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)

The steady-state kinetics of the NADH dehydrogenase activities of the mitochondrial NADH-ubiquinone oxidoreductase in the presence of one-electron acceptors, ferricyanide and hexammineruthenium(III), were studied. Similar to ferricyanide, hexammineruthenium was found to be an efficient electron acceptor for the enzyme in inside-out submitochondrial particles and isolated Complex I, but not in intact mitochondria. Qualitatively the same results were obtained using submitochondrial particles or isolated Complex I. Both hexammineruthenium(III) and ferricyanide reduction was rotenone-insensitive and showed no stimulation by the uncouplers in tightly coupled submitochondrial particles. In contrast to the NADH-ferricyanide oxidoreductase reaction which exhibits a double substrate inhibition behaviour, no inhibition of the reaction by either NADH or the electron acceptor was revealed in the NADH-hexammineruthenium(III) reductase reaction. The double-reciprocal plots 1/v vs. 1/[NADH] at various hexammineruthenium(III) concentrations gave a series of straight lines intercepting in the third quadrant, thus supporting the mechanism of the overall reaction in which the reduced enzyme-NAD+ complex is oxidized by the electron acceptor before NAD+ dissociation. The apparent KsNADH values equal to 1 x 10(-5) and 4 x 10(-5) M for submitochondrial particles and Complex I, respectively (27 degrees C, pH 8.0), were determined from the secondary KmNADH vs. V (at different acceptor concentrations) plot. The Ki values for the competitive inhibition of NADH oxidation by NAD+ were 1 x 10(-3) M and 2 x 10(-3) M for the respective enzyme preparations. The results obtained suggest that hexammineruthenium(III) interacts with the NADH-ubiquinone oxidoreductase at a single reaction site different from that for fericyanide.
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PMID:Kinetics of the mitochondrial NADH-ubiquinone oxidoreductase interaction with hexammineruthenium(III). 844 12

Anaerobically grown Escherichia coli cells were shown to acidify the reaction medium in response to oxygen or dimethyl sulfoxide (DMSO) pulses, with the H+/e- stoichiometry being close to 2.5 and 1.5, respectively. In the presence of the NADH dehydrogenase I (NDH-I) inhibitor 8-methyl-N-vanillyl-6-nonenamide (capsaicin) or in mutants lacking NDH-I, this ratio decreased to 1 for O2 and to 0 for DMSO. These data suggest that (i) the H+/e- stoichiometry for E. coli NDH-I is at least 1.5 and (ii) the DMSO reductase does not generate a proton motive force.
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PMID:H+/e- stoichiometry for NADH dehydrogenase I and dimethyl sulfoxide reductase in anaerobically grown Escherichia coli cells. 889 24

The mitochondrial electron-transport chain present in the procyclic and long slender bloodstream forms of Trypanosoma brucei brucei was investigated by means of several experimental approaches. The oxidation of proline, glycerol and glucose in procyclic cells was inhibited 80-90% by antimycin A or cyanide, 15-19% by salicylhydroxamic acid, and 30-35% by rotenone. Cytochrom-c-reductase activity, with proline or glycerol 3-phosphate as substrate, in a mitochondrial fraction isolated from these cells was inhibited by antimycin and rotenone, but not by malonate, while cytochrome-c-reductase activity with succinate as substrate was inhibited by antimycin A and malonate, but not by rotenone. In addition, the reduction of dichloroindophenol by NADH was inhibited by rotenone but not by malonate, which suggests that rotenone-sensitive NADH dehydrogenase (complex I) is present in these mitochondria. The presence of three subunits of NADH dehydrogenase was observed in immunoblots of mitochondrial proteins with specific antibodies raised against peptides corresponding to predicted antigenic regions of these proteins, which provides further evidence for the presence of NADH dehydrogenase. In long slender bloodstream forms, the oxidation of glucose or glycerol was inhibited 100% by salicyhydroxamic acid, unaffected by cyanide or antimycin A, and inhibited 40% or 75%, respectively, by rotenone, which suggests that NADH dehydrogenase is present in these cells. In a mitochondrial fraction isolated from the bloodstream forms, oxygen uptake with glycerol 3-phosphate as substrate was inhibited 65% by rotenone. Low levels of rotenone-sensitive NADH-dependent reduction of dichloroindophenol and the presence of subunits 7 and 8 of NADH dehydrogenase provided additional evidence for the presence of NADH dehydrogenase in bloodstream forms of T. brucei.
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PMID:The presence of rotenone-sensitive NADH dehydrogenase in the long slender bloodstream and the procyclic forms of Trypanosoma brucei brucei. 894 79

