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:1.6.5.3 (complex I)
8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The NADH-ubiquinone reductase preparation (Complex I) of bovine hart mitochondria catalysed in the presence of reduced coenzymes and ADP-Fe3+ the lipid peroxidation of liposomes prepared from mitochondrial lipids. The apparent Km values for the coenzymes and the optimal pH of the reactions agreed well with those of the lipid peroxidation of the submitochondrial particles treated with rotenone. On assay of the reduction of ADP-Fe3+ chelate by the reduction of cytochrome c in the presence of superoxide dismutase and antimycin A or by the oxidation of reduced coenzymes, the reactions were not affected by rotenone but were inhibited by thiol-group inhibitors. The properties of the ADP-Fe3+ reductase activity were highly consistent with those of the lipid-peroxidation reaction. These observations suggest that electrons from reduced coenzymes are transferred to ADP-Fe3+ chelate from a component between a mercurial-sensitive site and the rotenone-sensitive one of the NADH dehydrogenase and that the reduction of ADP-Fe3+ chelate by the NADH dehydrogenase is an essential step in the lipid peroxidation.
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PMID:Lipid peroxidation and the reduction of ADP-Fe3+ chelate by NADH-ubiquinone reductase preparation from bovine heart mitochondria. 678 84

Adriamycin (ADM) was found to have a two-step mode of action on the cardiac mitochondrial membrane. (1) An interaction with cardiolipin (CL) resulted in the formation of an ADM-CL complex able to transfer electrons from NADH to cytochrome c (cyt.c) as well as coenzyme Q (CoQ). This complex formation stimulates an increased activity of NADH-CoQ oxidoreductase (complex I) and CoQ-cyt.c oxidoreductase (complex III). (2) Transfer of electrons through ADM resulted in the formation of a very strong complex between ADM and CL. This new complex is different and much stronger than the already known ADM-CL complex.
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PMID:Mitochondrial membrane modifications induced by adriamycin-mediated electron transport. 683 34

Treatment of M. lysodeikticus protoplasts with subtilisin or pronase did not affect their permeability and led to a digestion of 20--30% of protein. DS-Na electrophoresis of protoplast membranes resulted in disappearance of three protein bands. This suggests that the outer surface of M. lysodeikticus protoplasts contains three proteins other than respiratory chain enzymes, which are subjected to an attack by proteinases. Treatment of the M. lysodeikticus membranes, isolated by osmotic shock, with proteinases resulted in a digestion of 20--50% of protein. The factors preventing the interaction between the membrane components (e.g. decrease of Mg2+ concentration, ultrasound, KCl, EDTA and particularly detergents) favoured the proteolysis; however, the bulk of the proteins remained insensitive to the effect of proteinases. The membranes pretreated with DS-Na or chlorophorm--methanol mixture proved to be good substrates for proteinases. Treatment of the membrane fraction with proteolytic enzymes allowed to obtain some data on localization of respiratory chain enzymes in the membrane stroma of M. lysodeikticus. Thus, cytochrome c is localized nearer to the membrane surface than cytochromes a and b, while malate dehydrogenase is plunged deeper into the membrane stroma as compared to NADH dehydrogenase.
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PMID:[Proteolysis as an approach to the study of protein distribution in the membrane of Micrococcus lysodeikticus]. 699 76

We investigated the changes of the inner-membrane components and the electron-transfer activities of bovine heart submitochondrial particles induced by the lipid peroxidation supported by NADPH in the presence of ADP-Fe3+. Most of the polyunsaturated fatty acids were lost as a result of the peroxidation, and phospholipids were changed to polar species. Ubiquinone was also modified to polar substances as the peroxidation proceeded. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis showed the disappearance of 27000-Mr and 30000-Mr proteins and the appearance of highly polymerized substances. Flavins and cytochromes were not diminished, but the respiratory activity was lost. The reactions of NADH oxidase and NADH-cytochrome c reductase were most sensitive to the peroxidation, followed by those of succinate oxidase and succinate-cytochrome c reductase. Succinate dehydrogenase and duroquinol-cytochrome c reductase were inactivated by more extensive peroxidation, but cytochrome c oxidase was only partially inactivated. NADH-ferricyanide reductase was not inactivated. The pattern of the inactivation indicated that the lipid peroxidation affected the electron transport intensively between NADH dehydrogenase and ubiquinone, and moderately at the succinate dehydrogenase step and between ubiquinone and cytochrome c.
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PMID:Alteration of inner-membrane components and damage to electron-transfer activities of bovine heart submitochondrial particles induced by NADPH-dependent lipid peroxidation. 708 19

