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)

A carrier protein mediating alanine transport was purified from the membranes of the thermophilic bacterium PS3, by ion exchange chromatography in the presence of both Triton X-100 and urea. The alanine carrier was recovered in the nonadsorbed fraction from either DEAE- or CM-cellulose columns, suggesting that its isoelectric point was in the neutral pH region. The final preparation contained virtually no electron transfer components, ATPase, or NADH dehydrogenase. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed that the final preparation consisted of two major protein components with molecular weights of 36,000 and 9,400. Active transport of alanine after incorporation of the alanine carrier into reconstituted proteoliposomes was driven not only by an artificial membrane potential generated by potassium ion diffusion via valinomycin but also by mitochondrial cytochrome oxidase incorporated into the same liposomes and supplemented with both cytochrome c and ascorbic acid. The membrane-integrated portion (TFo) of the ATPase complex uncoupled alanine transport by conducting protons across the membrane.
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PMID:Isolation of the alanine carrier from the membranes of a thermophilic bacterium and its reconstitution into vesicles capable of transport. 19 18

The consumption of glucose by trypanosomatid protozoa such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., and Crithidia spp. is characterized by the excretion of reduced products such as succinate, pyruvate, ethanol, L-alanine, or lactate (depending on the species) not only in anaerobiosis, but also under aerobic conditions. The "aerobic fermentation" of glucose is accompanied by a complete lack, or even a reversal, of the Pasteur effect. This peculiar catabolism is mediated by a so-far unique compartmentation of the glycolytic enzymes, most of which are placed in an organelle called the glycosome; by an almost complete lack of inhibitory controls at the level of hexokinase and phosphofructokinase; and by a central role of CO2 fixation through the reaction catalyzed by phosphoenolpyruvate carboxykinase. The production of fermentative products seems to be due to a relative inefficiency of the respiratory chain, which lacks NADH dehydrogenase and the first phosphorylation site and preferentially uses succinate as substrate.
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PMID:Aerobic fermentation of glucose by trypanosomatids. 139 37

FNR is an iron-binding transcriptional regulator for anaerobic gene expression in Escherichia coli. Footprinting studies with the purified protein have confirmed that it is a site-specific DNA-binding protein. Transcription tests with the positively-regulated FFmelR promoter and the negatively-regulated ndh promoter likewise demonstrated that FNR can activate or repress transcription in vitro. Reducing conditions were not required but activity was abolished by substituting an essential cysteine residue with alanine (C122A) and the affinity for DNA was reduced by iron-depletion. The start point(s) for transcription of the FNR-repressed NADH dehydrogenase II gene (ndh) were identified by transcript mapping and the corresponding promoter (-35 and -10 sequences) was located immediately downstream of the FNR-binding site.
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PMID:FNR activates and represses transcription in vitro. 168 45

We characterized the genes in the regions of large inverted repeats (IRA and IRB, 10,058 base-pairs each) and a small single copy (SSC 19,813 bp) of chloroplast DNA from Marchantia polymorpha. The inverted repeat (IR) regions contain genes for four ribosomal RNAs (16 S, 23 S, 4.5 S and 5 S rRNAs) and five transfer RNAs (valine tRNA(GAC), isoleucine tRNA(GAU), alanine tRNA(UGC), arginine tRNA(ACG) and asparagine tRNA(GUU)). The gene organization of the IR regions in the liverwort chloroplast genome is conserved, although the IR regions are smaller (10,058 base-pairs) than any reported in higher plant chloroplasts. The small single-copy region (19,813 base-pairs) encoded genes for 17 open reading frames, a leucine tRNA(UAG) and a proline tRNA(GGG)-like sequence. We identified 12 open reading frames by homology of their coding sequences to a 4Fe-4S-type ferredoxin protein, a bacterial nitrogenase reductase component (Fe-protein), five human mitochondrial components of NADH dehydrogenase (ND1, ND4, ND4L, ND5 and ND6), two Escherichia coli ribosomal proteins (S15 and L21), two putative proteins encoded in the kinetoplast maxicircle DNA of Leishmania tarentolae (LtORF 3 and LtORF 4), and a bacterial permease inner membrane component (encoded by malF in E. coli or hisQ in Salmonella typhimurium).
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PMID:Structure and organization of Marchantia polymorpha chloroplast genome. IV. Inverted repeat and small single copy regions. 319 37

