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:1.6.99.5 (NADH dehydrogenase)
2,135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently shown that exposure of Chinese hamster ovary (CHO) cells to a toxic dose of normobaric hyperoxia (98% O2 for 3 days) caused a disturbance of cellular energy metabolism, that is, respiratory failure followed by stimulation of glycolytic activity and a net depletion of ATP. Respiratory failure was correlated with a selective inactivation of three mitochondrial enzymes, that is, partial inactivation of NADH dehydrogenase and virtually complete inactivation of succinate and alpha-ketoglutarate dehydrogenase activities (Schoonen et al., 1990). To elucidate the biochemical basis of resistance to hyperoxia in a previously described oxygen-resistant substrain of Chinese hamster ovary (CHO) cells, we compared the resistant cells with wildtype CHO cells with respect to several key parameters of oxidative and glycolytic energy metabolism. The two cell types were critically different in that the succinate and alpha-ketoglutarate dehydrogenases of the oxygen-resistant cells were relatively resistant to inactivation by hyperoxia, which may at least partly explain their enhanced capacity to respire and survive under hyperoxic conditions. Although the biochemical basis for the observed enzyme resistance to hyperoxic inactivation remains to be elucidated, the present data underscore the importance of succinate and alpha-ketoglutarate dehydrogenases as critical targets in hyperoxic killing of wildtype CHO cells.
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PMID:Characterization of oxygen-resistant Chinese hamster ovary cells. III. Relative resistance of succinate and alpha-ketoglutarate dehydrogenases to hyperoxic inactivation. 201 73

Continuous exposure of Chinese hamster ovary (CHO) cells to an atmosphere of 98% O2, 2% CO2 (normobaric hyperoxia) leads within a period of several days to cytostasis and clonogenic cell death. Here we report respiratory failure as an important early symptom of oxygen intoxication in CHO cells, resulting in a more than 80% inhibition of oxygen consumption within 3 days of hyperoxic exposure. This inhibition appeared to be correlated with selective inactivation of three mitochondrial key enzymes, NADH dehydrogenase, succinate dehydrogenase, and alpha-ketoglutarate dehydrogenase. The latter enzyme controls the influx of glutamate into the Krebs cycle and is particularly critical for oxidative ATP generation in most cultured cells, which depends on exogenous glutamine rather than glucose as a carbon source. As expected, the inactivation of alpha-ketoglutarate dehydrogenase was correlated with a fall in cellular glutamine utilization, which became apparent from the first day of hyperoxic exposure. Thereafter, glucose utilization and lactate excretion started to increase, up to 3-fold, indicating a cellular response to respiratory failure aimed at increased ATP generation from glycolysis. However, in spite of this response, the cellular ATP level progressively decreased, up to 2.5-fold. Thus, killing of CHO cells by normobaric hyperoxia seems to be due to a severe disturbance of mitochondrial metabolism eventually leading to a depletion of cellular ATP pools.
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PMID:Respiratory failure and stimulation of glycolysis in Chinese hamster ovary cells exposed to normobaric hyperoxia. 235 58

A rapid decrease in male fertility in laboratory animals exposed to 1,2-dibromo-3-chloropropane (DBCP) has been suggested to be due, in part, to a postglycolytic inhibition of sperm carbohydrate metabolism. The present studies were performed to identify the specific site of DBCP-induced inhibition of intermediary metabolism. 14CO2 generation by epididymal sperm, isolated from Fischer 344 rats, was measured using radiolabeled tricarboxylic acid (TCA) cycle intermediates: acetyl CoA, citrate, alpha-ketoglutarate, and succinate. There was 0-28% inhibition of CO2 generation after addition of 0.5 mM DBCP and 81-98% inhibition with 3 mM DBCP, with all four substrates. The activities of alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, malate dehydrogenase, and lactate dehydrogenase were not inhibited by DBCP. Since the DBCP-induced inhibition of metabolism of different substrates to CO2 was similar, and since DBCP did not inhibit enzyme activities of glycolysis or the TCA cycle, a common site of inhibition was suspected. In evaluations of mitochondrial electron transport chain activity, DBCP (3 mM) inhibited oxygen consumption resulting from metabolism of endogenous substrates plus alpha-ketoglutarate or malate by about 80%. When succinate, an FAD-dependent oxidation, was used as a substrate, oxygen consumption was not inhibited by DBCP. It is concluded that DBCP inhibits sperm carbohydrate metabolism at the NADH dehydrogenase step in the mitochondrial electron transport chain.
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PMID:A biochemical basis for 1,2-dibromo-3-chloropropane-induced male infertility: inhibition of sperm mitochondrial electron transport activity. 367 26

