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)

A specific requirement for coenzyme Q in the maintenance of trans-plasma-membrane redox activity is demonstrated. Extraction of coenzyme Q from membranes resulted in inhibition of NADH-ascorbate free radical reductase (trans electron transport), and addition of coenzyme Q10 restored the activity. NADH-cytochrome c oxidoreductase (cis electron transport) did not respond to the coenzyme Q status. Quinone analogs inhibited trans-plasma-membrane redox activity, and the inhibition was reversed by coenzyme Q. A 34-kDa coenzyme Q reductase (p34) has been purified from pig-liver plasma membranes. The isolated enzyme was sensitive to quinone-site inhibitors. p34 catalyzed the NADH-dependent reduction of coenzyme Q10 after reconstitution in phospholipid liposomes. When plasma membranes were supplemented with extra p34, NADH-ascorbate free radical reductase was activated but NADH-cytochrome c oxidoreductase was not. These results support the involvement of p34 as a source of electrons for the trans-plasma-membrane redox system oxidizing NADH and support coenzyme Q as an intermediate electron carrier between NADH and the external acceptor ascorbate free radical.
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PMID:Coenzyme Q reductase from liver plasma membrane: purification and role in trans-plasma-membrane electron transport. 776 18

Certain indocarbocyanine, thiacarbocyanine, and oxacarbocyanine dyes possessing short alkyl side-chains (one to five carbons) are potent inhibitors of mammalian mitochondrial NADH-ubiquinone reductase (EC 1.6.99.3) activity (Anderson et al., Biochem Pharmacol 41: 677-684, 1991; Anderson et al., Biochem Pharmacol 45: 691-696, 1993; Anderson et al., Biochem Pharmacol 45: 2115-2122, 1993), and act similarly to rotenone. This study examines the inhibitory capacities of twelve other carbocyanine dyes (six indocarbocyanines, four oxacarbocyanines, and two thiacarbocyanines) possessing long alkyl side-chains (seven to eighteen carbons with both saturated and unsaturated side-chains) on mitochondrial NADH, succinate and cytochrome c oxidase activities. Three of the indocarbocyanines inhibited electron transport chain activity, while three were non-inhibitory. Two of the oxacarbocyanines also inhibited electron transport chain activity, while the other two were without effect. Both the thiacarbocyanines were non-inhibitory. In contrast to previous studies, the long alkyl side-chain carbocyanines exhibited a broad spectrum of inhibition of respiratory chain activity, affecting either oxidation of all three substrates or of NADH and cytochrome c, rather than specific inhibition of mitochondrial NADH-ubiquinone reductase activity, indicating that there could be multiple binding sites for these compounds. The five inhibitory long side-chain carbocyanines also inhibited reduction of ferricyanide and coenzyme Q1 by NADH, using submitochondrial particles, but not when tested with purified complex I, indicating that the mitochondrial inner membrane was an integral component in their inhibitory capacity. No general correlation of side-chain length or degree of unsaturation and inhibitory capacity was discernible.
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PMID:Carbocyanine dyes with long alkyl side-chains: broad spectrum inhibitors of mitochondrial electron transport chain activity. 776 12

The enzymes of mitochondrial respiratory chain, NADH dehydrogenase (complex I) and cytochrome c oxidase (complex IV), were completely inhibited by 6-hydroxydopamine with IC50 = 10.5 microM and IC50 = 34 microM respectively. The enzyme inhibition was insensitive to the change of NADH or cytochrome c concentrations. The extent of complex I inhibition decreased as a consequence of both non-enzymatic and monoamine oxidase-catalyzed oxidation of 6-hydroxydopamine. Monoamine oxidase A and B inhibitors, tranylcypromine and clorgyline but not l-deprenyl increased the extent of 6-hydroxydopamine induced inhibition of complex I. Thus, 6-hydroxydopamine itself and not its oxidation products may be responsible for the neurotoxicity of this agent via inhibition of respiratory chain enzymes.
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PMID:Inhibition of mitochondrial complexes I and IV by 6-hydroxydopamine. 779 73

