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)

15 min cold exposure of rats adapted to cold results in switching on a pathway of the fast oxidation of extramitochondrial NADH in the isolated liver mitochondria. This pathway is sensitive to mersalyl and cyanide, resistant to amytal and antimycin A, and can be stimulated by dinitrophenol. A portion of the endogenous cytochrome c pool can easily be removed by washing mitochondria of the cold-exposed rats. A scheme is discussed, postulating desorption of the inner membrane-bound cytochrome c into intermembrane space of mitochondria, resulting in formation of a link between the non-phosphorylating NADH-cytochrome c reductase in the outer mitochondrial membrane and cytochrome c oxidase in the inner membrane. It is suggested that such an oxidative pathway is involved in the urgent heat production in liver in response to the cold treatment.
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PMID:Activation of the external pathway of NADH oxidation in liver mitochondria of cold-adapted rats. 20 43

X-band electron-paramagnetic-resonance spectroscopy at 4.2--77K combined with measurements of oxidation-reduction potential was used to identify iron--sulphur centres in Arum maculatum (cuckoo-pint) mitochondria. In the oxidized state a signal with a derivative maximum at g = 2.02 was assigned to succinate dehydrogenase centre S-3. Unreduced particles showed additional signals at g = 2.04 and 1.98 (at 9.2 GHz), which may be due to a spin-spin interaction. In the reduced state a prominent signal at g = 1.93 and 2.02 was resolved into at least three components that could be assigned to centres S-1 and S-2 of succinate dehydrogenase (midpoint potentials -7 and -240 mV respectively at pH 7.2) and a small amount of centre N-1b (e'o= -240 mV) of NADH-ubiquinone reductase. In addition, changes in line shape around -10 mV indicated the presence of a fourth component in this signal. The latter was more readily reduced by NADH than by succinate, suggesting that it might be associated with the external NADH dehydrogenase. The iron-sulphur centres of NADH-ubiquinone reductase were present in an unusually low concentration, indicating that the alternative, non-phosphorylating, NADH dehydrogenase containing a low number of iron-sulphur centres may be responsible for most of the high rate of oxidation of NADH.
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PMID:Iron-sulphur centres in mitochondria from Arum maculatum spadix with very high rates of cyanide-resistant respiration. 59 30

The effects of the herbicide 4(2,4-dichlorophenoxy)butyric acid (2,4-DB) and fungicide N-(trichloromethyltio)-4-cyclohexene-1,2-dicarboximide (captan) on electron transport processes of mitochondria and chloroplasts have been investigated. Chloroplasts, isolated from spinach leaves (Spinacia oleracea L.), were treated with pesticide prior to the addition of electron acceptor and ADP. White potato (Solanum tuberosum L.) mitochondria were either incubated with pesticide before the addition of substrate, or they were treated with pesticide after the addition of substrate and ADP. Captan inhibited oxidation of malate by mitochondria and acted as an uncoupler. With succinate as sunstrate captan was found to stimulate state 4 respiration, as substrate captan was found to stimulate state 4 respiration, with the loss of coupled phosphorylation only at higher concentrations of fungicide. The herbicide 2,4-DB appeared to be 5 to 10 times less effective than captain. Both compounds inhibited phosphrylation-coupled succinate oxidation at higher concentrations and malate-coupled phosphorylation at lower concentrations. They acted as inhibitors of NADH-cytochrome c reductase. Both pesticides inhibited noncyclic electron transport in chloroplasts. The rate of ferricyanide reduction in the presence and absence of phosphorylating agents was reduced, and although the rate of ATP generation was reduced also, the P/2e ratio was not changed much under the influence of pesticides.
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PMID:Effects of the herbicide 2,4-DB and fungicide captan on reactions of mitochondria and chloroplasts. 126 87

