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)

Cytochrome-deficient cells of a strain of Escherichia coli lacking 5-amino-levulinate synthetase have been used to study proton translocation associated with the reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase region of the electron transport chain. Menadione was used as electron acceptor, and mannitol was used as the substrate for the generation of intracellular NADH. The effects of iron deficiency on NADH- and D-lactate-menadione reductase activities were studied in iron-deficient cells of a mutant strain unable to synthesize the iron chelator enterochelin; both activities were reduced. The NADH- menadione reductase activity in cytochrome-deficient cells was associated with proton translocation and could be coupled to the uptake of proline. However proton translocation associated with the NADH-menadione reductase activity was prevented by a mutation in an unc gene. It was concluded that there is no proton translocation associated with the NADH-dehydrogenase region of the electron transport chain in E. coli and that the proton translocation obtained with mannitol as substrate is due to the activity of membrane-bound adenosine triphosphatase.
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PMID:Proton translocation in cytochrome-deficient mutants of Escherichia coli. 15 8

The transverse distribution of enzyme proteins and phospholipids within microsomal membranes was studied by analyzing membrane composition after treatment with proteases and phospholipases. Upon trypsin treatment of closed microsomal vesicles, NADH- and NADPH-cytochrome c reductases as well as cytochrome b5 were solubilized or inactivated, while cytochrome P-450 was partially inactivated. When microsomes were exposed to a concentration of deoxycholate which makes them permeable to macromolecules but does not disrupt the membrane, the detergent alone was sufficient to release four enzymes: nucleoside diphosphatase, esterase, beta-glucuronidase, and a portion of the DT-diaphorase. Introduction of trypsin into the vesicle lumen inactivated glucose-6-phosphatase completely and cytochrome P-450 partially. The rest of this cytochrome, ATPase, AMPase, UDP-glucuronyltransferase, and the remaining 50% of DT-diaphorase activity were not affected by proteolysis from either side of the membrane. Phospholipase A treatment of intact microsomes in the presence of albumin hydrolyzed all of the phosphatidylethanolamine, phosphatidylserine, and 55% of the phosphatidylcholine. From this observation, it was concluded that these lipids are localized in the outer half of the bilayer of the microsomal membrane; Phosphatidylinositol, 45% of the phosphatidylcholine, and sphingomyelin are tentatively assigned to the inner half of this bilayer. It appears that the various enzyme proteins and phospholipids of the microsomal membrane display an asymmetric distribution in the transverse plane.
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PMID:Enzyme and phospholipid asymmetry in liver microsomal membranes. 19 Feb 41

One hour after a single i.v. dose of 250 mg/kg folic acid, the straight portion of distal tubules in the outer medulla of rat kidneys showed a distinct reduction in succinate dehydrogenase, NADH2-diaphorase, glutamate dehydrogenase, cytochrome oxydase, Na+/K+-ATPase, and acid phosphatase activity. In contrast, the proximal tubules exhibited only a reduction in glutamate dehydrogenase and alkaline phosphatase activity. At this time the straight portion of the distal tubules, whose enzyme activity had changed, showed partly regressive epithelial changes. 24 hours after folic acid administration an even greater reduction in enzyme activity had occurred in the straight portion of distal tubules; these structures also became dilated. The adjacent collecting tubules and the corresponding proximal tubules were also severely dilated, the proximal tubules showing a loss in enzyme acitivities similar to those observed in the distal tubules. 48 hours after folic acid administration the changes largely resembled those observed after 24 hours, but were more pronounced. At this time a tubular regeneration was observed. 72 hours after folic administration extensive normalization of the histological and histochemical changes had occured. It is postulated that a disturbance of the hairpin counter-current mechanism occurs as a result of a direct, concentration-dependent effect of folic acid on the enzymes of the energy supplying metabolism. A dilation in the region of the loop of Henle and the collecting tubules occurs subsequently.
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PMID:Enzyme histochemistry of rat folic acid nephropathy. 19 86

