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)

Six patients (4 women and 2 men, age between 60 and 90 years), subjected to right hemicolectomy, were gut donors. The mucosa was isolated from the last portion of the ileum and the first portion of the colon. Tissue specimens were free from pathological changes. The activities of the enzymes of phase I (NADPH cytochrome c reductase, ethoxycoumarin O-deethylase, aminopyrine N-demethylase, microsomal epoxide hydrolase, cytosolic epoxide hydrolase, glutathione reductase and glutathione peroxidase) and the enzymes of phase II (glutathionetransferase, glucuronyltransferase, acetyltransferase, thioltransferase, sulphotransferase and glyoxalase) were measured in the microsomal or cytosolic fractions obtained from ileum and colon mucosa. The activity in the ileum was higher than in the colon for NADPH cytochrome c reductase (p less than 0.05) and cytosolic epoxide hydrolase (p less than 0.001) (phase I enzymes), and glutathionetransferase (p less than 0.02), sulphotransferase (p less than 0.05) and glyoxalase (p less than 0.02) (phase II enzymes). The other enzymes had similar activities in two mucosa. The distribution pattern of drug metabolizing enzymes cannot be considered as a single pattern in human ileum and colon because of the observed enzyme-dependent differences.
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PMID:Profile of drug-metabolizing enzymes in human ileum and colon. 272 51

The ability of selenium (Se) to act as a redox catalyst is an important factor in understanding the biological function of selenoproteins in addition to that of GSH peroxidase. Selenocystine at micromolar levels exhibited pseudothiotransferase activity by enhancing the reduction of 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB) by thiols. In contrast, selenite inhibited the reduction of DTNB by thiols. Selenite was more catalytic than selenocystine in the reduction of cytochrome c by GSH, whereas GSH peroxidase was a weak catalyst. Tissues from Se-deficient and Se-supplemented rats were assayed for activities of GSH-thiotransferase, NADPH cytochrome c reductase, formaldehyde dehydrogenase, and a hypothesized GSH cytochrome c reductase. GSH-thiotransferase activity was significantly increased in the liver of Se-deficient rats. No appreciable activity of this enzyme was found in the kidney of rats from either dietary group. No enzymatic activity for cytochrome c reduction by GSH was detected in cytosols, mitochondria, or microsomes from liver and kidney of Se-deficient or Se-supplemented rats. Formaldehyde dehydrogenase was significantly higher in liver cytosols from Se-supplemented rats than from Se-deficient rats. The higher activity was not attributed to Se-containing proteins, but to an unknown small molecular-weight factor. This study did not support the hypothesis that physiological levels of Se may be involved in sulfhydryl-disulfide exchange reactions in vivo, or that selenium may enhance cytochrome c reduction by GSH in vivo.
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PMID:Selenium as a sulfhydryl redox catalyst and survey of potential selenium-dependent enzymes. 282 Nov 93

A 40% reduction of the diameter of the ascending aorta maintained for 60 days induced the formation of a compensate cardiac hypertrophy in rabbits without changing the value of the azide insensitive Ca2+-ATPase activity in comparison to control hearts. The cardiac mitochondria isolated from constricted animals assayed in presence of glutamate and succinate did not show a change in the R.C.I. and ADP/O values in comparison to the controls, whilst the QO2 value enhanced or decreased respectively when determined with glutamate or succinate. The intramuscular injections of CoQ10 (12 mg/kg body weight/48 h) enhanced the mitochondrial CoQ10 concentrations both in the control and in the constricted animals and further increased the QO2 value determined in both groups of animals when glutamate was used as the substrate. The production of O2.- radicals by the level of the complexes I and III of the respiratory chain, did not change in the constricted animals, nor in the animals administered with CoQ10 in comparison to the control. CoQ10 augmented the rate of oxygen consumption by the submitochondrial particles only in the constricted animals. Moreover, the treatment with the coenzyme or the constriction of the aorta, did not modify the cardiac superoxide dismutase activity, but increased the glutathione peroxidase activity only in the banded animals. In addition, in the CoQ10 treated animals there was a reduction of NADH-diaphorase activity both in the control and constricted animals, while the malondialdehyde, generated during the thiobarbituric acid test, and the cardiac content of lipofuscin were decreased.
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PMID:The effect of treatment with coenzyme Q10 on the mitochondrial function and superoxide radical formation in cardiac muscle hypertrophied by mild aortic stenosis. 303 17

