Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.5 (NADH dehydrogenase)
 2,135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. With reference to the post-operative dysfunction of the liver observed after halothane anaesthesia, the effects of the anaesthetic on some metabolic functions were studied in the isolated perfused rat liver. Oxygen uptake, glycolysis, gluconeogenesis and urea synthesis were affected by halothane at a concentration (2.5% of the gas phase) within the range used in clinical anaesthesia. 2. At this concentration of halothane uptake of oxygen was inhibited in livers from both fed and starved rats. 3. In livers from fed rats there was a 16-fold increase in lactate production. This was accompanied by a fivefold decrease in the tissue content of 2-oxoglutarate and a more than twofold decrease in citrate. The calculated [free NAD(+)]/[free NADH] ratio in both cytoplasm and mitochondria was lower in the halothane-exposed livers than in controls. 4. In livers of starved rats the rate of gluconeogenesis from lactate was decreased by halothane to 30% of the control rate. 5. Halothane inhibited gluconeogenesis from alanine and propionate to the same extent as from lactate, whereas glucose formation from dihydroxyacetone, glycerol, fructose and sorbitol was relatively unaffected. 6. During gluconeogenesis from 10mm-lactate the tissue content of ATP was decreased by 50%, glutamate by 50% and 2-oxoglutarate was decreased eightfold in the halothane-exposed livers. 7. Halothane decreased urea synthesis in the presence of 10mm-NH(4)Cl and 2mm-ornithine to 15% of the control rate. 8. The inhibitions of gluconeogenesis and urea synthesis were completely abolished within 15min of withdrawal of the anaesthetic. 9. The stimulation of uptake of oxygen brought about by the addition of lactate or precursors of urea was abolished by halothane. 10. Effects on gluconeogenesis similar to those of halothane occurred in livers exposed to the anaesthetic methoxyflurane, although normal rates were not restored on withdrawal of the drug. Other anaesthetic agents tested (ketamine-HCl and trichloroethylene) decreased gluconeogenesis to 66% of the control rate. 11. The inhibitory effects of halothane are consistent with an interference at the stage of the NADH dehydrogenase of the electron-transport chain.
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PMID:The effects of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) on glycolysis and biosynthetic processes of the isolated perfused rat liver. 434 8

Submitochondrial particles from bovine heart in which NADH dehydrogenase is reduced by either addition of NADH and rotenone or by reversed electron transfer generate 0.9 +/- 0.1 nmol of O2-/min per mg of protein at pH 7.4 and at 30 degrees C. When NADH is used as substrate, rotenone, antimycin and cyanide increase O2- production. In NADH- and antimycin-supplemented submitochondrial particles, rotenone has a biphasic effect: it increases O2- production at the NADH dehydrogenase and it inhibits O2- production at the ubiquinone-cytochrome b site. The generation of O2- by the rotenone, the uncoupler carbonyl cyanide rho-trifluoromethoxyphenylhydrazone and oligomycin at concentrations similar to those required to inhibit energy-dependent succinate-NAD reductase. Cyanide did not affect O2- generation at the NADH dehydrogenase, but inhibited O2- production at the ubiquinone-cytochrome b site. Production of O2- at the NADH dehydrogenase is about 50% of the O2- generation but the ubiquinone-cytochrome b area at pH 7.4. Additivity of the two mitochondrial sites of O2- generation was observed over the pH range from 7.0 to 8.8. AN O2- -dependent autocatalytic process that requires NADH, submitochondrial particles and adrenaline is described.
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PMID:Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. 626 47

Cell-free extracts of methanol-grown Nocardia sp. 239 only show significant dye-linked methanol-oxidizing activity when NAD+ is added to the assay mixture. This activity resides in a multienzyme complex which could be resolved into 3 components, namely the methanol dehydrogenase, NAD-dependent aldehyde dehydrogenase and NADH dehydrogenase. In its dissociated form, the methanol dehydrogenase no longer shows dye reduction and although rises in the absorbance values around 340 nm are seen on addition of methanol plus NAD+ to the enzyme, this is not due to NADH production. However, dye reduction (NAD dependent) could be restored on incubating methanol dehydrogenase with the corresponding NADH dehydrogenase, obtained from the enzyme complex. It is concluded that this novel methanol dehydrogenase transfers the reducing equivalents, derived from methanol, directly to its associated NADH dehydrogenase via a mechanism in which NAD+ and PQQ are involved.
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PMID:NAD-dependent, PQQ-containing methanol dehydrogenase: a bacterial dehydrogenase in a multienzyme complex. 637 62

