity of NADH-fumarate reductase; the specific activity was about 18-fold higher in fluke submitochondria than in bovine heart submitochondria. Quinone analysis by HPLC and mass spectrometry showed that the fluke mitochondria contain both rhodoquinone-10 and ubiquinone-10 at concentrations of 0.572 and 0.321 nmol mg-1 mitochondrial protein, respectively. These data clearly show that mitochondria from adult P. westermani, unlike adult Ascaris mitochondria, possess both cyanide-sensitive succinate oxidase and NADH-fumarate reductase systems, indicating that the fluke mitochondria are facultatively anaerobic.
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PMID:Respiratory chain of the lung fluke Paragonimus westermani: facultative anaerobic mitochondria. 803 Nov 21

Significant increase of liver succinic dehydrogenase (SDH, EC 1.3.99.1) activity was produced by carrageenin-induced edema in rats. Pretreatment with human placental extract inhibited the increased liver SDH activity in a dose-dependent manner. Placental extract was found to have little or no effect on the liver SDH activity in normal rats. Furthermore, heat-induced erythrocyte lysis was inhibited to a substantial extent by the extract and was found to be dose-responsive. However, adenosine diphosphate (ADP)-induced platelet aggregation and trypsin activity were not changed by the placental extract in vitro. The study indicates that the membrane stabilization and depletion of adenosine triphosphate (ATP) synthesis may contribute to antiinflammatory effect of the extract.
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PMID:Role of human placental extract on succinic dehydrogenase activity in carrageenin-induced edema in rats in vivo and its effect on erythrocyte lysis, platelet aggregation and trypsin activity in vitro. 806 56


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