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:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antimycin-inhibited bovine heart submitochondrial particles generate O2- and H2O2 with succinate as electron donor. H2O2 generation involves the action of the mitochondrial superoxide dismutase, in accordance with the McCord & Fridovich [(1969) j. biol. Chem. 244, 6049-6055] reaction mechanism. Removal of ubiquinone by acetone treatment decreases the ability of mitochondrial preparations to generate O2- and H2O2, whereas supplementation of the depleted membranes with ubiquinone enhances the peroxide-generating activity in the reconstituted membranes. Addition of superoxide dismutase to ubiquinone-reconstituted membranes is essential in order to obtain maximal rates of H2O2 generation since the acetone treatment of the membranes apparently inactivates (or removes) the mitochondrial superoxide dismutase. Parallel measurements of H2O2 production, succinate dehydrogenase and succinate-cytochrome c reductase activities show that peroxide generation by ubiquinone-supplemented membranes is a monotonous function of the reducible ubiquinone content, whereas the other two measured activities reach saturation at relatively low concentrations of reducible quinone. Alkaline treatment of submitochondrial particles causes a significant decrease in succinate dehydrogenase activity and succinate-dependent H2O2 production, which contrasts with the increase of peroxide production by the same particles with NADH as electron donor. Solubilized succinate dehydrogenase generates H2O2 at a much lower rate than the parent submitochondrial particles. It is postulated that ubisemiquinone (and ubiquinol) are chiefly responsible for the succinate-dependent peroxide production by the mitochondrial inner membrane.
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PMID:Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. 18 49

Paraquat mediates a superoxide dismutase-inhibitable reduction of cytochrome c by suspensions of Escherichia coli B. Glucose was most effective in providing electrons for this cytochrome c reduction, but other nutrients could serve in this capacity, provided the cells were preconditioned by growth on these nutrients. Paraquat reduction depended upon a NADPH:paraquat diaphorase, present in the cytosol. Reduced paraquat could diffuse across the cell envelope and react with dioxygen, in the suspending medium, thus generating O2- in that compartment. Most of the paraquat reduced in the cell, under the conditions used, reoxidized in situ and most of the O2- production was thus intracellular. The partitioning of reduced paraquat between intracellular and extracellular compartments, prior to reaction with dioxygen, depended upon intracellular pO2 and any strategy which raised intracellular pO2 decreased the efflux of reduced paraquat and thus decreased extracellular O2- production. Extracellular O2- and H2O2 did contribute to cell damage in proportion to the amount produced. O2- appeared to be unable to cross the cell envelope in either direction and the only O2- which was effective in raising the rate of biosynthesis of the manganese-superoxide dismutase, was that generated within the cell.
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PMID:Paraquat and Escherichia coli. Mechanism of production of extracellular superoxide radical. 22 55

Purified rat liver NADPH-cytochrome c reductase supports iodination of tyrosine in a system including NADPH, cytochrome c and thyroid perioxidase. Catalase inhibits the iodination of tyrosine, while superoxide dismutase has no effect. Antibody developed in the rabbit against purified rat liver NADPH-cytochrome c reductase inhibits both reduction of cytochrome c and tyrosine iodination supported by the enzyme. The antibody forms a single precipitation line with thyroid extract, and inhibits NADPH cytochrome c reductase activity of the thyroid. The antibody partially inhibits iodination in a thyroid mitochondrial-microsomal fraction, but does not inhibit NADH-dependent iodination. The immunochemical studies indicate the participation of NADPH-cytochrome c reductase in thyroidal H2O generation, and the independent existence of NADPH-dependent and NADH-dependent H2O2 generation mechanisms in the thyroid.
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PMID:Participation of NADPH-cytochrome C reductase in thyroid hormone biosynthesis. 23 16

Thiourea and diethylthiourea, two compounds which react with hydroxyl radicals, inhibited NADPH-dependent microsomal oxidation of ethanol and 1-butanol. Inhibition by both compounds was more effective in the presence of the catalase inhibitor, azide. Inhibition by thiourea was noncompetitive with respect to ethanol in the absence of azide but was competitive in the presence of azide. Urea, a compound which does not react with hydroxyl radicals or H2O2, was without effect. Thiourea had no effect on NADH- and NADH-cytochrome c reductase, NADPH oxidase, and NADH- and NADPH-dependent oxygen uptake. Thiourea inhibited the activities of aniline hydroxylase and aminopyrine demethylase. Thiourea, but no other hydroxyl radical scavengers, e.g., dimethyl sulfoxide, mannitol, and benzoate, reacted directly with H202 and decreased H2O2 accumulation in the presence of azide. Therefore the actions of thiourea are complex because it can react with both hydroxyl radicals and H2O2. Differences between the actions of thiourea and those previously reported for dimethyl sulfoxide, mannitol, and benzoate, e.g., effects on drug metabolism, effectiveness of inhibition in the absence of azide, or kinetics of the inhibition, probably reflect the fact that thiourea reacts directly with H2O2 whereas the other agents do not. The current results remain consistent with the concept that microsomal oxidation of alcohols involves interactions of the alcohols with hydroxyl radicals generated from microsomal electron transfer.
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PMID:Effect of thiourea on microsomal oxidation of alcohols and associated microsomal functions. 42 8

