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:1.6.5.2 (NQO1)
6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anthraquinone-based antitumour agents mitoxantrone, daunorubicin and ametantrone were found to be substrates for NAD(P)H (quinone acceptor) oxidoreductase (DT-diaphorase) [QAO] isolated from rat liver. This was indicated by the stimulation of QAO-dependent NADPH oxidation by these agents. This effect followed Michaelis-Menten kinetics and was dependent on the concentration of QAO, inhibited by the specific QAO inhibitor dicumarol (15 microM) and enhanced by the QAO activators bovine serum albumin (0.01%) and Triton X-100 (0.03%). As indicated by the Vmax/Km ratio, mitoxantrone (26.53) was considerably more active than ametantrone (11.25) or daunorubicin (7.35). Metabolism of these anthraquinones was associated with the formation of superoxide anions, hydrogen peroxide and hydroxyl radicals as indicated by electron spin resonance spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide. This is likely to be due to the slow auto-oxidation of the respective dihydroquinones in the presence of molecular oxygen. QAO needs to be considered as a possible route of bioreductive activation of these agents.
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PMID:NAD(P)H (quinone acceptor) oxidoreductase (DT-diaphorase)-mediated two-electron reduction of anthraquinone-based antitumour agents and generation of hydroxyl radicals. 131 84

Ubiquinone (UQ) reductase activity which reduces UQ to ubiquinol (UQH2) in rat tissues was roughly proportional to the UQH2/total UQ ratio in respective tissues. The highest activity was found in the liver, showing the highest UQH2/total UQ ratio. A greater part of liver UQ reductase activity was located in the cytosol. Within a week, the liver UQ reductase activity decreased by 80% even at -20 degrees C. The DT-diaphorase activity was stable. UQ reductase required NADPH as the hydrogen donor and was not inhibited by a less than 1 microM concentration of dicoumarol. There was no stimulation of UQ reductase in the presence of bovine serum albumin nor in Triton X-100. Yet, both stimulated DT-diaphorase. As a result, UQ reductase appeared to be a novel NADPH-UQ oxidoreductase and responsible for the UQ redox state in liver.
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PMID:A novel ubiquinone reductase activity in rat cytosol. 146 65

The myenteric plexus of the domestic fowl (Gallus domesticus) small intestine was studied by means of silver staining, glyoxylic acid-induced fluorescence, the modified Koelle-Friedenwald method for the detection of acetylcholinesterase, NADH-diaphorase techniques and the unlabelled antibody method involving the use of an antiserum raised against GABA conjugated by glutaraldehyde to bovine serum albumin. The majority of the perikarya were in the ganglia, with an average density of 3370 +/- 942 nerve cells/cm2. Cholinesterase-positive and a few GABA-immunoreactive nerve cell bodies were seen in the myenteric ganglia, while fluorescent ganglion cells were not observed. In addition to AChE and GABA-positive nerve fibres, a rich fluorescent network of varicose and nonvaricose nerve fibres was detected, pointing to the presence of an extrinsic aminergic system in the domestic fowl myenteric plexus. Electron microscopic observations on nerve cells, axon profiles and varicosites with various vesicle populations were in good agreement with the histochemical findings.
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PMID:Histochemical characterization of myenteric plexus in domestic fowl small intestine. 207 64

DT-diaphorase [NAD(P)H dehydrogenase (quinone), EC 1.6.99.2] is a flavoprotein enzyme widely distributed in the cytosolic fractions of various animal tissues. It is also called menadione reductase or NAD(P)H-quinone reductase and catalyzes NAD(P)H-dependent 1-, 2- or 4-electron reduction of certain redox dyes, aromatic nitro compounds, aromatic C-nitroso compounds and probably azo-dyes, as well as menadione (vitamin K3) and other quinones. Dicumarol exerts characteristic inhibition on DT-diaphorase, whereas serum albumin and certain non-ionic detergents exert activation. Excessive concentrations of many of the electron acceptors inhibit the activity of this enzyme. The physiological significance of DT-diaphorase is still obscure because the physiological vitamins (K1 and K2) and coenzyme Q10 are difficult to reduce with this enzyme. Results of recent studies suggest that DT-diaphorase prevents formation of active oxygen species. Activities in liver and other tissues are known to be enhanced by administration of chemicals including certain carcinogens such as 3-methylcholanthrene (3-MC), anti-oxidants such as 3-tert-butyl-4-hydroxyanisole (BHA), and other compounds. Both basal and induced activities vary considerably with tissue, sex, strain and species of animals. The strain variations in activities in rat and mouse liver are known to be inherited, and the trait of hereditary transmission can be adequately explained by postulating two loci of genes or gene clusters regulating the activity. Resistance of animals to various toxic or carcinogenic substances may be promoted by BHA administration and depressed by dicumarol administration. Thus, attention has been focused on the role played by DT-diaphorase in the detoxication of foreign compounds. Knowledge on strain variations in basal and induced activities of tissue DT-diaphorase is of potential value when choosing a rat or mouse strain suitable for studying the toxic effects of drugs, especially drugs expected to be detoxified by reductive metabolism. With future progress in research on DT-diaphorase, this enzyme might be applied to prophylactic and therapeutic medicine.
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PMID:Advances in research on DT-diaphorase--catalytic properties, regulation of activity and significance in the detoxication of foreign compounds. 212 71

