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:1.6.3.1 (NADPH oxidase)
11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic microsomes from rats fed a crude or a purified diet were compared by measureing their contents of protein, cytochrome P-450, and cytochrome b5, their rates of activity of NADPH- and NADH-cytochrome c reductases, NADPH-cytochrome P-450 reductase, NADPH oxidase, lipid peroxidase, ethylmorphine N-demethylase, aniline hydroxylase, benzpyrene hydroxylase, and their substrate-binding spectra (ethylmorphine, hexobarbital, aniline, and ethyl isoyanide). With the exception of lipid peroxidase activity, which was much higher in microsomes from animals fed the crude diet, little or no consistent diet-related differences in these measurements were observed over a 4-week experimental period, nor were results significantly less variable with one or the other diet. No consistent significant differences were observed with two strains of rats. The lower lipid peroxidase activity seen with the purified diet appeared to be due to the high vitamin E intake when that diet was employed; rats fed the crude diet and an oral supplement of alpha-tocopherol yielded microsomes with low lipid peroxidase activities similar to those seen in microsomes from rats fed the purified diet. A gradual temporal increase in benzpyrene hydroxylase activity was observed with both diets. This was interpreted to be due to environment inducing agents other than those present in the diet.
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PMID:Comparison of hepatic microsomal drug-metabolizing systems from rats fed crude and purified diets. 0 25

The addition of 125--1000 mM (NH4)2SO4 to rat hepatic washed microsomal preparations was found to stimulate markedly the rate of in vitro metabolism of the hepatocarcinogen dimethylnitrosamine. Solute treatment also stimulated the activities of NADPH-cytochrome c reductase, NADPH oxidase, the N-oxidation of N,N-dimethylaniline, and the fluorescent interaction of 8-anilino-1-naphthalenesulfonic acid (ANS) with hepatic microsomes. (NH4)2SO4 had a varied effect on the activities of a number of mixed-function oxidase (MFO) enzyme activities. Whereas the activities of aniline 4-hydroxylase and 4-nitrobenzoic acid nitroreductase were enhanced at all solute concentrations, several other MFO enzyme activities were either progressively inhibited or stimulated at low and inhibited at high (NH4)2SO4 concentrations. Solute treatment had no effect on microsomal cytochrome P-450 content but inhibited the activities of glucose 6-phosphatase and UDP-glucuronyltransferase. All of the observed changes in enzyme activities and ANS-microsome fluorescence interaction were found to be reversible when the solute was removed by centrifugation. These findings suggest that (NH4)2SO4 and certain other solutes can reversibly modify the conformation of microsomal membranes in such a manner as to affect microsomal enzyme activities.
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PMID:The effect of ammonium sulfate on the metabolism of dimethylnitrosamine and other xenobiotics by rat hepatic microsomes. 3 91

The lipid composition of rat liver microsomes was not altered in response to a single acute dose of ethanol relative to isocaloric glycerol-treated controls. Microsomal cytochrome P-450 was transiently elevated, the elevation paralleling blood ethanol levels. Microsomal NADPH oxidase was transiently elevated relative to the activity in isocaloric glycerol-treated controls.
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PMID:Effect of an acute dose of ethanol on rat liver microsomal mixed function oxygenase components and membrane lipid composition. 35 56

The electrophilic properties of the quinone-hydroquinone configuration of anthracycline antibiotics suggests a possible influence on cytochrome P-450-mediated mono-oxygenase reactions. Both doxorubicin and triferric-doxorubicin (a derivative in which the quinone groups are blocked with iron) showed a similar dose-dependent inhibition of liver microsomal drug metabolism. A doxorubicin concentration-related stimulation of NADPH oxidase activity was found to be linear but that for triferric-doxorubicin was asymptotic. Neither inhibitor affected the activity of cytochrome c reductase, cytochrome b5 reductase or cytochrome P-450 reductase. However, doxorubicin did potentiate the inhibitory effect of aniline on cytochrome P-450 reductase and on ethylmorphine metabolism. It is concluded that these anthracyclines inhibit drug metabolism in vitro not by their electron-withdrawing potential but in a manner more similar to that described for type II compounds.
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PMID:Inhibition of drug oxidation and stimulation of NADPH oxidase in vitro by doxorubicin and triferric-doxorubicin. 51 68

The effect of glucagon on the components of the hepatic microsomal electron transport chain (NADPH oxidase, NADPH cytochrome c reductase (EC 1.6.2.4), cytochrome P-450, and NADPH cytochrome P-450 reductase), and on two representative oxidative pathways (aminopyrine N-demethylation, a type I substrate oxidation; and aniline p-hydroxylation, a type II substrate oxidation) was determined. Microsomes from rats pretreated with glucagon (300 mug/kg per day for 3 days) showed a significant decrease in NADPH oxidation and in aminopyrine N-demethylation with a prolonged hexobarbital sleeping time, and a significant increase in aniline p-hydroxylation. Microsomes from rats pretreated with a lower dose of glucagon (30 mug/kg per day for 3 days) showed a significant decrease in the microsomal N-demethylation of aminopyrine. Glucagon had no effect when added in vitro to microsomes, suggesting that the in vivo effects of glucagon are mediated indirectly in the intact animal.
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PMID:Alterations of hepatic microsomal drug metabolism by glucagon. 81 38