We studied the possible relationships between the functional status of the beta-cell and activities or mRNA contents of enzymes involved in the catabolism of glucose. Three different in vitro models with attenuated insulin response were used: rat islets cultured at a low glucose concentration, rat islets incubated in vitro with streptozocin, and fetal rat islets. The fetal and streptozocin-administered islets were compared with adult islets cultured in RPMI-1640 containing 11 mM glucose, and the effects of the in vitro glucose concentrations (3.3, 11, and 28 mM) were assessed on adult islets only. Cellular mRNA levels for the mitochondrial DNA-encoded cytochrome b and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined by Northern-blot analysis. Enzymatic activities of high-Km (glucokinase) and low-Km (hexokinase) glucose-phosphorylating enzymes and succinate-cytochrome c reductase were also determined. Islets cultured at 3.3 mM glucose displayed a decreased activity of glucokinase compared with islets cultured at 28 mM glucose (23.3 +/- 12%), whereas there was no difference in hexokinase activity or the level of GAPDH mRNA. The activity of succinate-cytochrome c reductase was similar in islets cultured at the different glucose concentrations. The level of cytochrome b mRNA increased at 28 mM glucose compared with islets cultured at 11 mM glucose (140 +/- 14%). Islets incubated with streptozocin and subsequently cultured for 7 days at 11 mM glucose exhibited a decreased level of cytochrome b mRNA (65 +/- 5%) and no differences in the activities of glucokinase, hexokinase, succinate-cytochrome c reductase, or the level of GAPDH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exhibition of specific alterations in activities and mRNA levels of rat islet glycolytic and mitochondrial enzymes in three different in vitro model systems for attenuated insulin release. 164 83

Therapy with enzyme inducing drugs may improve glycemic control in patients with non-insulin-dependent diabetes mellitus. We evaluated the role of a mixed function oxidase system on glucose metabolism with an animal model. Rats were treated with an inducer (phenobarbital), an inhibitor (cimetidine) and a hepatotoxin (carbon tetrachloride) for a week to cause alterations in the liver. The mixed function oxidase system was assayed by determination of the cytochrome P-450 content and NADPH cytochrome c reductase in liver. Carbohydrate metabolism was evaluated by determining blood glucose, enzymes associated with glucose phosphorylation in the liver (glucokinase, hexokinase), glucose storage as glycogen and enzymatic delivery, glucose-6-phosphatase, and peripheral tissue by determining phosphorylating enzyme (hexokinase) and a key glycolytic enzyme (pyruvate kinase) and glycogen content in muscles. The therapy with the inducer enhanced glucose utilization in liver and storage in muscles. The inhibitor decreased the mixed function oxidase system, reduced glucose phosphorylating, but not gluconeogenetic enzymes, in the liver and increased glycolysis in muscles. Carbon tetrachloride, a hepatotoxin, impaired mixed function oxidase, glucose phosphorylating and delivering enzyme activity in liver, reduced blood glucose and caused glycogen accumulation in muscles. The function of liver microsomal enzyme system seems to be closely related to enzymatic glucose metabolism in the liver and muscles.
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PMID:Hepatic mixed function oxidase system and enzymatic glucose metabolism in rats. 304 Mar 22

A yeast strain (SP1) resistant to glucose repression modified simultaneously in the fermentative and in the oxidative pathways (loss of alcohol dehydrogenase I and over production of cytochrome a + a3, being insensitive to the glucose effect) developed a secondary mitochondrial hydrogen pathway. Oxidative phosphorylation was measured with exogenous NADH as substrate on mitochondria derived from repressed or derepressed cells. In this strain, antimycin A promotes a partial inhibition of NADH oxidation but a complete inhibition of phosphorylation. Amytal partially inhibits oxidation of NADH but not phosphorylation. KCN inhibits NADH oxidation in a biphasic way (first level 0.1 mM, second level 5 mM) but phosphorylation was fully inhibited by 0.1 mM KCN. This alternative but non-phosphorylating pathway is insensitive to salicyl hydroxamate. The external NADH dehydrogenase, like cytochrome c oxidase is partially insensitive to catabolite repression. These results provide evidence for the presence in strain SP1 of an alternative mitochondrial pathway, going from the external NADH dehydrogenase to an oxidase, different from the normal NADH dehydrogenase ubiquinone pathway.
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PMID:Evidence for an alternative and non-phosphorylating pathway for NADH reoxidation in a yeast strain resistant to glucose repression. 630 24