A mitochondrial DNA study of seven hydatidiform moles and seven full term placentas as controls was carried out to determine the role played by mitochondrial DNA as the only maternal genome participating in the pathogenesis of these trophoblastic growths. Mitochondrial DNA was digested by restriction enzymes Eco R1 and Hind III, processed by electrophoresis and stained by ethidium bromide. Molar mitochondrial DNA showed two restriction bands at 9416 and 2322 kbs with Eco R1 and one band at 2322 kbs with Hind III, whereas the controls showed three bands of 9416, 4361 and 2322 kbs with Eco 1, and two bands at 4361 and 2322 kbs with Hind III. The results were interpreted as a DNA alteration consistent with a mutation at level of tARN genes, initiating the reading of gen ND2 of Complex I, NADH dehydrogenase and affecting Complex CO III that transcribe cytochrome c and oxidoreductase genes. The alterations are considered as mutations probably resulted from folic acid deficiency at threshold levels during nuclear and mitochondrial DNA synthesis in oogenesis and meiosis that renders anucleated ova (cytoplasts), fertilized, and further accelerated development of a zygote bearing an entire androgenic genome.
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PMID:[Mitochondrial heredity in hydatidiform moles]. 795 51

The pathway of NADH oxidation in the procyclic Trypanosoma brucei brucei was investigated in a crude mitochondrial membrane fraction and in whole cells permeabilized with digitonin. NADH:cytochrome c reductase activity was 75% inhibited by concentrations of antimycin that inhibited 95% succinate:cytochrome c reductase activity suggesting that the major pathway for NADH oxidation in the mitochondria involved the cytochrome bc1 complex of the electron transfer chain. Both NADH:cytochrome c and NADH:ubiquinone reductase activities were inhibited 80-90% by rotenone indicating the presence of a complex I-like NADH dehydrogenase in the mitochondrion of trypanosomes. In whole cells permeabilized with low concentrations of digitonin, the oxidation of malate, proline and glucose (in the presence of salicylhydroxamic acid, the inhibitor of the alternate oxidase) was inhibited 30-50% by rotenone. The presence of an alternative pathway for NADH oxidation involving fumarate reductase was indicated by the observation that malonate, the specific inhibitor of succinate dehydrogenase, inhibited 30-35% the rate of oxygen uptake with malate and glucose as substrates in the digitonin-permeabilized cells. We conclude that in the mitochondrion of the procyclic form of T. brucei, NADH is preferentially oxidized by a rotenone-sensitive NADH:ubiquinone oxidoreductase; however, NADH can also be oxidized to some extent by the enzyme fumarate reductase present in the mitochondrion of T. brucei.
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PMID:Oxidation of NADH by a rotenone and antimycin-sensitive pathway in the mitochondrion of procyclic Trypanosoma brucei brucei. 807 26

NADH:ubiquinone reductase (EC 1.6.19.3), or complex I, was isolated from broad bean (Vicia faba L.) mitochondria. Osmotic shock and sequential treatment with 0.2% (v/v) Triton X-100 and 0.5% (w/v) [3-cholamidopropyl)dimethylammonio]-1-propanesulfate (CHAPS) removed all other NADH dehydrogenase activities. Complex I was solubilized in the presence of 4% Triton X-100 and then purified by sucrose-gradient centrifugation in the presence of the same detergent. The second purification step was hydroxylapatite chromatography. Substitution of CHAPS for Triton X-100 helped remove contaminants such as ATPase. The high molecular mass complex is composed of at least 26 subunits with molecular masses ranging from 6000 to 75,000 kD. The purified complex I reduced ferricyanide and ubiquinone analogs but not cytochrome c. NADPH could not substitute for NADH as an electron donor. The KM for NADH was 20 microM at the optimum pH of 8.0. The NH2-terminal sequence of several subunits was determined, revealing the ambiguous nature of the 42-kD subunit.
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PMID:Purification and preliminary characterization of mitochondrial complex I (NADH: ubiquinone reductase) from broad bean (Vicia faba L.). 810 9

A method for prediction of transmembrane segments from multiply aligned amino acid sequences is presented. For the calculations, two sets of propensity values were used: one for the middle, hydrophobic portion and one for the terminal regions of the transmembrane sequence spans. Average propensity values were calculated for each position along the alignment, with the contribution from each sequence weighted according to its dissimilarity relative to the other aligned sequences. Eight-residue segments were considered as potential cores of transmembrane segments and elongated if their middle propensity values were above a given threshold. End propensity values were also considered as stop signals. Only helices with length of 15 to 29 residues were allowed and corrections for strictly conserved charged residues were also made. The method is shown to be more successful than predictions based upon single sequences alone. In the test set of 28 families with 126 transmembrane segments, only five spans were not predicted or constituted false positives. The method is applied to sequence families for which data on transmembrane segments do not exist or are sparse or contradictory included voltage-gated potassium-channels, cytochrome c oxidases, NADH-ubiquinone oxidoreductase, beta-glucosides-specific phosphotransferase enzyme and major surface antigen of hepatitis B virus.
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PMID:Prediction of transmembrane segments in proteins utilising multiple sequence alignments. 812 32