The effect of administration of ethionine on rat liver mitochondrial functions and the protective effect of vitamin E on ethionine induced damage was studied. Ethionine treatment decreased the rate of respiration, respiratory control ratio and P/O ratio. There was a significant decrease in the activities of NADH dehydrogenase, succinate cytochrome C reductase and cytochrome oxidase. A significant decrease was seen on membrane potential and on the levels of ATP. Among the mitochondrial phospholipids only cardiolipin decreased significantly. The lipid peroxide level increased significantly in ethionine treated rats. Administration of vitamin E prior to ethionine treatment relieved the effects (induced by ethionine) on all the parameters studied. This study shows that vitamin E protects against ethionine toxicity.
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PMID:Protective effect of vitamin E against ethionine toxicity. 911 39

Adriamycin (or doxorubicin) is an active and broad spectrum chemotherapeutic agent. Unfortunately, its clinical use is severely restricted by a dose-limiting cardiotoxicity which has been linked to the formation of superoxide. Enzymatic one-electron reduction of adriamycin forms adriamycin semiquinone radical, which rapidly reacts with oxygen to form superoxide and adriamycin. In this way, adriamycin provides a kinetic mechanism for the one-electron reduction of oxygen by flavoenzymes such as NADPH-cytochrome P450 reductase and mitochondrial NADH dehydrogenase. We demonstrate here that the endothelial isoform of nitric oxide synthase (eNOS) reduces adriamycin to the semiquinone radical. As a consequence, superoxide formation is enhanced and nitric oxide production is decreased. Adriamycin binds to eNOS with a Km of approximately 5 microM, as calculated from both eNOS-dependent NADPH consumption and superoxide generation. Adriamycin stimulated superoxide formation is not affected by calcium/calmodulin and is abolished by the flavoenzyme inhibitor, diphenyleneiodonium. This strongly suggests that adriamycin undergoes reduction at the reductase domain of eNOS. A consequence of eNOS-mediated reductive activation of adriamycin is the disruption of the balance between nitric oxide and superoxide. This may lead eNOS to generate peroxynitrite and hydrogen peroxide, potent oxidants implicated in several vascular pathologies.
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PMID:Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. 933 25

The NDI1 gene encodes the internal rotenone-insensitive NADH-quinone oxidoreductase localized in the inner mitochondrial membranes of Saccharomyces cerevisiae. The T7 tag-fused mature NDI1 was overexpressed in Escherichia coli. The overexpressed NDI1 was exclusively found in the membrane fraction. The NDI1-overexpressed membranes showed significantly increased activities of NADH oxidase and NADH-ubiquinone-1 (UQ1) reductase when compared with the control membranes. Flavone, which is a specific inhibitor of the S. cerevisiae NDI1, inhibited almost completely NADH oxidase and NADH-UQ1 reductase activities of NDI1-overexpressed membranes but scarcely inhibited these activities of the control membranes. In addition, the NADH oxidase activity of the NDI1-overexpressed membranes was also inhibited by KCN as well as the control membranes. These results indicate that the overexpressed NDI1 worked as a member of the respiratory chain in the host cells, even though E. coli membranes are different from S. cerevisiae inner mitochondrial membranes in terms of quinones and lipid composition.
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PMID:Rotenone-insensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae mitochondria: the enzyme expressed in Escherichia coli acts as a member of the respiratory chain in the host cells. 946 35

Chlorophyll fluorescence measurements were performed on osmotically lysed potato chloroplasts in order to characterize the reactions involved in the dark reduction of photosynthetic inter-system chain electron carriers. Addition of NADH or NADPH to lysed chloroplasts increased the chlorophyll fluorescence level measured in the presence of a non-actinic light until reaching Fmax, thus indicating an increase in the redox state of the plastoquinone (PQ) pool. The fluorescence increase was more pronounced when the experiment was carried out under anaerobic conditions and was about 50% higher when NADH rather than NADPH was used as an electron donor. The NAD(P)H-PQ oxidoreductase reaction was inhibited by diphenylene iodonium, N-ethylmaleimide and dicoumarol, but insensitive to rotenone, antimycin A and piericidin A. By comparing the substrate specificity and the inhibitor sensitivity of this reaction to the properties of spinach ferredoxin-NADP+-reductase (FNR), we infer that FNR is not involved in the NAD(P)H-PQ oxidoreductase activity and conclude to the participation of rotenone-insensitive NAD(P)H-PQ oxidoreductase. By measuring light-dependent oxygen uptake in the presence of DCMU, methyl viologen and NADH or NADPH as an electron donors, the electron flow rate through the NAD(P)H-PQ oxidoreductase is estimated to about 160 nmol O2 min-1 mg-1 chlorophyll. The nature of this enzyme is discussed in relation to the existence of a thylakoidal NADH dehydrogenase complex encoded by plastidial ndh genes. Copyright 1998 Elsevier Science B.V.
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PMID:Reduction of the plastoquinone pool by exogenous NADH and NADPH in higher plant chloroplasts. Characterization of a NAD(P)H-plastoquinone oxidoreductase activity 952 46