The reduction and the potential autoxidation of quinoid compounds may be viewed as taking place in three cell compartments. In microsomal fractions (endoplasmic reticulum) one-electron reduction by NAPDH-cytochrome P450 reductase leads to the formation of semiquinones which rapidly react with oxygen to form the parent quinone and superoxide anions. The formation of superoxide through this futile cycle leads ultimately to other damaging species (H2O2 and .OH). A similar futile cycle in mitochondria involves NADH dehydrogenase. In this instance, mitochondria initiation of such a cycle with quinones results not only in the formation of toxic radical species but also in the diversion of electrons from phosphorylating pathways. The consequent diminution of cellular ATP may have as important a consequence with respect to the toxicity of quinones as the generation of radicals. Finally, cytosolic DT diaphorase, which carries out a two-electron reduction of quinones to more stable hydroquinones, may compete with the one-electron systems and participate in the detoxification of quinones by supplying hydroquinones for conjugation reactions. The extent of quinone-induced damage may thus vary from cell to cell depending on the integration of these pathways.
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PMID:Futile redox cycling: implications for oxygen radical toxicity. 631 61

Erythrocyte ghost NADH dehydrogenase is inhibited in a competitive fashion by ATP and ADP whereas other nucleoside di- and triphosphates, cyclic nucleosides, as well as non-phosphorylating ATP analogs are relatively ineffective. In addition, this enzyme, measured with ferricyanide as electron acceptor, is inhibited by uncouplers of oxidative phosphorylation (proton-conducting reagents), the inhibition being competitive in character (i.e., the uncouplers were without influence upon maximum velocity). The effectiveness of the uncouplers was in the order of their hydrophobic character with the presence of the alkyl side chain rendering nonyl-dinitrophenol much more active than 2,6-dinitrophenol itself. Hydrophobic compounds that are not protonophores (e.g., eosin, proflavin or valinomycin) were not inhibitory. Whereas adenine nucleotides probably inhibit NADH oxidation competitively through structural similarity with the substrate, it appears unlikely that uncouplers compete at the NADH site directly. Rather, the apparently-competitive inhibition in the latter case may reflect competition for proton transfer to an acceptor residing in a hydrophobic region of the enzyme complex.
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PMID:Inhibition of erythrocyte plasma membrane NADH dehydrogenase by nucleotides and uncouplers. 650 43

1. Mitochondria were isolated from the spongy and compact ventricular myocardium of adult Thunnus thynnus thynnus L. 2. Measurement of the succinoxidase activity of phosphorylating mitochondria revealed that those from the spongy had an apparent Km being half of that of the mitochondria from the compact layer. These latter exhibited Km more sensitive to acidic pH values. 3. Succinate-cytochrome c reductase activity was very differently affected by pH and temperature in non-phosporylating mitochondria from the two cardiac layers. 4. The thermostability of the NADH-cytochrome c reductase and the succinate-cytochrome c reductase activities exhibited also marked differences in the two mitochondrial populations. 5. These results, which represent an example of metabolic zonation at the organelle level, are discussed in relation to the homeostatic cooperation of the two myocardial regions of tuna heart.
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PMID:Further characterization of two mitochondrial populations in tuna heart ventricle. 706 Mar 60

Phosphophoryns (PPs) are phosphoproteins specific to the dentin matrix and are the major noncollagenous matrix proteins in rat incisor dentin. It has been hypothesized that their phosphate groups are important in dentin mineralization. PPs have many sequences which are substrates for membrane-associated endogenous messenger-independent kinases. The objective of this study was to localize the protein kinases involved in phosphorylating the PPs. Osteoblast-like ROS 17/2.8 cells, which secrete extracellular matrix phosphoproteins, were lysed. After removal of the nuclei and mitochondria by low-speed centrifugation, the membrane associated organelles were isolated at higher speed from the cytosol. The Golgi vesicle and rough microsome fractions were collected from 29-43.7% sucrose density gradients. Each fraction was tested for casein kinase II (CKII) activity using an in vitro phosphorylation assay with PPs as substrate. To characterize and confirm the nature of the components of the sucrose gradient fractions, the activities of specific enzymes such as N-acetylglucosamine galactosyltransferase and cytochrome c reductase, which are exclusively associated with the Golgi and rough microsomes, respectively, were determined. Electron microscopy of the isolated fractions confirmed the enzyme assay characterizations. CKII activity capable of phosphorylating the PP was found in the rough microsome fraction but not in the Golgi. Thus, phosphorylation of the secreted phosphoproteins would appear to take place in the endoplasmic reticulum as a cotranslational event.
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PMID:Casein kinase localization in the endoplasmic reticulum of the ROS 17/2.8 cell line. 761 Sep 32


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