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

In order to identify the ligand residues of the [2Fe-2S] cluster of the 25 kDa (NQO2) subunit of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans, we mutated individually all seven cysteine residues (C61, C96, C101, C104, C113, C137, and C141) and one conserved histidine residue (H92) to Ser or Ala and expressed them in E. coli. After purification of the mutated 25 kDa subunits, the effect of mutations on the iron-sulfur cluster were characterized by chemical analyses and UV-visible and EPR spectroscopy. All mutated subunits, especially mutants of conserved cysteines, contained lower amounts of non-heme iron than wild-type. The subunits of three non-conserved cysteine residues (C61, C104, and C113) mutated to Ser and a histidine residue (H92) mutated to Ala exhibited essentially the same spectroscopic properties as those of the wild-type subunit. In contrast, mutation of the four conserved cysteine residues (C96, C101, C137, and C141) to Ser or Ala considerably altered the UV-visible and EPR spectra from the wild-type subunit. These results indicate that the four conserved cysteine residues coordinate the [2Fe-2S] cluster in the P. denitrificans 25 kDa subunit.
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PMID:Identification of amino acid residues associated with the [2Fe-2S] cluster of the 25 kDa (NQO2) subunit of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans. 795 17

Epimastigotes of Trypanosoma cruzi, the causative agent of Chagas disease, catabolize proteins and amino acids with production of MH3, and glucose with production of reduced catabolites, chiefly succinate and L-alanine, even under aerobic conditions. This "aerobic fermentation of glucose" is probably due to both the presence of low levels of some cytochromes, causing a relative inefficiency of the respiratory chain for NADH, reoxidation during active glucose catabolism, and the lack of NADH dehydrogenase and phosphorylation site I, resulting in the entry of reduction equivalents into the chain mostly as succinate. Phosphoenol pyruvate carboxykinase and pyruvate kinase may play an essential role in diverting glucose carbon to succinate or L-alanine, and L-malate seems to be the major metabolite for the transport of glucose carbon and reduction equivalents between glycosome and mitochondrion. The parasite contains proteinase and peptidase activities. The major lysosomal cysteine proteinase, cruzipain, has been characterized in considerable detail, and might be involved in the host/parasite relationship, in addition to its obvious role in parasite nutrition. Among the enzymes of amino acid catabolism, two glutamate dehydrogenases (one NADP- and the other NAD-linked), alanine aminotransferase, and the major enzymes of aromatic amino acid catabolism (tyrosine aminotransferase and aromatic alpha-hydroxy acid dehydrogenase), have been characterized and proposed to be involved in the reoxidation of glycolytic NADH.
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PMID:Intermediate metabolism in Trypanosoma cruzi. 805 82

We isolated and characterized mutants defective in nuo, encoding NADH dehydrogenase I, the multisubunit complex homologous to eucaryotic mitochondrial complex I. By Southern hybridization and/or sequence analysis, we characterized three distinct mutations: a polar insertion designated nuoG::Tn10-1, a nonpolar insertion designated nuoF::Km-1, and a large deletion designated delta(nuoFGHIJKL)-1. Cells carrying any of these three mutations exhibited identical phenotypes. Each mutant exhibited reduced NADH oxidase activity, grew poorly on minimal salts medium containing acetate as the sole carbon source, and failed to produce the inner, L-aspartate chemotactic band on tryptone swarm plates. During exponential growth in tryptone broth, nuo mutants grew as rapidly as wild-type cells and excreted similar amounts of acetate into the medium. As they began the transition to stationary phase, in contrast to wild-type cells, the mutant cells abruptly slowed their growth and continued to excrete acetate. The growth defect was entirely suppressed by L-serine or D-pyruvate, partially suppressed by alpha-ketoglutarate or acetate, and not suppressed by L-aspartate or L-glutamate. We extended these studies, analyzing the sequential consumption of amino acids by both wild-type and nuo mutant cells growing in tryptone broth. During the lag and exponential phases, both wild-type and mutant cells consumed, in order, L-serine and L-aspartate. As they began the transition to stationary phase, both cell types consumed L-tryptophan. Whereas wild-type cells then consumed L-glutamate, glycine, L-threonine, and L-alanine, mutant cells utilized these amino acids poorly. We propose that cells defective for NADH dehydrogenase I exhibit all these phenotypes, because large NADH/NAD+ ratios inhibit certain tricarboxylic acid cycle enzymes, e.g., citrate synthase and malate dehydrogenase.
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PMID:Mutations in NADH:ubiquinone oxidoreductase of Escherichia coli affect growth on mixed amino acids. 815 82

