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)

Administration of phenobarbital to rats over a period of 5 days was shown to increase hepatic lipid peroxidation concomitant with induction of cytochrome P-450 and cytochrome c reductase. The purpose of this study was to determine whether the increase in lipid peroxidation was due to a lowering in hepatic antioxidants. The results show that increased lipid peroxidation was not due to a decreased level of antioxidants since the fat-soluble antioxidants were unchanged and ascorbate, a water-soluble antioxidant, was elevated. The relationship of the increase in hepatic ascorbate to enhanced lipid peroxidation is discussed.
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PMID:Effects of phenobarbital administration on levels of physiological antioxidants in rat liver. 73 93

Malate dehydrogenase, reputed to be a soluble matricial enzyme, is shown to be also strongly associated with the inner membrane, in pig heart mitochondria. Repeated sonications, water washes, freezing-thawing cycles are not very effective to remove malate dehydrogenase activity from inner membranes, which whatever the treatment, remains important. This activity is only partly solubilized by the substrates, malate or oxaloacetate. High ionic strength treatments by either NaCl-carbonate or 3M KCl have a strong effect, but they also remove cytochrome c oxidase and rotenone-sensitive NADH-cytochrome c reductase, reputed inner membrane intrinsic enzymes, thus strongly damaging the inner membrane. After the action of phospholipase A from Naja Naja Venom, the residual activity is about twenty per cent and only phosphatidyl choline and phosphatidyl ethanolamine decreased significantly, the other phospholipids being unchanged. It is suggested that the enzyme is deeply buried in the membrane and mainly interacts with phosphatidyl choline.
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PMID:The markers of pig heart mitochondrial sub-fractions. II. - On the association of malate dehydrogenase with inner membrane. 75 79

Experiments were conducted on 45 male rats; histophysiological characteristics of ependymocytes of the subcommissural organ (SCO) and of adrencorticocytes of the glomerular zone of the adrenal cortex (GZA) was investigated under conditions of dehydration and water loading. A marked activation of H-6-PDH, HDH, NAD-dependent alphaHPDH, and an enhancement of the H-6-PDH, NAD-diaphorase and 3betaol activity in the GZA adrencorticocytes resulted from dehydration. Water loading depressed the synthetic processes, particularly in the SCO ependymocytes. The data obtained suggest a functional interrelation between the SCO and GZA.
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PMID:[Histophysiological characteristics of the structures of the subcommissural organ of the brain and the glomerular zone of the adrenal gland in changes of the water-electrolyte balance]. 88 35

In rats given 15% solution of ethyl alcohol (v/v) instead of drinking water adlibitum for eight months, histochemical analysis showed a dictinct fall in activities of the oxidative enzymes (succinate and lactate dehydrogenases, DPNH-diaphorase) in the centro-acinar cells of the pancreas and in the islets of Langerhans.
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PMID:Chronic alcoholism and the pancreas. 103 49

1. Anti-heart mitochondria autoantibodies were developed in serum from dogs following experimental myocardial infarction. 2. Heart mitochondria frozen and thawed repeatedly in a sucrose/Tris-chloride buffer retained both their functional integrity as measured by the respiratory control ratio and their ability to serve as an antigen in a complement fixation test. Mitochondria frozen and thawed in a potassium chloride/Tris-chloride buffer lost both their functional integrity and their autoantigenic activity after one freeze-thaw cycle. 3. Extraction of the heart mitochondria with acetone/water mixtures to remove phospholipids from the membrane led to a complete loss of the ability of the mitochondria to react in the complement fixation test but did not affect the ability of the membranes to bind autoantibody in absorption experiments. 4. Treatment of the mitochondrial membranes with increasing concentrations of trypsin caused a loss of up to approximately 50% of the membrane protein with a gradual decrease in the autoantigenic activity of the membrane without impairment of the ability of the membrane to bind autoantibody. 5. Removal of up to 90% of the sialic acid of the mitochondrial membrane with neuraminidase resulted in a considerable increase in the complement-fixing autoantigenic activity of the membrane without changing the apparent ability of the membrane to bind autoantibody in absorption experiments. 6. Exposure of mitochondrial membranes to autoantibody and complement caused an inhibition of both an inner mitochondrial membrane enzyme, i.e. cytochrome oxidase (48%) and an outer mitochondrial membrane enzyme, i.e. NADH cytochrome c reductase (rotenone insensitive) (37%).
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PMID:Characterization of autoantigenic sites on isolated dog heart mitochondria. 118 45