The membranotropic properties of block co-polymers and their protein conjugates were studied by their effect on the rate of oxygen consumption by isolated liver mitochondria and on thymus-derived lymphocytes. The block co-polymers consisted of poly(ethylene oxide) (PoE) [poly(ethylene glycol)] and poly(propylene oxide) (PoP) to give either PoE-PoP or PoE-PoP-PoE. Both types inhibited uncoupled respiration of liver mitochondria in a medium containing glutamate and malate and also of lymphocytes. They also uncoupled respiration in the presence of succinate in K(+)-containing medium and of lymphocytes. A method is described for linking protein to the block polymers to form conjugates. Such conjugates were formed from alpha-chymotrypsin, BSA and cytochrome c, all of which produced similar effects on the respiration of the isolated mitochondria and lymphocytes. The data suggest that both the block co-polymers and their protein conjugates inhibit the NADH dehydrogenase complex and induce a K(+)-conductivity of the mitochondrial inner membrane; the surface activity of the conjugates allows them to pass through the plasma membrane and interact with the mitochondrial inner membrane.
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PMID:The influence of pluronics and their conjugates with proteins on the rate of oxygen consumption by liver mitochondria and thymus lymphocytes. 829 10

The 3-subunit iron-sulfur flavoprotein (NADH-artificial electron acceptor oxidoreductase) derived from complex I (EC 1.6.5.3) is rapidly and irreversibly inactivated in the presence of NADH. The rate of inactivation increases with a decrease of the enzyme concentration. The activities with ferricyanide, menadione and cytochrome c were lost synchronously during preincubation of the enzyme in the presence of NADH or dithionite under either aerobic or anaerobic conditions. The titration of the inactivation rate with the NADH/NAD+ pair suggests that reduction of a component with Em' = -325 mV (n = 2) is a prerequisite for a loss of the enzyme activity. Among the compounds tested only FMN and NAD+ were able to protect the enzyme against the reductive inactivation. NADH-induced loss of the enzyme activity in diluted solutions is accompanied with the synchronous appearance of a fluorescence characteristic for free FMN. It is concluded that the reduction of flavin leads to a strong decrease of FMN affinity to its specific binding site, and possible implications of the redox-dependent affinity changes in operation of NADH-ubiquinone reductase are discussed.
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PMID:Reductive inactivation of the mitochondrial three subunit NADH dehydrogenase. 839 15

A major limitation to a prolonged use of adriamycin (ADM) during a clinical treatment is its dose-dependent cardiotoxicity. This toxicity has been related to a general disturbance of the inner mitochondrial membrane structure and its essential biological functions, associated to the production of free radicals by the anthracyclines. 4'-Epiadriamycin (4'-epiADM), 4'-deoxyadriamycin (4'-deoxyADM), 4'-deoxy-4'-iodoadriamycin (4'-deoxy-4'-iodoADM) and 4'-demethoxydaunorubicin (4-demethoxyDNR) are ADM and daunorubicin (DNR) derivatives differing from their parent compounds by minor structural modifications. They are nevertheless documented as less cardiotoxic. Our purpose was to establish whether mitochondrial membrane damages induced in vivo in mice heart by those compounds are correlated with the free radical formation. Heart mitochondria of treated mice were isolated 48 h after a single drug injection in order to measure the acute mitochondrial toxicity. Enzymatic activities of complex I-III and complex IV of the mitochondrial respiratory chain, mitochondrial membrane fluidity and lipid peroxidation were measured. None of the ADM and DNR derivatives displayed a significant acute mitochondrial toxicity. A mitochondrial toxicity was however detected for 4-deoxyADM and 4-demethoxyDNR when drugs were given chronically, but it was strongly reduced as compared with ADM and DNR. Electron transfer between NADH and cytochrome c, formation of superoxide radicals and lipid peroxidation were measured in vitro for the various drugs. Comparison of the in-vivo and in-vitro results provides evidence that free radical production explains only partly the in-vivo toxicities.
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PMID:In-vivo and in-vitro mitochondrial membrane damages induced in mice by adriamycin and derivatives. 839 22


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