A fluorometric flow-injection method for determining carnitine with use of immobilized enzymes carnitine dehydrogenase (EC 1.1.1.108) and diaphorase (EC 1.8.1.4) was developed and applied to the assay of carnitine in serum of patients treated with valproic acid. After fractionation and hydrolysis of carnitines in serum samples by perchloric acid and potassium hydroxide, liberated carnitine was converted to resorufin by immobilized carnitine dehydrogenase and diaphorase in the presence of beta-NAD+ (1.0 mmol/L), resazurin (12.5 mumol/L), and Tris acetate (0.6 mol/L, pH 9.0) at 37 degrees C. The fluorescence intensity of resorufin was monitored at lambda Ex 560 nm and lambda Em 580 nm. The calibration curve was linear for carnitine amounts from 0.1 to 1.0 nmol. Quantitative analytical recovery and satisfactory within- and between-run imprecision of carnitine in each carnitine fraction were obtained. Interference by bilirubin, serum albumin, and hemoglobin was negligible. Carnitine deficiencies were detected in about 20% of the valproic acid-treated patients (n = 198). The present method should be useful for monitoring carnitine deficiencies in clinical laboratories.
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PMID:Fluorometric determination of carnitine in serum with immobilized carnitine dehydrogenase and diaphorase. 225 48

Bernofsky, Carl (The University of Kansas, Kansas City), and Russell C. Mills. Diaphorases from Aerobacter aerogenes. J. Bacteriol. 92:1404-1414. 1966.-Five enzymes which catalyze the reduction of 2,6-dichlorophenol-indophenol by reduced nicotinamide adenine dinucleotide (NADH(2)) have been separated from sonic extracts of Aerobacter aerogenes B199 by diethylaminoethyl (DEAE) cellulose chromatography. Three major chromatographic fractions (enzymes I, II, and III) account for most of the activity in the extract. Of the two minor fractions, one is associated with cytochrome b(1). The other is extremely labile, and was not studied further. The chromatographed diaphorases appear to have a specific requirement for flavin mononucleotide. They are also readily inactivated by dilution; however, this can be prevented by a combination of phosphate buffer, bovine serum albumin, and flavin mononucleotide. The different enzymes are clearly distinguishable by their activities with NADH(2) and reduced nicotinamide adenine dinucleotide phosphate (NADPH(2)) in the presence of various electron acceptors (2,6-dichlorophenol-indophenol, ferricyanide, menadione, and cytochrome c), and by their responses to inhibitors (amobarbital, antimycin A, Atabrine, p-chloromercuribenzenesulfonate, dicumarol, and 2,4-dinitrophenol). With 2,6-dichlorophenol-indophenol as acceptor, enzymes I, II, and III have comparable activities with either NADH(2) or NADPH(2). With menadione and ferricyanide as acceptors, enzymes II and III exhibit very high, NADH(2)-specific activities. When cytochrome c is the acceptor, however, enzyme III shows greater activity with NADPH(2) as the electron donor. Ferricyanide is the most active acceptor for the cytochrome b(1)-containing fraction. Coenzyme Q(6) does not appear to serve as an acceptor. All the diaphorases, with the exception of that in the cytochrome b(1)-containing fraction, are inhibited by p-chloromercuribenzenesulfonate. Amobarbital is relatively ineffective and inhibits only the indophenol reductase activity of enzyme I. The menadione reductase activity of enzymes I, and II, and the diaphorases in the cytochrome b(1)-containing fraction are strongly inhibited by antimycin A, 2,4-dinitrophenol, dicumarol, and Atabrine. However, the menadione reductase activity of enzyme III is affected only by the last three of these inhibitors. The diaphorases in sonic-treated extracts do not appear to be associated with a particulate fraction.
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PMID:Diaphorases from Aerobacter aerogenes. 592 71

NAD(P)H-dependent C-nitrosoreductase of porcine heart cytosol was purified 12,000-fold in the presence of NADH with an overall yield of 2.2%. The purification procedure included ammonium sulfate fractionation, gel filtration with Sephadex G-100, ion-exchange chromatography on DEAE-Sephadex A-50, hydrophobic chromatography on Octyl-Sepharose CL-4B, and gel filtration with Sephadex G-200. The purity of the preparation was approximately 90% and the molecular weight of the enzyme estimated by gel filtration was about 60,000. The purified enzyme was composed of two molecular forms, nitrosoreductases 1 and 2, having isoelectric points of 8.45 and 8.6, respectively. A significant amount of zinc was found in the preparation by X-ray fluorescence analysis. The enzyme as it was prepared was colorless, but, after oxidation with p-nitrosophenol followed by gel filtration in the absence of NADH, it showed the absorption spectrum of a flavoprotein. Spectral data indicated the presence of 1 mol of flavin per mol of the enzyme. The molecular turnover number was calculated to be 10,000 nmol p-nitrosophenol reduced to p-aminophenol per min per nmol enzyme at pH 5.8 and 22 degrees C. The activity was inhibited by p-chloromercuribenzoate by 50% at a concentration of 3 x 10(-5) M. Besides the nitrosoreductase activity, the purified preparation showed NAD(P)H-dependent menadione reductase activity. The activities were both strongly inhibited by dicumarol and markedly activated by serum albumin and by Tween 20. These results indicate the probable identity of this enzyme with soluble NAD(P)H dehydrogenase (quinone) [EC 1.6.99.2].
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PMID:Studies on the enzymatic reduction of C-nitroso compounds. V. Molecular properties of porcine heart C-nitrosoreductase and identity of this enzyme with NAD(P)H dehydrogenase. 675 11