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

Rat and pigeon heart mitochondria supplemented with antimycin produce 0.3-1.0nmol of H(2)O(2)/min per mg of protein. These rates are stimulated up to 13-fold by addition of protophores (carbonyl cyanide p-trifluoromethoxyphenylhydrazone, carbonyl cyanide m-chloromethoxyphenylhydrazone and pentachlorophenol). Ionophores, such as valinomycin and gramicidin, and Ca(2+) also markedly stimulated H(2)O(2) production by rat heart mitochondria. The enhancement of H(2)O(2) generation in antimycin-supplemented mitochondria and the increased O(2) uptake of the State 4-to-State 3 transition showed similar protophore, ionophore and Ca(2+) concentration dependencies. Thenoyltrifluoroacetone and N-bromosuccinimide, which inhibit succinate-ubiquinone reductase activity, also decreased mitochondrial H(2)O(2) production. Addition of cyanide to antimycin-supplemented beef heart submitochondrial particles inhibited the generation of O(2) (-), the precursor of mitochondrial H(2)O(2). This effect was parallel to the increase in cytochrome c reduction and it is interpreted as indicating the necessity of cytochrome c(1) (3+) to oxidize ubiquinol to ubisemiquinone, whose autoxidation yields O(2) (-). The effect of protophores, ionophores and Ca(2+) is analysed in relation to the propositions of a cyclic mechanism for the interaction of ubiquinone with succinate dehydrogenase and cytochromes b and c(1) [Wikstrom & Berden (1972) Biochim. Biophys. Acta283, 403-420; Mitchell (1976) J. Theor. Biol.62, 337-367]. A collapse in membrane potential, increasing the rate of ubisemiquinone formation and O(2) (-) production, is proposed as the molecular mechanism for the enhancement of H(2)O(2) formation rates observed on addition of protophores, ionophores and Ca(2+).
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PMID:Enhancement of hydrogen peroxide formation by protophores and ionophores in antimycin-supplemented mitochondria. 740 88

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

Three patients from a large consanguineous family, and one unrelated patient had exercise intolerance since early childhood and improved by supplementation with a high dosage of riboflavin. This was confirmed by higher endurance power in exercise testing. Riboflavin had been given because complex I, which contains riboflavin in FMN, one of its prosthetic groups, had a very low activity in muscle. Histochemistry showed an increase of subsarcolemmal mitochondria. The low complex I activity contrasted with an increase of the activities of succinate dehydrogenase, succinate-cytochrome c oxidoreductase and cytochrome c oxidase. Isolated mitochondria from these muscle specimens proved deficient in oxidizing pyruvate plus malate and other NAD(+)-linked substrates, but oxidized succinate and ascorbate at equal or higher levels than controls. Two years later a second biopsy was taken in one of the patients, and the activity of complex I had increased from 16% to 47% of the average activity in controls. In the four biopsies, cytochrome c oxidase activity correlated negatively with age. We suspect that this is due to reactive oxygen species generated by the proliferating mitochondria and peroxidizing unsaturated fatty acids of cardiolipin. Three of the four patients had low blood carnitine, and all were found to have hypocarnitinemic family members.
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PMID:Riboflavin-responsive complex I deficiency. 759 30

The ability of O2 metabolites derived from the xanthine-xanthine oxidase system to inhibit mitochondrial function was examined using freshly isolated rat liver mitochondria. Under 2,4-dinitrophenol-uncoupled conditions, mitochondria exposed to free radicals exhibited a significant decrease in O2 consumption supported by NAD(+)-linked substrates, but showed almost no change in O2 consumption in the presence of succinate and ascorbate. Oxidative stress caused the loss of intramitochondrial nicotinamide nucleotides, and addition of NAD+ fully prevented any fall in O2 consumption with NAD(+)-linked substrates. The activity of electron-transfer complex I (NADH oxidase and NADH-cytochrome c oxidoreductase) and the energy-dependent reduction of NAD+ by succinate were unaltered by oxidative stress. Exposure to free radicals also had an uncoupling effect at all three coupling sites. The degree of mitochondrial swelling was closely correlated with the inhibition of State-3 oxidation of site-I substrates and with the increase in State-4 oxidation of succinate. The immunosuppressive agent cyclosporin A completely prevented the mitochondrial damage induced by oxygen free radicals (swelling, Ca2+ release, sucrose trapping, uncoupling and selective inhibition of the mitochondrial respiration of site-I substrates). The same protective effect was found when Ca2+ cycling was prevented, either by chelating Ca2+ with EGTA or by inhibiting Ca2+ reuptake with Ruthenium Red. These findings suggest that the deleterious effect of free radicals on mitochondria in the present experimental system was triggered by the cyclosporin A-sensitive and Ca(2+)-dependent membrane transition, and not by direct impairment of the mitochondrial inner-membrane enzymes.
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PMID:Oxidative damage to mitochondria is mediated by the Ca(2+)-dependent inner-membrane permeability transition. 769 Oct 56

Electron transport and production of O2-/H2O2 by the NADH dehydrogenase flavin-semiquinone (FMNH.) and ubisemiquinone (UQH.) were studied in a model of in vivo ischemia-reperfusion in rat kidney. H2O2 production rates were assessed in isolated mitochondria using either succinate, with and without antimycin, or malate-glutamate, with and without rotenone. Respiratory activities of isolated mitochondria and activity of NADH- and succinate-cytochrome c reductase and of NADH- and succinate-dehydrogenase in submitochondrial particles were measured to evaluate the electron flux throughout respiratory carriers. The mitochondrial H2O2 production rate was approximately 1.5- and 4-times increased in ischemic and ischemic-reperfused kidneys, respectively. Ischemia caused a marked decrease in the electron transport throughout the NADH-UQ segment with no significant changes either in the NADH dehydrogenase activity or in the electron flux trough the succinate-cytochrome oxidase segment. Reperfusion did not further affect the NADH-ubiquinone segment but markedly inhibited the succinate-supported oxygen consumption, succinate-cytochrome c reductase and succinate dehydrogenase activity. Our results show a redistribution of the electron flux with an increased rate of superoxide anion/hydrogen peroxide production at NADH dehydrogenase in mitochondria subjected to ischemia only. After 10 min reperfusion an impairment of the electron flow at succinate-cytochrome c segment is established and hydrogen peroxide production by UQH. increases up to maximal values becoming the major source of superoxide anion/hydrogen peroxide.
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PMID:Mitochondrial sites of hydrogen peroxide production in reperfused rat kidney cortex. 772 10


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