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)

Sonicated mitochondria catalyse the reduction of ferric salts, and the subsequent incorporation of Fe(2+) into haem, when provided with a reducing substrate such as succinate or NADH. The rate of haem synthesis was low under aerobic conditions and, after a short lag period, accelerated once anaerobic conditions were achieved; it was insensitive to antimycin A. The lag period was decreased by preincubating the mitochondria with NADH and Fe(3+). Newly formed Fe(2+) was autoxidized rapidly and the consequent O(2) uptake was measured with an oxygen electrode to determine the rate of enzymic formation of Fe(2+) from FeCl(3); this reaction was rapid in sonicated mitochondria provided with NADH or succinate and was insensitive to antimycin A. The reaction was very slow in intact mitochondria, suggesting a permeability barrier to Fe(3+) ions. This system was used to test the permeability of the mitochondrial membrane to various iron complexes of biological importance. Of the compounds tested only ferrioxamine G appeared to penetrate readily and the iron of this complex was reduced when intact mitochondria were supplied with succinate or NADH-linked substrates. The reduction was insensitive to rotenone or antimycin A. Both ferrioxamine G and ferrioxamine B were, however, reduced by particles. The membrane fraction of sonicated mitochondria was necessary for the reduction. The rate of ferrioxamine B reduction by sonicated mitochondria was measured by a dual-wavelength spectrophotometric assay and was found to be stimulated in conditions where the Fe(2+) produced was utilized for haem synthesis. The addition of FeCl(3) to anaerobic particles caused an oxidation of cytochrome b when this region of the respiratory chain was isolated by treatment with rotenone and antimycin A. These results suggest that the reduction of ferric iron and its complexes occurs inside the inner mitochondrial membrane in proximity to ferrochelatase. Possible sites for this reduction are the flavoproteins, succinate and NADH dehydrogenase.
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PMID:The utilization of iron and its complexes by mammalian mitochondria. 434 50

1. A spectroscopic resolution has been made of the components contributing to the ;iron-flavoprotein' trough extending from 450 to 520nm in the reduced-minus-oxidized difference spectrum of submitochondrial particles of Torulopsis utilis. 2. Seven components were identified other than cytochrome b, ubiquinone and succinate dehydrogenase. On the basis of the effects of iron- and sulphate-limited growth of cells on their subsequently derived electron-transport particles, and also by consideration of analytical measurements of the concentration of FMN, FAD, non-haem iron and acid-labile sulphide in the electron-transport particles in relation to the magnitude of the spectroscopic changes, it was possible to identify five of these components as follows: species 1a, the flavin of NADH dehydrogenase ferroflavoprotein; species 1b, the iron-sulphur component of NADH dehydrogenase ferroflavoprotein; species 1', the flavin of an NADPH dehydrogenase; species 2, an iron-sulphur or ferroflavoprotein component; species 3, the flavin of l-3-glycerophosphate dehydrogenase. Two additional components were a fluorescent flavoprotein, probably lipoamide dehydrogenase, and a b-type cytochrome reducible by NADH or NADPH but not reoxidizable by the respiratory chain. 3. Species 1b and 2 were undetectable in electron-transport particles from iron- or sulphate-limited cells, but could be recovered in vivo under non-growing conditions. 4. The recovery in vivo of species 2 but not species 1b was inhibited by cycloheximide. 5. The recovery of species 1b correlates with the recovery of site 1 conservation. 6. The recovery of species 1b with species 2 correlates with the recovery of piericidin A sensitivity. 7. Evidence is presented for an NADPH dehydrogenase distinct from NADH dehydrogenase. The oxidation of NADH and NADPH by the respiratory chain is sensitive to piericidin A, and an iron-sulphur protein common to both pathways (species 2) is suggested as the piericidin A-sensitive component. 8. The approximate E'(0) (pH7.0) values of species 1 (a and b, low potential) and species 2 (high potential) indicate that site 1 energy conservation occurs between the levels of species 1 (a and b) and species 2.
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PMID:Spectroscopic studies of flavoproteins and non-haem iron proteins of submitochondrial particles of Torulopsis utilis modified by iron- and sulphate-limited growth in continuous culture. 439 18

1. Rat liver mitochondria were separated on the basis of their sedimentation coefficients in an iso-osmotic gradient of Ficoll-sucrose by rate zonal centrifugation. The fractions (33, each of 40ml) were collected in order of decreasing density. Fractions were analysed by spectral analysis to determine any differences in the concentrations of the cytochromes and by enzyme analyses to ascertain any differences in the activities of NADH dehydrogenase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase. 2. When plotted as% of the highest specific concentration, the contents of cytochrome a+a(3) and cytochrome c+c(1) were constant in all fractions but cytochrome b was only 65% of its maximal concentration in fraction 7 and increased with subsequent fractions. As a result, the cytochrome b/cytochrome a+a(3) ratio almost doubled between fractions 7 and 25 whereas the cytochrome c+c(1)/cytochrome a+a(3) ratio was unchanged. 3. Expression of the dehydrogenase activities as% of highest specific activity showed the following for fractions 6-26: NADH dehydrogenase activity remained fairly constant in all fractions; succinate dehydrogenase activity was 62% in fraction 6 and increased steadily to its maximum in fraction 18 and then decreased; the activity of alpha-glycerophosphate dehydrogenase was only 53% in fraction 6 and increased slowly to its peak in fractions 22 and 24. 4. These differences did not result from damaged or fragmented mitochondria or from microsomal contamination. 5. These results demonstrate that isolated liver mitochondria are biochemically heterogeneous. The importance of using a system for separating biochemically different mitochondria in studies of mitochondrial biogenesis is discussed.
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PMID:Biochemical heterogeneity of rat liver mitochondria separated by rate zonal centrifugation. 467 5