The rabbits being repeatedly poisoned with small doses of sodium cyanide, the activity of succinic dehydrogenase in the tissues does not essentially change. The activity of NAD.H2-cytochrome-c-reductase and NAD.H2-diaphorase in the brain, myocardium and kidneys increases. Under histotoxic hypoxia the level of iron in the tissues increases by 52-93%, that of copper--by 28-36%, of zinc--by 21-74% and of cobalt by 28-40%. There existed a positive correlation between the content of iron and the activity of NAD-dependent enzymes. In nonlethal form of histotoxic hypoxia the content of nonhemin iron and the activity of NAD.H2-cytochrome-c-reductase in the mitochondria of the brain increases by 25% and 17%, respectively, and a direct correlation is revealed between them.
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PMID:[Iron, copper, zinc and cobalt content and activity of respiratory metalloenzymes in animal tissues under toxic hypoxia]. 68 69

Effect of Di(2-ethylhexyl) phthalate (DEHP), was investigated on chemical constituents and activity of certain enzymes of rat liver. A significant increase in liver weight; total and relative to body weight; decrease in total, free and esterified cholesterol; and no change in dry weight, moisture; RNA, DNA, total lipids, phospholipids, pyruvic acid and lactic acid contents was observed in liver of DEHP-treated rats as compared to controls. Activity of 3 mitochondrial enzymes, malic dehydrogenase, cytochrome-c-oxidase and diaphorase were significantly decreased while that of NADH-cytochrome c reductase, RNAase and DNAase remained unaltered upon treatment. The results suggest that DEHP exerts its hepatotoxic effects by interfering with bioenergetics of the cell.
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PMID:Effect of Di-(2-ethylhexyl) phthalate (DEHP) on chemical constituents and enzymatic activity of rat liver. 73 83

Male F344/NCr rats were exposed to low dietary concentrations of Aroclor 1254 (0-33 ppm) for 7 days, following which the induction of selected hepatic drug metabolizing enzymes was monitored. CYP1A1, measured indirectly by assaying the O-dealkylation of ethoxyresorufin in 9000 g supernatants, was increased 1.5-, 3-, 8-, and 37-fold following 7 days of exposure to 1.0, 3.3, 10, and 33 ppm Aroclor, respectively. In contrast, the O-dealkylation of benzyloxyresorufin, an indirect measure of CYP2B1 activity, was increased approximately 4-fold following exposure to 33 ppm dietary Aroclor. Measurement of the non-P450-mediated activities epoxide hydrolase, DT-diaphorase, and aldehyde dehydrogenase (NADP+, benzaldehyde) revealed < 4-fold inductions following feeding of 33 ppm Aroclor. In view of the relatively high sensitivity of the CYP1A-specific catalytic endpoint as a biomarker for Aroclor exposure, alternative endpoints for detecting induction of this subfamily of P450 were also examined. The extent of in vivo CYP1A induction was assessed by measuring serum concentrations of zoxazolamine 150 min following an intraperitoneal dose of 100 mg/kg body wt. Slight decreases in serum zoxazolamine concentration were observed in rats exposed to as little as 1.0 ppm dietary Aroclor 1254, while profound decreases were seen in rats exposed to > or = to 10 ppm Aroclor. Immunodetection of CYP1A1 protein, with a monoclonal antibody directed against this cytochrome, revealed a 2.9-fold increase in rats exposed to as little as 1.0 ppm Aroclor, and approximately 10- and 44-fold increases following exposure to 3.3 and 10 ppm dietary Aroclor, respectively. Increases in total hepatocellular RNA coding for CYP1A1 and CYP1A2, quantified by hybridization to specific oligonucleotide probes, corresponded well to the increases in hepatic O-dealkylase activity for ethoxyresorufin (CYP1A1) and methoxyresorufin (CYP1A2), respectively. Thus, CYP1A induction, directly or indirectly measured with a variety of endpoints, represents a highly sensitive biomarker for exposure to relatively low doses of Aroclor 1254 in the rat.
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PMID:Induction of hepatic CYP1A in male F344/NCr rats by dietary exposure to Aroclor 1254: examination of immunochemical, RNA, catalytic, and pharmacokinetic endpoints. 128 48