A heteroplasmic G-to-A transition at nucleotide pair (np) 14459 within the mitochondrial DNA (mtDNA)-encoded NADH dehydrogenase subunit 6 (ND6) gene has been identified as the cause of Leber hereditary optic neuropathy (LHON) and/or pediatric-onset dystonia in three unrelated families. This ND6 np 14459 mutation changes a moderately conserved alanine to a valine at amino acid position 72 of the ND6 protein. Enzymologic analysis of mitochondrial NADH dehydrogenase (complex I) with submitochondrial particles isolated from Epstein-Barr virus-transformed lymphoblasts revealed a 60% reduction (P < 0.005) of complex I-specific activity in patient cell lines compared with controls, with no differences in enzymatic activity for complexes II plus III, III and IV. This biochemical defect was assigned to the ND6 np 14459 mutation by using transmitochondrial cybrids in which patient Epstein-Barr virus-transformed lymphoblast cell lines were enucleated and the cytoplasts were fused to a mtDNA-deficient (p 0) lymphoblastoid recipient cell line. Cybrids harboring the np 14459 mutation exhibited a 39% reduction (p < 0.02) in complex I-specific activity relative to wild-type cybrid lines but normal activity for the other complexes. Kinetic analysis of the np 14459 mutant complex I revealed that the Vmax of the enzyme was reduced while the Km remained the same as that of wild type. Furthermore, specific activity was inhibited by increasing concentrations of the reduced coenzyme Q analog decylubiquinol. These observations suggest that the np 14459 mutation may alter the coenzyme Q-binding site of complex I.
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PMID:Use of transmitochondrial cybrids to assign a complex I defect to the mitochondrial DNA-encoded NADH dehydrogenase subunit 6 gene mutation at nucleotide pair 14459 that causes Leber hereditary optic neuropathy and dystonia. 862 78

The legume Vicia sativa (common vetch) harbors the neurotoxic nonprotein amino acid beta-cyano-L-alanine (BCLA) and its gamma-glutamyl derivative. BCLA elicits hyperexcitability, convulsions, and rigidity in chicks and rats after oral or intraperitoneal administration, but the mechanism of its action is unknown. The effect of different concentrations of BCLA (0.075-10.0 mM) has been investigated in an organotypic tissue culture system. BCLA concentrations of 0.075 and 0.60 mM had no effect, even up to 6 hr. No changes were observed in cultures treated with 1 mM BCLA for 4 hr. BCLA (2.0-10.0 mM) induces concentration-dependent changes in the explants. The explants display neurona vacuolation, chromatin, clumping, and dense shrunken cells, a pathological response generally seen with excitotoxin. MK-801 (35 microM), which blocks the open ion channel associated with the N-methyl-D-aspartate (NMDA) class of glutamate receptors, attenuates the neurotoxic property of BCLA, while the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (10-20 microM), provides no significant protection. Treatment of isolated mouse brain mitochondria with up to 5 mM BCLA had no inhibitory effect on the activity of NADH dehydrogenase (complex I) or cytochrome or oxidase (complex IV), a cyanide-sensitive enzyme. These results suggest that the neurotoxicity of BCLA (or derivative) is mediated directly or indirectly through NMDA receptors.
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PMID:beta-Cyano-L-alanine toxicity: evidence for the involvement of an excitotoxic mechanism. 902 49


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