Rat liver mitochondria, stored with the energy-linked functions preserved or in aging conditions, were used to assay the activity of various enzymes during five days. The preservation of energy-linked functions was monitored by the respiratory control coefficient. ATPase, cytochrome oxidase and NADH dehydrogenase showed increased activity when the energy-linked functions were preserved. In aging conditions, cytochrome oxidase, NADH dehydrogenase and ATPase showed decreased activity. The ATPase activity increased only when mitochondria were stored in the presence of inhibitors of the electron transport chain. The activity of NADH oxidase did not change, and succinate oxidase and succinate dehydrogenase showed a small decrease in their activity. The enzymes of the matrix, alpha-ketoglutarate dehydrogenase, malate dehydrogenase and aspartate aminotransferase showed little decrease in activity under either of the conditions of storage. The total protein content decreased slightly under both conditions of storage. These results show that the activity of the enzymes analysed was maintained at reasonable levels, when the energy-linked functions of isolated mitochondria were preserved.
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PMID:Studies on rat liver mitochondria: 4. Enzyme activities in mitochondria preserved at 0-4 degrees C. 646 13

The effect of alpha-tocopherol pretreatment (6 mg/100 g body wt/day, orally for a period of 90 days) on mitochondrial electron transport in myocardial infarction induced by isoproterenol (20 mg/100 g body wt, subcutaneously for two days) was studied in rats. A significant decrease was observed in the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase and cytochrome oxidase in heart mitochondria of isoproterenol administered rats. The cytochrome content and the oxidation of succinate in state 3 and state 4 decreased significantly in the cardiac mitochondria treatment. In alpha-tocopherol pretreated rats, the activities of TCA cycle enzymes, concentration of cytochromes and the oxidation of succinate in state 3 and state 4 were retained at near normal values, following isoproterenol administration.
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PMID:Effect of alpha-tocopherol on mitochondrial electron transport in experimental myocardial infarction in rats. 975 71

Studies of respiration on glucose in procyclic Trypanosoma congolense in the presence of rotenone, antimycin, cyanide, salicylhydroxamic acid and malonate have indicated the presence of NADH dehydrogenase, cytochrome b-c1, cytochrome aa3, trypanosome alternate oxidase and NADH fumarate reductase/succinate dehydrogenase pathway that contributes electrons to coenzyme Q of the respiratory chain. The rotenone sensitive NADH dehydrogenase, the trypanosome alternate oxidase, and cytochrome aa3 accounted for 24.5 +/- 6.5, 36.2 +/- 4.2 and 54.1 +/- 5.5% respectively of the total respiration. Activities of lactate dehydrogenase, NAD(+)-linked malic enzyme and pyruvate kinase were less than 6 nanomoles/min/mg protein suggesting that they play a minor role in energy metabolism of the parasite. Phosphoenolpyruvate carboxykinase, pyruvate dehydrogenase, succinate dehydrogenase, NADP(+)-linked malic enzyme, NADH fumarate reductase, malate dehydrogenase, and alpha-ketoglutarate dehydrogenase and glycerol kinase on the other hand had specific activities greater than 60 nanomoles/min/mg protein. These enzyme activities could account for the production of pyruvate, acetate, succinate and glycerol. The results further show that the amount of glycerol produced was 35-48% of the combined total of pyruvate, acetate and succinate produced. It is apparent that some of the glycerol 3-phosphate produced in glycolysis in the presence of salicylhydroxamic acid is dephosphorylated to form glycerol while the rest is oxidised via cytochrome aa3 to form acetate, succinate and pyruvate.
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PMID:Pathways of glucose catabolism in procyclic Trypanosoma congolense. 1084 79

Aging is characterized by a general decline in physiological functions that affects many tissues and increases the risk of death. Deterioration of mitochondria, the major source and target of reactive oxygen species (ROS), is implicated in aging and a variety of age-related diseases. In the present study, the activities of citric acid cycle enzymes, such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase, were found to be decreased in aged rats as well as that of electron-transferring enzymes such as NADH dehydrogenase and cytochrome c oxidase. After supplementation of carnitine to aged rats, the activities of these enzymes reverted nearer to that of young control rats. These findings suggest that L-carnitine improves the activities of mitochondrial enzymes, increases the electron flow through the electron transport chain, and improves reducing equivalence, thereby improves energy status in aged rats.
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PMID:Supplementation of L-carnitine improves mitochondrial enzymes in heart and skeletal muscle of aged rats. 1584 73