Preexposure of rats to sublethal levels of hyperoxia or ozone reduces morbidity and mortality when the animals are subsequently exposed to lethal levels of either oxidant stress. Lung homogenates and isolated type II pneumocytes from rats exposed to these oxidant stresses demonstrate enhanced antioxidant enzyme activities. Antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase are responsible for the detoxification of partially reduced oxygen species, superoxide and hydrogen peroxide, to less reactive states. Potential pulmonary cellular loci of partially reduced oxygen include mitochondrial NADH dehydrogenase, endoplasmic reticulum-derived NADPH cytochrome c reductase, and cytosolic xanthine oxido reductase. Thus partially reduced oxygen species are hypothesized to mediate hyperoxia and ozone-induced pulmonary damage. This damage may be attenuated by enhanced intracellular antioxidant enzyme activities. Pharmacologic augmentation of pulmonary antioxidant enzymes may be accomplished via intratracheal or intravascular delivery of liposomes containing antioxidant enzymes. Rats pretreated with liposomes containing both superoxide dismutase and catalase, when subsequently exposed to lethal levels of hyperoxia, demonstrate enhanced survival compared with control animals or with animals treated with control liposomes or native antioxidant enzymes. Finally, knowledge obtained from in vitro investigations optimizing liposomal delivery to specific pulmonary cell types may further aid in reducing in vivo pulmonary damage to hyperoxia and ozone.
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PMID:Pulmonary metabolism of reactive oxygen species. 306 93

The influence of chronic adriamycin treatment on cellular defence mechanisms against free radicals has been determined in rats. To that end, the changes in vitamin E content, activity of superoxide dismutase, catalase and factors of the glutathione system were measured in heart, kidneys and liver after 24 and 52 days of treatment. Moreover, damage was assessed by measuring the activity of NADPH- and NADH-cytochrome c reductase. The results concerning the components of the oxidative defence systems in male rats showed reductions in the activity of superoxide dismutase and catalase in renal tissue and in factors of the glutathione system in liver tissue. In cardiac tissue an increased activity of catalase and elevated content of total glutathione were found. Vitamin E content was increased in liver and to a lesser extent, in kidneys. The activity of Se-dependent glutathione peroxidase sharply decreased only in liver. Major differences between male and female rats were not observed in renal and cardiac tissue, as far as protective factors were concerned. However, a decrease in catalase activity was detectable earlier in male kidneys. The protective factors in liver of female rats were far less susceptible to in vivo treatment with adriamycin, as compared to liver of male rats. Decreased activity of the cytochrome reductases was found in liver of male rats. In male renal tissue only cytochrome c reductase activity was significantly reduced. Male cardiac tissue showed no signs of biochemical damage, although from histological examination in a parallel study [J Natl Cancer Inst 76: 299-307 (1986)] lesions were evident. In female rats no damage was found in liver, kidneys and heart.
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PMID:The effect of chronic adriamycin treatment on heart kidney and liver tissue of male and female rat. 337 82