Stimulation of the rates of NAD(P)H oxidation, superoxide generation, and hydrogen peroxide formation by three anthracenedione antineoplastic agents in the presence of NADPH-cytochrome P-450 reductase, NADH dehydrogenase, or rabbit hepatic microsomes was studied and the results compared with those obtained for the anthracyclines Adriamycin and daunorubicin. In all cases the anthracenediones, including mitoxantrone and ametantrone, were significantly (5- to 20-fold) less effective than the anthracyclines in stimulating NAD(P)H oxidation, superoxide formation, or hydrogen peroxide production. Of the three anthracenediones studied, the ring-monohydroxylated compound showed the greatest activity followed by the ring-dihydroxylated derivative (mitoxantrone). In contrast, the non-ring-hydroxylated anthracenedione (ametantrone) was a relatively ineffective electron acceptor and inhibited the reduction of more effective acceptors such as Adriamycin. Michaelis-Menten kinetic constants were determined by analysis of the rates of NADPH oxidation. NADP+ and 2'-AMP inhibited the reduction of the ring-hydroxylated anthracenediones and anthracyclines, demonstrating the enzymatic nature of the reaction. The non-ring-hydroxylated anthracenedione inhibited the reduction of Adriamycin by both P-450 reductase and NADH dehydrogenase with 50% inhibition achieved at approximately 300 microM. Thus, there appears to exist a structural relationship between anthracenedione ring hydroxylation and metabolic activation. These results also suggest that the relative inability of the anthracenediones to function as artificial electron acceptors in comparison to the anthracyclines may be correlated with diminished anthracenedione cardiotoxicity.
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PMID:Bis(alkylamino)anthracenedione antineoplastic agent metabolic activation by NADPH-cytochrome P-450 reductase and NADH dehydrogenase: diminished activity relative to anthracyclines. 640 91

Incubation of Complex I (NADH-CoQ reductase) of ox heart mitochondria at 4 degrees C in the presence of 0.5 M NaClO4 followed by ammonium sulfate fractionation of the solubilized proteins results in the isolation of a resolved preparation still capable of catalyzing NADH-NAD+ transhydrogenation but having only low levels of NADH dehydrogenase activity. A number of NAD(H) analogues, including the photoaffinity probes, arylazido-beta-alanyl NAD+ (A3'-O-[3-[N-(4-azido-2-nitrophenyl)amino]propionyl]NAD+ and arylazido-beta-alanyl AcPyAD+ (A3'-O-[3-[N-(4-azido-2-nitrophenyl)amino]propionyl]AcPyAD+ can be utilized as substrates for transhydrogenation in this preparation. A further incubation (10 min) of the resolved NADH-NAD+ transhydrogenase in the presence of 0.5 M NaClO4, but now at 30 degrees C, results in the complete loss of this transhydrogenase activity. Photoaffinity labeling experiments utilizing arylazido-[3-3H]beta-alanyl NAD+ and arylazido-[3-3H]beta-alanyl AcPyAD+ with the resolved NADH-NAD+ transhydrogenase preparation prior to and following NaClO4 (30 degrees C) treatment indicates that the 42,000 molecular weight component of Complex I is the pyridine nucleotide binding site responsible for the major NADH-NAD+ (DD) transhydrogenase activity of Complex I.
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PMID:Identification of the NADH-NAD+ transhydrogenase peptide of the mitochondrial NADH-CoQ reductase (Complex I). A photodependent labeling study utilizing arylazido-beta-alanyl NAD+. 642 85

Extracellularly applied NADH, but not NAD or NADPH, increases the resting membrane potential from -74.1 to -76.6 mV in freshly isolated muscles in the presence of K+ in the incubation medium and from -64.6 to -72.9 mV in muscles equilibrated for 4-6 h in a K+-free solution. The NADH-induced hyperpolarization is blocked by pretreatment of muscles with ouabain, and the inhibitors of plasma membrane NADH dehydrogenase (adriamycin, azide, PCMB, atebrine, DIDS and bleomycin). The effect of NADH is accompanied by the disappearance of NADH from the incubation medium and by decreased membrane resistance. We conclude that NADH hyperpolarization is due to the enhancement of passive membrane permeability, apparently for K+, which might result from the conformational changes in the plasma membrane during the NADH dehydrogenase reaction. The possibility is discussed that NADH dehydrogenase mediates transport of K+ out from the cell using a pathway connected with the transmembrane Na+/K+ pump.
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PMID:Hyperpolarization of mouse skeletal muscle plasma membrane induced by extracellular NADH. 646 61