Male C57Bl/6 mice were treated for 5 days with 0.05% perfluorooctanoic acid (PFOA) in their diet. This treatment resulted in a potent induction of peroxisomal fatty acid beta-oxidation in the liver. In order to investigate recovery from treatment with PFOA, mice were given normal laboratory chow for up to 20 days after termination of PFOA administration. It was established that the activities of peroxisomal lauoryl-CoA oxidase and palmitoyl-CoA oxidation were still elevated 2-3 weeks after termination of treatment. The catalase activity recovered in the cytosolic fraction was also still significantly elevated after 20 days with normal laboratory chow. Furthermore, the protein content of the mitochondrial fraction was increased by PFOA and had not returned to control level at the end of the recovery period. Perfluorooctanoic acid also caused a persistent effect in omega hydroxylation of lauric acid (cytochrome P-452). The activities of cytosolic DT-diaphorase and glutathione transferase were also enhanced by PFOA. However, these two enzymes recovered relatively rapidly from the treatment (2-20 days). This study reveals two different patterns of recovery from PFOA treatment, one involving parameters that recovered completely, or almost completely, from PFOA treatment after 20 days and another involving parameters that were still elevated at the end of the recovery period.
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PMID:Perfluorooctanoic acid has persistent effects on peroxisome proliferation and related parameters in mouse liver. 129 9

The cytochrome b subunit of the bc1 complexes contains two cytochrome components (bL and bH) and is the locus of both a quinol-oxidizing site (Qo or Qz) and a quinone-reducing site (Qi or Qc). Sequence alignments of this subunit from over 20 eukaryotic and prokaryotic species have revealed a remarkable degree of conservation, including approximately 20 totally conserved residues. In this paper, site-directed mutagenesis has been used to examine the structural or functional roles of 5 of these highly conserved residues, Gly48, Gln58, Ser102, Phe104, and Pro202, all predicted to be within transmembrane alpha-helical segments. The mutants were made in the bc1 complex of Rhodobacter sphaeroides, a photosynthetic bacterium. The ability to use spectroscopic, electrochemical, and flash-induced kinetic methods allows the mutants to be analyzed for influences both on cytochrome spectra and thermodynamic properties and on the kinetics of specific electron transfer reactions. The results show that none of the 5 residues is absolutely essential. Substitution of aspartate or valine for Gly48 results in the loss of photosynthetic growth. The G48V mutant assembles a bc1 complex, but with modified cytochromes bH and bL, and a dysfunctional quinone reductase (Qc) site; an alanine is tolerated at this position. Possibly, a small residue is important here for heme packing. Gln58 and Ser102 are the only highly conserved polar residues predicted to be within the transmembrane spans, apart from the histidines which are heme axial ligands. Neither Gln58 nor Ser102 is essential for assembly or function of the bc1 complex, although substitution of other amino acids in these positions does cause subtle, but measurable changes. Phe104 lies midway between the axial ligands to cytochromes bL and bH and can be modeled to project in the space separating the two hemes. Replacement of this highly conserved aromatic residue by isoleucine has no measurable influence on the rate of electron transfer through the cytochrome b chain containing the two hemes. Finally, Pro202 is a totally conserved proline which is in the middle of transmembrane helix D, in between the 2 histidines which provide ligands to the hemes. No major inhibition of electron transfer resulted from replacing this proline by a leucine, although subtle changes in spectra of the b cytochromes and their electrochemical properties were noted.
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PMID:Examination of the functional roles of 5 highly conserved residues in the cytochrome b subunit of the bc1 complex of Rhodobacter sphaeroides. 131 21