The activities of the enzymes NADH dehydrogenase, NADH cytochrome e reductase, succinate dehydrogenase, succinate cytochrome e reductase, cytochrome c oxidase and citrate synthase in normal and sick human skeletal muscle mitochondria were determined. A control group was formed by 13 normal people and without using continuous medication. The patient group was formed by 10 people whose pathological diagnosis indicated suspicion of mitochondrial myopathy. A decrease in the activity of the enzymes in all patient was observed: 7 with abnormality in all the tested enzymes; 2 with deficiencies in all the enzymes except cytochrome e oxidase; and 1 with dysfunction only in the activities of succinate dehydrogenase and succinate cytochrome e reductase. The results indicate multiple or combined deficiencies in the respiratory chain, besides dysfunction of citrate synthase in 9 patients. In one exceptional case, the enzymatic deficiency was restricted to complex II. It is possible to conclude that the methodology used herein is adequate and easily applicable to clinical objectives, and that the results obtained allow characterization of the deficient mitochondrial enzymatic complexes, thus showing that the origin of the diseases is an energetic metabolic dysfunction.
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PMID:[Characterization of mitochondrial myopathies through the evaluation of the enzymatic activities involved in energy metabolism]. 962 85

The NADH oxidase of Amphibacillus xylanus shows high NADH-peroxide reductase activity for hydrogen peroxide and alkyl hydroperoxides in the presence of a 22-kDa disulfide-containing protein component (Y. Niimura, L. B. Poole, and V. Massey, J. Biol.Chem. 270, 25645-25650, 1995). It was found that the membrane-bound NADH dehydrogenase of an alkaliphilic Bacillus (YN-1) involved in the respiratory chain also exhibits reductase activity for hydrogen peroxide and cumene hydroperoxide in the presence of the 22-kDa component from Amphibacillus xylanus. Vmax values for these substrates were as high as those of the NADH oxidase of A. xylanus. Although the 38-kDa protein produced by trypsin treatment of NADH dehydrogenase retains NADH dehydrogenase activity, it exhibited no peroxide reductase activity in the presence of the 22-kDa component from A. xylanus. The NADH dehydrogenase of YN-1 might not only catalyze electron flow from NADH to the respiratory chain, but also function for scavenging peroxide.
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PMID:Peroxide reductase activity of NADH dehydrogenase of an alkaliphilic Bacillus in the presence of a 22-kDa protein component from Amphibacillus xylanus. 964 49

Isoniazid is the most widely used antituberculosis drug. Genetic studies in Mycobacterium smegmatis identified the inhA-encoded, NADH-dependent enoyl acyl carrier protein reductase as the primary target for this drug. A reactive form of isoniazid inhibits InhA by reacting with the NAD(H) cofactor bound to the enzyme active site forming a covalent adduct (isonicotinic acyl NADH) that is apt to bind with high affinity. Resistance can occur by increased expression of InhA or by mutations that lower the enzyme's affinity to NADH. Both of these resistance mechanisms are observed in 30% of clinical tuberculosis isolates. Mutation in katG, which encodes catalase peroxidase, is the most common source for resistance. Another mechanism for isoniazid resistance, in M. smegmatis, occurs by defects in NADH dehydrogenase (Ndh) of the respiratory chain. Genetic data indicated that ndh mutations confer resistance by lowering the rate of NADH oxidation and increasing the intracellular NADH/NAD+ ratio. An increased amount of NADH may prevent formation of isonicotinic acyl NADH or may promote displacement of the isonicotinic acyl NADH from InhA. While our studies have identified this mechanism in M. smegmatis, results reported in early literature lead us to believe that it can occur in Mycobacterium tuberculosis.
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PMID:Mechanisms for isoniazid action and resistance. 994 10


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