The effect of inducing the rat liver nuclear mixed-function oxidase system by phenobarbital or 3-methylcholanthrene on NADPH- and NADH-dependent production of reactive oxygen intermediates was evaluated. The inducing agents produced a 2-fold increase in cytochrome P-450, a 50 to 70% increase in NADPH-cytochrome c reductase activity, and a 20 to 30% increase in NADH-cytochrome c reductase activity. Associated with these increases was a corresponding increase in NADPH- and NADH-dependent production of hydroxyl radical (.OH)-like species and of H2O2. Rates of .OH production were inhibited by catalase and partially sensitive to superoxide dismutase. The increase in nuclear production of .OH-like species after drug treatment appears to be due a corresponding increase in H2O2 generation. In contrast to H2O2 and .OH generation, production of thiobarbituric acid-reactive material by nuclei was not increased by the phenobarbital or 3-methylcholanthrene treatment. Redox cycling agents such as menadione and paraquat increased oxygen radical generation to similar extents in the control and the induced nuclei. These results indicate that induction of the nuclear mixed-function oxidase system by phenobarbital or 3-methylcholanthrene can result in a subsequent increase in production of reactive oxygen intermediates in the presence of either NADPH or NADH.
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PMID:Effect of phenobarbital and 3-methylcholanthrene treatment on NADPH- and NADH-dependent production of reactive oxygen intermediates by rat liver nuclei. 131 3

Previous results have shown that microsomes from ethanol-treated rats generate reactive oxygen intermediates at elevated rates as compared to pair-fed controls in the presence of NADH and especially NADPH. Since isolated rat liver nuclei can produce oxygen radicals with NADH or NADPH as reductants, the effect of chronic ethanol treatment on nuclear generation of reactive oxygen intermediates was determined. Ethanol treatment increased the activity of NADH (+27%) and NADPH (+50%) cytochrome c reductase in the nucleus. Nuclear lipid peroxidation, H2O2 production, and generation of hydroxyl radical-like species were increased by about 25 to 40% after ethanol treatment. In contrast to microsomes, where NADPH-dependent rates were higher than the NADH-dependent rates, in nuclei, NADH was as effective as, or even more reactive than NADPH in promoting production of various oxidizing species. The increases in oxygen radical production by nuclei after ethanol treatment were less than the increases found previously for microsomes. Moreover, rates of oxygen radical production by nuclei were less than 10% of the corresponding rates found with microsomes, suggesting that it is unlikely that the small increases found with nuclei after ethanol treatment contribute significantly towards the development of a state of oxidative stress in the liver.
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PMID:The effect of chronic ethanol consumption on NADH- and NADPH-dependent generation of reactive oxygen intermediates by isolated rat liver nuclei. 144 58

Trypanosoma cruzi epimastigotes permeabilized with digitonin (65 micrograms (mg protein)-1) to measure mitochondrial respiration were exposed to different substrates. Although none of the NADH-dependent substrates stimulated respiration, succinate supported not only oxygen consumption but also oxidative phosphorylation (respiratory control ratio of 1.9 +/- 0.3) indicating that the mitochondria were coupled. The rate of NADH-dependent oxygen consumption by membrane fractions (9.4 +/- 0.7 nmol min-1 (mg protein)-1) was reduced by 50% upon addition of catalase indicating that the electrons from NADH oxidation reduced oxygen to H2O2. NADH-dependent H2O2 production (16 +/- 1 nmol min-1 (mg protein)-1) was confirmed using cytochrome c peroxidase. This activity was inhibited by fumarate by 70%, suggesting a competition between fumarate and oxygen for the electrons from NADH, probably at the fumarate reductase level. The respiratory chain inhibitor antimycin blocked both respiration by intact cells and succinate-dependent cytochrome c by isolated membranes. No inhibition by antimycin was observed when NADH replaced succinate as an electron donor, indicating that the electrons from NADH oxidation reduced cytochrome c through a different route. Malonate blocked not only succinate-cytochrome c reductase and fumarate reductase, but also intact cell motility. These results suggest that succinate has a central role in the intermediate metabolism of i. cruzi, as it may be used for respiration or excreted to the extracellular space under anaerobic conditions. In addition, 2 potential sources of H2O2 were tentatively identified as: (a) the enzyme fumarate reductase; and (b) a succinate-dependent site, which may be the semiquinone form of Coenzyme Q9, as in mammalian mitochondria.
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PMID:Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes. 151 31