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

The in vitro effects of PR toxin, a toxic secondary metabolite produced by certain strains of Penicillium roqueforti, on the membrane structure and function of rat liver mitochondria were investigated. It was found that the respiratory control and oxidative phosphorylation of the isolated mitochondria decreased concomitantly when the toxin was added to the assay system. The respiratory control ratio decreased about 60% and the ADP/O ratio decreased about 40% upon addition of 3.1 X 10(-5) M PR toxin to the highly coupled mitochondria. These findings suggest that PR toxin impairs the structural integrity of mitochondrial membranes. On the other hand, the toxin inhibited mitochondrial respiratory functions. It exhibited noncompetitive inhibitions to succinate oxidase, succinate-cytochrome c reductase, and succinate dehydrogenase activities of the mitochondrial respiratory chain. The inhibitory constants of PR toxin to these three enzyme systems were estimated to be 5.1 X 10(-6), 2.4 X 10(-5), and 5.2 X 10(-5) M, respectively. Moreover, PR toxin was found to change the spectral features of succinate-reduced cytochrome b and cytochrome c1 in succinate-cytochrome c reductase and inhibited the electron transfer between the two cytochromes. These observations indicate that the electron transfer function of succinate-cytochrome c reductase was perturbed by the toxin. However, PR toxin did not show significant inhibition of either cytochrome oxidase or NADH dehydrogenase activity of the mitochondria. It is thus concluded that PR toxin exerts its effect on the mitochondrial respiration and oxidative phosphorylation through action on the membrane and the succinate-cytochrome c reductase complex of the mitochondria.
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PMID:Biochemical effects of PR toxin on rat liver mitochondrial respiration and oxidative phosphorylation. 632 85

(1) The V1 (substrate-Q oxidoreductase activity) and V2 (QH2 oxidase activity) for the oxidation of substrates by submitochondrial particles have been measured by using heptylhydroxyquinoline N-oxide (HQNO) as inhibitor of V2. (2) Partial destruction of the Rieske Fe-S cluster by treatment with Bal (2,3-dimercaptopropanol) + O2 has the same effect on the QH2 oxidase activity as partial saturation of the antimycin-binding site with HQNO. (3) The extent of the rapid reduction of cytochrome b in the presence of excess antimycin is proportional to the percentage of intact Rieske Fe-S cluster. (4) The measured rate of oxidation of endogenous ubiquinol (V2) by submitochondrial particles is dependent on the substrate used to reduce ubiquinone, especially at low levels of ubiquinone. (5) Pool-function kinetics in the oxidation of substrate, found both in the presence and absence of free ubiquinone, are due both to the pool of free ubiquinone and to direct collision between Q-loaded Q-reducing and -oxidizing enzymes. At infinite Q content only the former mechanism is operative; at low Q content only the latter. (6) Duroquinone can be reduced directly by NADH dehydrogenase without mediation of ubiquinone, but duroquinol cannot be oxidized in the absence of ubiquinone. On the other hand, the reduction of cytochrome b by duroquinol does not require the presence of ubiquinone. (7) It is suggested that the need for ubiquinone for the oxidation of duroquinol is due to the requirement of ubisemiquinone for the oxidation of cytochrome b, duroquinol not being able to form a stabilized semiquinone.
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PMID:On the role of ubiquinone in the respiratory chain. 707 1

Treatment of rats with hydroxycobalamin[c-lactam] (HCCL), a cobalamin antagonist, results in both increased hepatic mitochondrial content and the development of defects in mitochondrial ubiquinol:cytochrome c oxidoreductase and cytochrome c oxidase. The present study was designed to evaluate changes in hepatic mitochondrial RNA contents in response to HCCL treatment in rats. After 2 weeks of HCCL treatment, hepatic contents of the mature mitochondrial mRNAs (expressed normalized to 28 S rRNA) encoding subunit II of cytochrome c oxidase (CO II), subunit 1 of NADH dehydrogenase (ND1), and cytochrome b were reduced to values 40-60% of those observed in RNA from control liver tissue. In addition, HCCL induced a pronounced accumulation of high molecular weight RNA species which hybridized to mitochondrial probes and represented polycistronic RNA sequences. The polycistronic RNAs were products of the heavy strand of the mitochondrial genome, and major species demonstrated hybridization patterns consistent with identifications corresponding to the 12-16 S rRNA, 12-16 S-ND1, 16 S-ND1, and CO II-ATP synthase subunit 6 regions of the mitochondrial genome. Maximal expression of the polycistronic mitochondrial RNA was observed after 2 weeks of HCCL treatment. Thus, HCCL treatment interferes with mitochondrial RNA processing and decreases the content of mature mitochondrial mRNAs. Altered expression of the mitochondrial genome may be responsible for the decreased electron transport chain activity known to result from HCCL administration.
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PMID:Hepatic cobalamin deficiency induced by hydroxycobalamin[c-lactam] treatment in rats is associated with decreased mitochondrial mRNA contents and accumulation of polycistronic mitochondrial RNAs. 750 36