A soluble NADH dehydrogenase (NADH:ferricyanide oxidoreductase) has been obtained by simple disruption of cells of Thermus aquaticus strain T351, and purified. The enzyme is of low molecular mass, 50 000 Da, and displays many of the properties of the membrane-bound enzyme, including inhibition by both NADH and ferricyanide, and the same Km for ferricyanide. The enzyme contains 0.05 mol of FMN, 0.16 mol of labile sulphur and 2.2 mol of iron per mol of protein. The enzyme is inhibited by NAD and cupferron competitively with ferricyanide, and by ATP (but not ADP) competitively with NADH. The enzyme is particularly thermostable, having a half-life at 95 degrees C of 35 min. The effect of temperature on the molar absorption coefficient and the stability of NADH was determined.
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PMID:A soluble NADH dehydrogenase (NADH: ferricyanide oxidoreductase) from Thermus aquaticus strain T351. 684 28

This paper presents biochemical data upon a young male with a mitochondrial myopathy characterised by weakness, severe exercise intolerance, muscle wasting and exercise-induced lactic acidaemia. Two similar cases have been previously documented (Morgan-Hughes et al. 1979). This report more precisely locates the mitochondrial defect. In vitro mitochondrial studies show markedly decreased respiratory rates with all NAD-linked substrates whilst that with flavin-linked succinate is normal. Oxidative phosphorylation is normally coupled. Mitochondrial cytochrome components as determined by low temperature spectroscopy are normal. NADH-ferricyanide reductase and primary dehydrogenase activities are present at levels far in excess of that required to support normal NAD-linked substrate oxidation rates. Intramitochondrial NAD levels are similar to those found in other mammalian muscle. It is proposed therefore that the mitochondrial defect is situated between NADH dehydrogenase and the CoQ--Cytochrome b complex; possibly being a derangement of a non-haem iron sulphur centre.
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PMID:Mitochondrial myopathy. Biochemical studies revealing a deficiency of NADH--cytochrome b reductase activity. 722 53

The interaction of xanthomegnin, a quinone pigment, with the mitochondrial respiratory chain was demonstrated. Xanthomegnin was reduced by succinate, in the presence of submitochondrial particles or mitochondria, only after all oxygen had been consumed in the system, and the reduction was inhibited by antimycin A or KCN. Xanthomegnin was immediately reduced by NADH in a similar system, the reduced xanthomegnin was reoxidized by oxygen but the reduction by NADH was not inhibited by antimycin A or KCN. Xanthomegnin was also immediately reduced by NADH catalyzed by a purified particulate NADH dehydrogenase complex showing a molar ratio of 2 moles NADH for one mole of xanthomegnin. Reoxidation of the reduced pigment by oxygen occurred in this system. Oxygen consumption was accelerated when xanthomegnin was added to a reaction medium containing NADH, NADH segment and cytochrome c oxidase. Subsequent addition of cytochrome c resulted in a further marked acceleration of oxygen consumption. These results suggest that xanthomegnin interacts with the NAD-linked respiratory chain to produce a xanthomegnin shunt, but this does not occur with the succinate-linked chain.
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PMID:The interaction of a quinone pigment, xanthomegnin, with the mitochondrial respiratory chain. 726 94

Isoniazid (INH) interacts with nicotinamide adenine dinucleotide (NAD+) in the regulation of reduced NAD (NADH) oxidation in electron transport particles from Mycobacterium phlei. the interaction was shown to be at the level of the NADH dehydrogenase by the use of menadione as an artificial electron acceptor. Binding studies indicated that INH and NAD+ did not compete for a common regulatory site. Unlabeled INH was unable to displace [14C]NAD+ from electron transport particles, and unlabeled NAD+ could not remove [3H]INH from particles. Preincubation of electron transport particles with unlabeled INH did not prevent the subsequent binding of [14C]NAD+, and unlabeled NAD+ did not block the binding of [3H]INH. [14C]NAD+ binding to electron transport particles was specific and reversible. Unlabeled NAD+ could both displace and prevent the binding of labeled nucleotide. Binding of [14C]NAD+ to electron transport particles was proportional to the incubation concentration of label, and NAD+ stimulation of NADH oxidase activity was related to the amount of NAD+ bound to electron transport particles. [3H]INH was irreversibly bound to electron transport particles. INH and NAD+, although operating at the same level of the electron transport chain, did not appear to compete for the same regulatory site.
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PMID:Site of action of isoniazid on the electron transport chain and its relationship to nicotinamide adenine dinucleotide regulation in Mycobacterium phlei. 742 5


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