Using liposomes we have demonstrated an electron transfer between tocopherol (vitamin E) and cytochrome c. Reduced cytochrome c protects vitamin E from oxidation induced either directly by ultraviolet light or indirectly by soybean lipoxygenase-catalyzed oxidation of arachidonic acid. Oxidized cytochrome c is reduced by tocopherol and tocopherol homologues (chromanols) resulting in accumulation of tocopheroxyl radicals which we detected by ESR. The peak height of the ESR spectrum of tocopheroxyl radicals (which is proportional to the amount of radical present) is proportional to the ratio of reduced to oxidized cytochrome c. In mitochondrial membranes succinate-cytochrome c reduction is inhibited by antimycin A. Addition of exogenous chromanols facilitates a by-pass of the antimycin A blocked electron pathway, and succinate-dependent cytochrome c reductase activity is restored. Cytochrome c may act as a water-soluble complement to the lipid-soluble ubiquinol in regenerating mitochondrial tocopherol from tocopheroxyl radical.
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PMID:Electron transport between cytochrome c and alpha tocopherol. 132 44

The effect of selenium administered acutely or chronically on the hepatic microsomal drug-metabolizing system has been investigated in mice. After 72 h following acute administration of selenium (7.5 mg/kg, i.p.), there was a significant inhibition of the activities of aminopyrine (AM) N-demethylase and ethylmorphine (EM) N-demethylase, and cytochrome P-450 levels but no change in the activities of aniline (AN) hydroxylase, 7-ethoxycoumarin (EC) O-deethylase, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and reduced nicotinamide adenine dinucleotide (NADH)-ferricyanide reductase, and cytochrome b5 content. Chronic administration of selenium in the drinking water (1 or 2 ppm selenium) for 12 weeks, resulted in no alteration in any of the parameters measured. However, significant decreases in activities of AM N-demethylase and AN hydroxylase, and cytochrome P-450 levels were detected in animals given higher doses of selenium (4 or 8 ppm selenium). Following the in vitro additions of selenium to hepatic microsomes obtained from untreated mice, selenium inhibited the AM N-demethylase, AN hydroxylase and 7-EC O-deethylase in a concentration-dependent manner, but no alteration in NADPH-cytochrome c reductase and cytochrome P-450 levels was observed. These results indicate that selenium is a specific from inhibitor of hepatic monooxygenase.
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PMID:Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. 147 37

Nitroaniline mustards have potential as hypoxia-selective cytotoxic agents, with reductive metabolism activating the nitrogen mustard by converting the electron-withdrawing nitro group to an electron-donating hydroxylamine or amine. However, the parent compounds have poor aqueous solubility, and their potencies are limited by low reduction potentials (E1/2 ca. -600 mV versus the normal hydrogen electrode) and corresponding slow rates of nitro reduction. To address these limitations, a series of 4-nitroaniline mustards bearing hydrophilic side chains attached via an electron-withdrawing carboxamide group was prepared and evaluated for hypoxia-selective cytotoxicity against Chinese hamster cell lines. The N-[(N,N-dimethylamino)ethyl]carboxamide derivatives proved to have excellent aqueous solubility and improved cytotoxic potency, but their reduction potentials, while higher than the non-carboxamide compounds, were still low and little selectivity for hypoxic cells were observed. A series of carboxamides of 2,4-dinitroaniline mustard was also prepared. These compounds had reduction potentials in the desired range (E1/2 ca. -450 mV by cyclic voltammetry) and were more toxic to hypoxic than aerobic UV4 cells. The most selective compounds were 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide (20, SN 23862) and its water-soluble N-[(N,N-dimethylamino)ethyl]carboxamide analogue. These showed selectivities of 60- to 70-fold for hypoxic UV4 cells. The selectivity of 20 was much superior to that of its aziridine analogue (23, CB 1954), which was only 3.6-fold more toxic to hypoxic than oxic cells in the same system. Compound 20 is a much less efficient substrate than CB 1954 for the major aerobic nitroreductase from rat Walker tumor cells, NAD(P)H:quinone oxidoreductase (DT diaphorase). Lack of aerobic bioactivation of 20 by DT diaphorases may be responsible for its higher hypoxic selectivity than that of 23.
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PMID:Hypoxia-selective antitumor agents. 5. Synthesis of water-soluble nitroaniline mustards with selective cytotoxicity for hypoxic mammalian cells. 150 7