Hepatocyte cytotoxicity caused by substituted benzoquinones was associated with increased cytosolic Ca2+ concentration. p-Benzoquinone-induced hepatotoxicity was enhanced when the hepatocytes were loaded with Ca2+ by preincubation with ATP. A similar order of potency of the substituted benzoquinones in releasing Ca2+ from isolated mitochondria and inducing hepatocyte cytotoxicity was found; in decreasing order, this was 2-Br-, unsubstituted-, 2-CH3-, 2,6-(CH3O)2-, 2,6-(CH3)2-, 2,5-(CH3)2-, 2,3,5-(CH3)3-, and 2,3,5,6-(CH3)4-benzoquinones (duroquinone). The cellular products of quinone metabolism, hydroquinones and glutathione conjugates, did not cause mitochondrial Ca2+ release. Benzoquinone-induced mitochondrial Ca2+ release was preceded by GSH conjugate formation and NAD(P)H oxidation but followed by mitochondrial swelling. With duroquinone, a slow GSH and NADPH oxidation preceded Ca2+ release, but GSH oxidation did not occur with Se-deficient mitochondria lacking glutathione peroxidase activity. Cyanide-insensitive respiration was also observed with duroquinone but not with benzoquinone, suggesting that duroquinone undergoes redox cycling. GSH was depleted by both arylation and oxidation with 2,6-(CH3O)2-, 2,6-(CH3)2-, 2,5(CH3)2-, and 2,3,5-(CH3)3-benzoquinones. Benzoquinone concentrations that totally depleted GSH did not cause Ca2+ release until intramitochondrial NAD(P)H was oxidized. Ca2+ release was also prevented when NAD(P)H generation was stimulated by the presence of isocitrate or 3-hydroxybutyrate. This suggests that mitochondrial Ca2+ release is associated with NAD(P)H oxidation catalyzed by NADH dehydrogenase with benzoquinone or by the glutathione peroxidase-glutathione reductase system with duroquinone.
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PMID:Quinone toxicity in hepatocytes: studies on mitochondrial Ca2+ release induced by benzoquinone derivatives. 342 29

Thirty-six wild-caught woodchucks (Marmota monax) were characterized according to sex, weight, trapping locality, liver pathology, and serum or hepatic markers of woodchuck hepatitis virus. Liver subcellular fractions were assayed for microsomal cytochromes P-450, aryl hydrocarbon hydroxylase, glutathione, cytosolic enzymes involved in its metabolism (glutathione S-transferase, glutathione peroxidase, and glutathione reductase), in the hexose monophosphate shunt (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), NADH- and NADPH-dependent diaphorases, and DT diaphorase. Moreover, liver postmitochondrial fractions were assayed for their ability to activate procarcinogens [i.e., a tryptophan pyrolysate product, aflatoxin B1, 2-aminofluorene, and trans-7,8-dihydrobenzo(a)pyrene] to mutagenic metabolites in the Ames reversion test and to decrease the activity of direct-acting mutagens [i.e., 4-nitroquinoline N-oxide, 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine X 2HCl, and sodium dichromate]. A considerable interindividual variability in metabolism was observed among the examined woodchucks. Some of the investigated parameters were more elevated in virus carriers, especially in those suffering from chronic active hepatitis, but only a few of the recorded differences (i.e., oxidized glutathione reductase and NADPH-dependent diaphorase) were statistically significant. The comparison of the monitored activities in woodchucks and in other rodent species (rat and mouse) led to the conclusion that the liver metabolism of mutagens and carcinogens in woodchucks is more oriented in the sense of activation, while detoxification mechanisms are more efficient in rats and mice.
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PMID:Metabolism of mutagens and carcinogens in woodchuck liver and its relationship with hepatitis virus infection. 360 50