Copper Fenton systems (Cu(II)/H2O2 and Cu(II)/Asc) inactivated the lipoamide reductase and enhanced the diaphorase activity of pig-heart lipoamide dehydrogenase (LADH). Cupric ions alone were less effective. As a result of Cu(II)/H2O2 treatment, the number of titrated thiols in LADH decreased from 6 to 1 per subunit. NADH and ADP (not NAD+ or ATP) enhanced LADH inactivation by Cu(II). NADH also enhanced the effect of Cu(II)/H2O2. Dihydrolipoamide, dihydrolipoic acid, Captopril, acetylcysteine, EDTA, DETAPAC, histidine, bathocuproine, GSSG and trypanothione prevented LADH inactivation. 100 microM GSH, DL-dithiothreitol, N-(2-mercaptopropionylglicine) and penicillamine protected LADH against Cu(II)/Asc and Cu(II), whereas 1.0 mm GSH and DL-dithiothreitol also protected LADH against Cu(II)/H2O2. Allopurinol provided partial protection against Cu(II)/H2O2. Ethanol, mannitol, Na benzoate and superoxide dismutase failed to prevent LADH inactivation by Cu(II)/H2O2 or Cu(II). Catalase (native or denaturated) and bovine serum albumin protected LADH but that protection should be due to Cu binding. LADH inhibited deoxyribose oxidation and benzoate hydroxylation by Cu(II)/H2O2. It is concluded that site-specifically generated HO, radicals were responsible for LADH inactivation by Cu(II) Fenton systems. The latter effect is discussed in the context of ischemia-reoxygenation myocardial injury.
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PMID:Inactivation of heart dihydrolipoamide dehydrogenase by copper Fenton systems. Effect of thiol compounds and metal chelators. 775

Trypanosoma brucei S427cl1 organisms made 6 divisions in modified minimal essential medium (BMEM) supplemented with fetal bovine serum (FBS)-low or high density lipoprotein (LDL, HDL) and fatty acid-free bovine serum albumin (FAF-BSA). Omission of lipoproteins or FAF-BSA from the medium caused the parasites to accumulate in G1 of the cell cycle and to lose the ability to replicate at 37 degrees C. Proteinase K-treated LDL or HDL, which did not have detectable apolipoprotein, supported the G1 to S cell cycle transition of T. brucei S427cl1 organisms in BMEM supplemented with FAF-BSA. Addition of C6:0, C7:0 or fatty C8:0 fatty acid (1 mol fatty acid mol-1 FAF-BSA in the incubation mixture) to serum-free medium supplemented with LDL or HDL and FAF-BSA prevented T. brucei S427cl1 organisms from progressing through G1 into S of the cell cycle. T. brucei S427cl1 organisms became stumpy-like forms during plateau phase growth under axenic conditions. Stumpy-like T. brucei S427cl1 organisms were mainly in G1 of the cell cycle, expressed raised levels of NAD diaphorase activity, were unable to replicate at 37 degrees C, but were able to differentiate to replicating procyclic organisms. Medium collected from plateau phase cultures of T. brucei S427cl1 did not support the G1 to S cell cycle transition of exponentially growing T. brucei organisms. The capacity of plateau phase medium to support G1 to S transition of T. brucei S427cl1 organisms was restored by addition of FAF-BSA and its capacity to support 4 cycles of replication of the parasites was restored by addition of FAF-BSA and LDL or HDL.
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PMID:Control of G1 to S cell cycle progression of Trypanosoma brucei S427cl1 organisms under axenic conditions. 843 15

Nitrate reductase from the yeast Candida nitratophila was found to contain one molecule of cytochrome b557 and one atom of molybdenum per subunit. FAD/haem-dependent diaphorase activity (haem domain) was associated with a 40 kDa tryptic fragment of the subunit. The 50 amino-terminal residues of this fragment were determined, and the sequence did not show significant similarity to deduced sequences of other nitrate reductases previously published. Increasing ionic strength in vitro had a stimulatory effect on enzymic activity via stimulation of the molybdenum-dependent terminal nitrate-reducing activity. Stimulation of activity by exogenous protein (bovine serum albumin or casein) also appeared to be an ionic effect. Stimulation of catalytic activity by phosphate was a separate effect.
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PMID:Further characterization of the assimilatory nitrate reductase from the yeast Candida nitratophila. 847 56


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