The c14CoS/c14CoS mouse has a homozygous deletion of about 1.2 cM on chromosome 7 that includes the albino (c) locus. The untreated 14CoS/14CoS newborn has been reported to exhibit a marked transcriptional activation of the hepatic NAD(P)H:menadione oxidoreductase (Nmo-1; DT diaphorase; quinone reductase; azo dye reductase) gene, as well as elevated UDP glucuronosyl-transferase (UGT1*06) and glutathione transferase (GT1) activities, when compared with the cch/cch wild-type and the cch/c14CoS heterozygote. We show here that the newborn hepatic activities of seven enzymes that play a role in the oxidative stress response--NMO1, UGT1*06, GT1, copper-zinc superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase--are increased 1.5- to 25-fold in 14CoS/14CoS, as compared with ch/ch and ch/14CoS mice. The activities of four additional enzymes having no known association with the oxidative stress response--benzo[a]pyrene hydroxylase (CYP1A1, cytochrome P(1)450), acetanilide 4-hydroxylase (CYP1A2, cytochrome P(3)450), lactate dehydrogenase (LDH), and NADPH-cytochrome c reductase--are not significantly different among the three genotypes. These data suggest that there exists an "oxidative stress" response in the untreated 14CoS/14CoS newborn. We postulate that a chromosome 7 regulatory gene, which we have named Nmo-1n, might encode a trans-acting negative effector of the Nmo-1 gene, and genes corresponding to the other elevated enzymic activities described above. When both copies of Nmo-1n are deleted, as is the case in 14CoS/14CoS mice, a battery of genes involved in oxidative stress is released from negative control and becomes activated--despite the absence of any apparent oxidative insult by foreign chemicals.
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PMID:"Oxidative stress" response in liver of an untreated newborn mouse having a 1.2-centimorgan deletion on chromosome 7. 154 Jan 61

Sulfide-dependent partial electron-transport reactions were studied in thylakoids isolated from cells of the cyanobacterium Oscillatoria limnetica, which had been induced to perform sulfide-driven anoxygenic photosynthesis. It was found that these thylakoids have the capacity to catalyze electron transfer, from sulfide to externally added quinones, in the dark. Assay conditions were developed to measure the reaction either as quinone-dependent sulfide oxidation (colorimetrically) or as sulfide-dependent quinone reduction (by UV dual-wavelength spectrophotometry). The main features of this reaction are as follows. (i) It is exclusively catalyzed by thylakoids of sulfide-induced cells. Noninduced thylakoids lack this reaction. (ii) Plastoquinone-1 or -2 are equally good substrates. Ubiquinone-1 and duroquinone yield somewhat slower rates. (iii) The apparent Km for plastoquinone-1 was 32 microM and for sulfide about 4 microM. Maximal rates (at 25 degrees C) were about 75 mumol of quinone reduced per mg of chlorophyll.h. (iv) The reaction was not affected by extensive washes of the membranes. (v) Unlike sulfide-dependent NADP photoreduction activity of these thylakoids, which is sensitive to all the specific inhibitors of the cytochrome b6f complex, the new dark reaction exhibited differential sensitivity to these inhibitors. 2-n-Nonyl-4-hydroxyquinoline-N-oxide was the most potent inhibitor of both light and dark reactions, working at submicromolar concentrations. 5-n-Undecyl-6-hydroxy-4,7-dioxobenzothiazole also inhibited the two reactions to a similar extent, but at 10 times higher concentrations than 2-n-nonyl-4-hydroxyquinoline-N-oxide. 2,5-Dibromo-3-methyl-6-isopropyl-p-benzoquinone, 2-iodo-6-isopropyl-3-methyl-2',4,4'-trinitrodiphenyl ether, and stigmatellin had no effect on the dark reaction at concentrations sufficient to fully inhibit the light reaction from sulfide. We propose that the sulfide-induced factor which enables the use of sulfide as the electron donor for anoxygenic photosynthesis in Oscillatria limnetica is a membrane-bound sulfide-quinone reductase. Its site of interaction is suggested to be either the cytochrome b6 (at the Qc quinone binding site or the bH site) or the plastoquinone pool. The analogy to other anoxygenic photosynthetic systems is discussed.
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PMID:Sulfide-induced sulfide-quinone reductase activity in thylakoids of Oscillatoria limnetica. 189 23


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