A lambda cDNA library prepared from polyadenylated RNA isolated from Daudi cells was differentially screened to isolate cDNAs that recognize mRNA whose levels are reduced following interferon (IFN) treatment. Southern blot and DNA sequence analysis of 20 cDNA clones that were isolated revealed that they represented mitochondrially encoded mRNAs for the following proteins: cytochrome c oxidase subunits II and III, ATPase 6, cytochrome b, and subunit 1 of the NADH dehydrogenase. Northern blot analysis employing these cDNAs and oligonucleotides generated to the remaining mitochondrially encoded mRNAs demonstrated that IFN-alpha treatment of Daudi cells mediates a time-dependent suppression of the level of all of the mitochondrially encoded mRNAs. Study of this IFN-mediated effect reveals that: (i) the suppression of the level of these mRNAs is dependent on protein synthesis, (ii) it can be observed to occur prior to any detectable effect on thymidine incorporation, (iii) the degree of suppression correlates with the sensitivity of the cells to the anticellular action of IFN, and (iv) the suppression of the level of these RNAs appears to result from an effect on the level of transcription rather than on the stability of these mRNAs. A study of the level of cellular respiration in IFN-treated Daudi cells reveals a clear suppression 3 h following IFN treatment.
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PMID:Suppression of mitochondrial mRNA levels and mitochondrial function in cells responding to the anticellular action of interferon. 751 85

The flat revertant cell line R1, isolated from human activated Ha-ras oncogene transformed NIH/3T3 cells (EJ-NIH/3T3) by mutagen treatment, expresses a variant form of the actin-regulatory protein gelsolin, designated p92-5.7. To clone the gene encoding p92-5.7, gelsolin cDNAs were isolated from a cDNA library of R1 cells. In vitro transcription-translation and nucleotide sequence analyses of the cloned cDNAs identified a point mutation in codon 321 at the cause for the expression of p92-5.7. Considering gelsolin's function as an actin binding protein, the expression of alpha-actin, which is downregulated in many transformed fibroblasts, was analyzed. In EJ-NIH/3T3 cells no alpha-actin transcript was detected, whereas in R1 cells alpha-actin mRNA expression was restored to a level similar to NIH/3T3 cells. Immunofluorescence staining of the cells with an alpha-actin specific monoclonal antibody did not detect any alpha-actin containing microfilaments in EJ-NIH/3T3 cells, but revealed an ordered microfilament pattern in R1 and NIH/3T3 cells. In order to identify other genetic alterations that may also contribute to the revertant phenotype, genes with an elevated expression in R1 cells compared with the parental EJ-NIH/3T3 cells were isolated by using a differential hybridization approach. The identified sequences represented mitochondrial (cytochrome b, cytochrome c oxidase subunit II, NADH dehydrogenase subunits 1 and 4) and alpha 2 (type I) collagen genes. In summary, these results suggest that a complex alteration of the expression of cytoskeletal, mitochondrial and extracellular matrix components is closely associated with the flat reversion of R1 cells.
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PMID:[A study on alterations of gene expression in a flat revertant R1 from ras-oncogene transformed NIH/3T3 cells]. 769 63

We have sequenced a region (7,376-bp) of the mitochondrial (mt) DNA (54 kb) of the cellular slime mold, Dictyostelium discoideum. From the DNA and amino-acid sequence comparisons with known sequences, genes for ATPase subunit 9 (ATP9), cytochrome b (CYTB), NADH dehydrogenase subunits 1, 3 and 6 (ND1, ND3 and ND6), small subunit rRNA (SSU rRNA) and seven tRNAs (Arg, Asn, Cys, Lys, f-Met, Met and Pro) have been identified. The sequenced region of the mtDNA has a high average A + T-content (70.8%). The A + T-content of protein-genes (73.6%) is considerably higher than that of RNA genes (61.3%). Even with the strong AT-bias, the genetic code employed is most probably the universal one. All seven tRNAs are able to form typical clover leaf structures. The molecular phylogenetic trees of CYTB and SSU rRNA suggest that D. discoideum is closer to green plants than to animals and fungi.
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PMID:Codon usage, genetic code and phylogeny of Dictyostelium discoideum mitochondrial DNA as deduced from a 7.3-kb region. 773 10


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