The structural gene of the Paracoccus denitrificans NADH-ubiquinone oxidoreductase encoding a homologue of the 75-kDa subunit of bovine complex I (NQO3) has been located and sequenced. It is located approximately 1 kbp downstream of the gene coding for the NADH-binding subunit (NQO1) [Xu, X., Matsuno-Yagi, A., and Yagi, T. (1991) Biochemistry 30, 6422-6428] and is composed of 2019 base pairs and codes for 673 amino acid residues with a calculated molecular weight of 73,159. The M(r) 66,000 polypeptide of the isolated Paracoccus NADH dehydrogenase complex is assigned the NQO3 designation on the basis of N-terminal protein sequence analysis, amino acid analysis, and immuno-cross-reactivity. The encoded protein contains a putative tetranuclear iron-sulfur cluster (probably cluster N4) and possibly a binuclear iron-sulfur cluster. An unidentified reading frame (URF3) which is composed of 396 base pairs and possibly codes for 132 amino acid residues was found between the NQO1 and NQO3 genes. When partial DNA sequencing of the regions downstream of the NQO3 gene was performed, sequences homologous to the mitochondrial ND-1, ND-5, and ND-2 gene products of bovine complex I were found, suggesting that the gene cluster carrying the Paracoccus NADH dehydrogenase complex contains not only structural genes encoding water-soluble subunits but also structural genes encoding hydrophobic subunits.
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PMID:Structural features of the 66-kDa subunit of the energy-transducing NADH-ubiquinone oxidoreductase (NDH-1) of Paracoccus denitrificans. 160 43

Bovine mitochondrial NADH-ubiquinone reductase (complex I), the first enzyme in the electron-transport chain, is a membrane-bound assembly of more than 30 different proteins, and the flavoprotein (FP) fraction, a water-soluble assembly of the 51-, 24-, and 10-kDa subunits, retains some of the catalytic properties of the enzyme. The 51-kDa subunit binds the substrate NAD(H) and probably contains both the cofactor, FMN, and also a tetranuclear iron-sulfur center, while a binuclear iron-sulfur center is located in the 24- or 10-kDa proteins. The 75-kDa subunit is the largest of the six proteins in the iron-sulfur protein (IP) fraction, and its sequence indicates that it too contains iron-sulfur clusters. Partial protein sequences have been determined at the N-terminus and at internal sites in the 51-kDa subunit, and the corresponding cDNA encoding a precursor of the protein has been isolated by using a novel strategy based on the polymerase chain reaction. The mature protein is 444 amino acids long. Its sequence, and those of the 24- and 75-kDa subunits, shows that mitochondrial complex I is related to a soluble NAD-reducing hydrogenase from the facultative chemolithotroph Alcaligenes eutrophus H16. This enzyme has four subunits, alpha, beta, gamma, and delta, and the alpha gamma dimer is an NADH oxidoreductase that contains FMN. The gamma-subunit is related to residues 1-240 of the 75-kDa subunit of complex I, and the alpha-subunit sequence is a fusion of homologues of the 24- and 51-kDa subunits, in the order N- to C-terminal. The most highly conserved regions are in the 51-kDa subunit and probably form parts of nucleotide binding sites for NAD(H) and FMN. Another conserved region surrounds the sequence motif CysXXCysXXCys, which is likely to provide three of the four ligands of a 4Fe-4S center, possibly that known as N-3. Characteristic ligands for a second 4Fe-4S center are conserved in the 75-kDa and gamma-subunits. This relationship with the bacterial enzyme implies that the 24- and 51-kDa subunits, together with part of the 75-kDa subunit, constitute a structural unit in mitochondrial complex I that is concerned with the first steps of electron transport.
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PMID:Relationship between mitochondrial NADH-ubiquinone reductase and a bacterial NAD-reducing hydrogenase. 190 Jan 94


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