A NADH oxidase has been purified from the extreme thermophile Thermus thermophilus HB8 by several chromatographic steps. The purified enzyme was essentially homogeneous as judged by gel electrophoresis under denaturing conditions and by determination of the N-terminal amino acids sequence. It is a monomeric flavin-adenine-dinucleotide-containing flavoprotein with an apparent molecular mass of 25 kDa and an 1:1 ratio of FAD to the polypeptide chain. The purified enzyme catalyzes the oxidation of reduced NADH or NADPH with the formation of H2O2. The apparent Km values for NADH and NADPH are 4.14 microM and 14.0 microM (pH 7.2 at room temperature), respectively, with a sixfold greater kcat/Km values for NADH compared to NADPH. The enzyme uses O2 as an electron acceptor in the presence of either FAD, riboflavin 5'-phosphate or riboflavin as cofactor. In addition, the enzyme is able to catalyze electron transfer from NADH to various other electron acceptors (methylene blue, cytochrome c, p-nitroblue tetrazolium, 2,6-dichloroindophenol and potassium ferricyanide), even in the absence of flavin shuttles. No significant inhibition of the NADH oxidoreductase activity by superoxide dismutase was observed with these artificial electron acceptors, indicating that electron transfer occurs mainly from NADH directly to the electron acceptors, not via O2- as an intermediate. The purified NADH oxidase exhibits highest activity at pH 5.0 and is stable at elevated temperatures of up to 80 degrees C.
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PMID:Purification and characterization of a NADH oxidase from the thermophile Thermus thermophilus HB8. 157 5

A high-abundance NADH-oxidizing enzyme (NADH: acceptor oxidoreductase, EC 1.6.99.3) has been identified and isolated from a range of anaerobic extreme thermophiles, including strains of Clostridium thermohydrosulfuricum and Thermoanaerobium brockii. By use of a pseudo-affinity salt-promoted adsorbent, a nearly pure sample was obtained in one step; remaining impurities were separated by ion-exchange. The fully active purified enzyme contains FAD (two molecules per subunit of 75-78 kDa) and iron-sulphur, and is hexameric in its most active form. The reaction with oxygen is a one- or two-electron transfer to produce superoxide radical and H2O2; other acceptors include tetrazolium salts, dichlorophenol-indophenol, menadione and ferricyanide. The role of the enzyme is not clear; it was found not to be NAD:ferredoxin oxidoreductase, which is a major NADH-utilizing enzyme in these organisms.
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PMID:A thermostable NADH oxidase from anaerobic extreme thermophiles. 159 37

Mercuric ion (Hg(II)) causes oxidative tissue damage in kidney cortical cells. We studied the in vitro effects of Hg(II) on hydrogen peroxide (H2O2) production by rat kidney mitochondria, a principal intracellular target of Hg(II). In mitochondria supplemented with a respiratory chain substrate (succinate or malate/glutamate) and an electron transport inhibitor (antimycin A (AA) or rotenone), Hg(II) (30 nmol/mg protein) increased H2O2 formation approximately 4-fold at the ubiquinone-cytochrome b region (AA-inhibited) and 2-fold at the NADH dehydrogenase region (rotenone-inhibited). Concomitantly, Hg(II) increased iron-dependent lipid peroxidation 3.5-fold at the NADH dehydrogenase region, but only by 25% at the ubiquinone-cytochrome b region. The mitochondrial concentration of reduced glutathione (GSH) decreased both with incubation time and Hg(II) concentration. Hg(II), at a concentration of 12 nmol/mg protein, caused almost complete depletion of measurable GSH in substrate-supplemented mitochondria after a 30-min incubation. In electron transport-inhibited mitochondria, Hg(II) caused greater depletion of GSH in rotenone-inhibited than in AA-inhibited mitochondria, consistent with the effects of Hg(II) on lipid peroxidation. These results suggest that Hg(II) at low concentrations depletes mitochondrial GSH and enhances H2O2 formation in kidney mitochondria under conditions of impaired respiratory chain electron transport. The increased H2O2 formation by Hg(II) may lead to oxidative tissue damage, such as lipid peroxidation, observed in mercury-induced nephrotoxicity.
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PMID:Mercury-induced H2O2 production and lipid peroxidation in vitro in rat kidney mitochondria. 176 76


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