Chronic exposure to cigarette smoke affects the structure and function of mitochondria, which may account for the pathogenesis of smoking-related diseases. Bacopa monniera Linn., used in traditional Indian medicine for various neurological disorders, was shown to possess mitrochondrial membrane-stabilizing properties in the rat brain during exposure to morphine. We investigated the protective effect of bacoside A, the active principle of Bacopa monniera, against mitochondrial dysfunction in rat brain induced by cigarette smoke. Male Wistar albino rats were exposed to cigarette smoke and administered bacoside A for a period of 12 weeks. The mitochondrial damage in the brain was assessed by examining the levels of lipid peroxides, cholesterol, phospholipid, cholesterol/phospholipid (C/P) ratio, and the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, and cytochrome C oxidase. The oxidative phosphorylation (rate of succinate oxidation, respiratory control ratio and ADP/O ratio, and the levels of ATP) was evaluated for the assessment of mitochondrial functional capacity. We found significantly elevated levels of lipid peroxides, cholesterol, and C/P ratio, and decreased levels of phospholipids and mitochondrial enzymes in the rats exposed to cigarette smoke. Measurement of oxidative phosphorylation revealed a marked depletion in all the variables studied. Administration of bacoside A prevented the structural and functional impairment of mitochondria upon exposure to cigarette smoke. From the results, we suggest that chronic cigarette smoke exposure induces damage to the mitochondria and that bacoside A protects the brain from this damage by maintaining the structural and functional integrity of the mitochondrial membrane.
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PMID:Protective effect of bacoside A on cigarette smoking-induced brain mitochondrial dysfunction in rats. 1605 Aug 6

The present study was aimed to examine the protective effects of Sargassum polycystum (Phaeophyceae) alcoholic extract on changes in liver mitochondrial enzymes against acetaminophen induced toxic hepatitis in experimental rats. The levels of protein, lipid peroxide, glutathione (GSH) in mitochondrial fraction, superoxide dismutase (SOD) and catalase (CAT) were also determined. The activities of tricarboxylic acid enzymes such as isocitrate dehydrogenase (ICD), alpha-ketoglutarate dehydrogenase (alpha-KGD), succinate dehydrogenase (SD), malate dehydrogenase (MD), NADH dehydrogenase, and cytochrome-c-oxidase were determined in mitochondrial fraction. The rats intoxicated with acetaminophen showed significant elevation in the levels of lipid peroxides with decreased levels of protein, GSH, SOD, CAT and impaired tricarboxylic acid cycle enzyme activities. The prior oral administration of S. polycystum alcoholic extract showed significant diminution in the severity of toxic hepatitis in acetaminophen-induced rats by maintaining the activities of tricarboxylic acid enzymes with concomitant improvement in the hepatic mitochondrial antiperoxidative status when compared with intoxicated animals. The results obtained in the present study indicate that the protective effects of S. polycystum extract may be due to the presence of some active compounds that are inhibitory against the free radicals generated during lipid peroxidation in acetaminophen induced toxic hepatitis.
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PMID:Antioxidant effect of Sargassum polycystum (Phaeophyceae) against acetaminophen induced changes in hepatic mitochondrial enzymes during toxic hepatitis. 1616 51

Disease caused by viruses, especially white spot syndrome virus (WSSV), present the greatest challenge to shrimp aquaculture worldwide. Massive tissue disintegration occurs in WSSV-infected ectodermal and mesodermal tissues of penaeid shrimp. The activities of membrane bound phosphatases (Na(+)K(+)ATPase, Ca(2+)ATPase, Mg(2+)ATPase and Total ATPase), transaminases (alanine transaminase (ALT) and aspartate transaminase (AST)) and mitochondrial enzymes (isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alpha-ketoglutarate dehydrogenase (KGDH), NADH dehydrogenase, cytochrome C oxidase) in WSSV-infected tissues (hemolymph, hepatopancreas, gills and muscle) of Fenneropenaeus indicus were determined at intervals after WSSV infection (0, 24, 48, 72 and after 72 h (moribund)). The activities of phosphatases, transaminases and mitochondrial enzymes in healthy as compared with WSSV-infected hemolymph, hepatopancreas, gills and muscle showed marked divergence throughout the course of infection. WSSV infected hemolymph, hepatopancreas, gills and muscle exhibited significantly reduced activity of membrane bound phosphatases compared with the uninfected animals. Inactivation of these enzymes may occur due to increased production of free radicals, that cause conformational change by oxidation of 'SH' groups present at the active site. Significantly marked elevation in the activities of transaminases (ALT and AST) was observed in WSSV-infected hemolymph, hepatopancreas, gills and muscle compared to the uninfected tissues. This may be due to leakage of these enzymes from the damaged tissues. The activities of mitochondrial enzymes in WSSV-infected tissues were significantly decreased compared to the activities in uninfected animals. WSSV-infected animals showed reduced feeding that may have led to decreased oxidation of glucose via the TCA cycle. Excessive production of free radicals in WSSV-infected animals may have affected aerobic oxidation leading to lower production of ATP. It is concluded that membrane dynamics play a major role in the pathogenesis of WSSV infection.
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PMID:Activities of membrane bound phosphatases, transaminases and mitochondrial enzymes in white spot syndrome virus infected tissues of Fenneropenaeus indicus. 1641 26


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