Male Wistar rats were exposed to 4 ppm nitrogen dioxide (NO2) for 10 d, and at intervals alveolar macrophages were collected by pulmonary lavage. A metabolic enhancement of alveolar macrophages was observed on d 4 of exposure. The specific activities of glucose-6-phosphate dehydrogenase and glutathione peroxidase of the peroxidative metabolic pathway increased to 1.29-fold (p less than 0.001) and 1.17-fold (p less than 0.05) those of the control values, respectively. The specific activities of succinate-cytochrome c reductase of the mitochondrial respiratory system and pyruvate kinase of the glycolytic pathway also increased to 1.17-fold (p less than 0.01) and 1.20-fold (p less than 0.01) those of the control values, respectively. In addition, the incorporation of [3H]leucine and [14C]thymidine into alveolar macrophages were elevated to 1.77-fold (p less than 0.001) and 1.84-fold (p less than 0.01) those of the control values, respectively. The activities of all enzymes tested decreased to control levels by d 10. The number of alveolar macrophages collected from exposed animals increased to 1.24-fold (p less than 0.01) that of the control value on d 7 and was maintained at a significantly higher level until d 10. Alveolar macrophages were heterogeneous in size (7-21 micron in diameter), and most of them were distributed between 11 and 17 micron in diameter. Exposures to 4 ppm NO2 increased significantly the cells of 9-13 micron in diameter on the seventh day. These results show that exposures to 4 ppm NO2 cause a metabolic enhancement and subsequent increase in alveolar macrophages.
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PMID:Activation and increment of alveolar macrophages induced by nitrogen dioxide. 395 12

The location of peroxide-utilizing enzymes has been studied in rat brain. Glutathione peroxidase and glutathione reductase distributions indicate that both enzymes are located in the cytoplasm and in the matrix space of "synaptosomal" and "free" mitochondria. On the other hand, catalase distribution parallels that of NADH-cytochrome c reductase (rotenone-insensitive), and appears to be associated with the outer membrane of brain mitochondria. Whereas no gross age-dependent changes in various marker enzymes were found, a gradual but significant increase in glutathione peroxidase from the soluble fraction of free mitochondria was detected. The consequences of such increase are discussed with regard to the reducing potential of the cell.
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PMID:Age-dependent variations in peroxide-utilizing enzymes from rat brain mitochondria and cytoplasm. 622 5

This investigation examined the effect of the anthracycline antitumor agents on reactive oxygen metabolism in rat heart. Oxygen radical production by doxorubicin, daunorubicin, and various anthracycline analogues was determined in heart homogenate, sarcoplasmic reticulum, mitochondria, and cytosol, the major sites of cardiac damage by the anthracycline drugs. Superoxide production in heart sarcosomes was significantly increased by anthracycline treatment; for doxorubicin, the reaction appeared to follow saturation kinetics with an apparent Km of 112.62 microM, required NADPH as cofactor, was accompanied by the accumulation of hydrogen peroxide, and probably resulted from the transfer of electrons to molecular oxygen by the doxorubicin semiquinone after reduction of the drug by sarcosomal NADPH:cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4). Superoxide formation was also significantly enhanced by the anthracycline antibiotics in the mitochondrial fraction. Doxorubicin stimulated mitochondrial superoxide formation in a dose-dependent manner that also appeared to follow saturation kinetics (apparent Km of 454.55 microM); however, drug-related superoxide production by mitochondria required NADH rather than NADPH and was significantly increased in the presence of rotenone, which suggested that the proximal portion of the mitochondrial NADH dehydrogenase complex [NADH:(acceptor) oxidoreductase, EC 1.6.99.3] was responsible for the reduction of doxorubicin at this site. In heart cytosol, anthracycline-induced superoxide formation and oxygen consumption required NADH and were significantly reduced by allopurinol, a potent inhibitor of xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2). Reactive oxygen production was detected in all of our studies despite the presence of both superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and glutathione peroxidase (glutathione:hydrogen peroxide oxidoreductase, EC 1.11.1.9) in each cardiac fraction. These results suggest that free radical formation by the anthracycline antitumor agents, which occurs in the same myocardial compartments that are subject to drug-induced tissue injury, may damage the heart by exceeding the oxygen radical detoxifying capacity of cardiac mitochondria and sarcoplasmic reticulum.
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PMID:Effect of anthracycline antibiotics on oxygen radical formation in rat heart. 629 97


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