The report by Schacter et al. (J Biol Chem 247: 3601, 1972) that an antibody to NADPH-cytochrome c oxidoreductase inhibited NADPH-cytochrome c reductase and heme oxygenase activities in rat and pig liver and spleen microsomes demonstrated the role of this flavoprotein in microsomal heme oxygenation. Recent studies from other laboratories (Yoshida et al., J Biochem 75, 1187: 1974 and Bissell et al., Fed Proc 33: 1246, 1974) have strongly suggested that cytochrome P-450 is not involved in heme oxygenation. The availability of a homogeneous preparation of NADPH-cytochrome c reductase prompted us to test heme oxygenase activity in a system devoid of hemoprotein contamination. NADPH-cytochrome c reductase catalyzed biliverdin formation at a rate of 8.26 +/- 0.5 SEM nmole min-1mg-1 in the absence of biliverdin reductase. The rate of bilirubin formation in the presence of biliverdin reductase was less than 10% of the rate of biliverdin formation, suggesting that mixture of biliverdin isomers may be produced. Biliverdin production was potently (70--80%) inhibited by catalase, but was unaffected by superoxide dismutase. Epinephrine also inhibited heme oxygenation, presumably by utilizing O2. required for the formation of H2O2 by the reductase. By extrapolation, the NADPH oxidase activity due to NADPH-cytochrome c reductase can account for heme degradation occurring in microsomes. However, the specificity of ring scission at the IXalpha position must be due to another microsomal protein, perhaps the heme oxygenase of Yoshida et al., and not cytochrome P-450.
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PMID:The catalysis of heme degradation by purified NADPH-cytochrome C reductase in the absence of other microsomal proteins. 82 31

The activity of the hepatic microsomal ethanol-oxidizing system (MEOS) was compared with the content of three forms of cytochrome P-450. Measurements were also made of the activity of microsomal reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the enzyme which generates H2O2 in microsomes and which has been considered by some to be the rate-limiting step of MEOS activity. Ethanol feeding to rats for 4 to 5 weeks significantly enhanced the activities of MEOS and NADPH oxidase by 102 and 62%, respectively. Concomitantly, form I of cytochrome P-450 was increased by 88% (P less than .001). Acute administration of a large dose of ethanol to animals pretreated chronically with ethanol enhanced MEOS activity by 21% (P less than .05), whereas NADPH oxidase activity remained unchanged. In addition, an acute dose of ethanol enhanced form I of cytochrome P-450 by 20% (P less than .05); thus its increase was comparable to that of MEOS activity. Pretreatment of rats with phenobarbital increased the specific activity of microsomal NADPH oxidase by 40% (P less than .05) but not that of MEOS. By contrast, CCl4 administration to rats diminished MEOS activity by 33% (P less than .01), whereas NADPH oxidase activity remained unchanged. The CCl4 treatment was found to decrease significantly all three forms of cytochrome P-450: form I by 45%, form II by 56% and form III by 24%. These results suggest that in the presence of NADPH microsomes oxidize ethanol to acetaldehyde by a process which involves, at least in part, the form I of cytochrome P-450 and in which H2O2 generation by NADPH oxidase is not the rate-limiting step.
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PMID:Hepatic microsomal ethanol-oxidizing system (MEOS): dissociation from reduced nicotinamide adenine dinucleotide phosphate oxidase and possible role of form I of cytochrome P-450. 115 72

Radiometric methods for the assay of deoxycorticosterone 11beta-hydroxylase and for the determination of NADP on a microscale were developed. The determination of NADP was based on the quantitative conversion of 6-phospho[1-14C]gluconate to 14CO2 by the action of 6-phosphogluconate dehydrogenase. Using these methods NADPH oxidase activity of the adrenodoxin reductase-adrenodoxin system as well as kinetic properties of deoxycorticosterone 11beta-hydroxylase (cytochrome P-450) were investigated. The NADPH oxidase activity observed in the presence of adrenodoxin reductase, adrenodoxin, and O2, but in the absence of cytochrome P-450 and deoxycorticosterone, were functions of O2 and adrenodoxin concentrations and represented the autooxidation of reduced adrenodoxin which resulted in the production of H2O2. Due to the rapid autooxidizability of reduced adrenodoxin, only a small fraction of electrons conveyed from NADPH to adrenodoxin by way of adrenodoxin reductase was utilized for the deoxycorticosterone 11beta-hydroxylase reaction under the conditions employed.
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PMID:Enzymic studies on adrenocortical deoxycorticosterone 11beta-hydroxylase system. 117 57

1. Lindane administered to untreated rats or rats pretreated with phenobarbital (PB) or 3-methylcholanthrene (MC) increased liver lipid peroxidation, of the same magnitude in all groups. 2. PB pretreatment produced a 50% increase in lipid peroxidation (TBAR) by liver homogenates and microsomes, an effect accompanied by increases in cytochrome P-450, NADPH-cytochrome P-450 reductase, NADPH oxidase and microsomal superoxide anion production, MC pretreatment resulted in increases in liver cytochrome P-450 and NADPH oxidase only. 3. Pretreatment of rats with PB, but not MC or lindane, gave increases in glutathione peroxidase and reductase. 4. Pretreatment with PB, but not MC, increased liver GSH. Lindane decreased liver GSH to the same extent as PB plus lindane. 5. Biliary GSH, GSSG and bile flow were decreased by lindane to similar extents in all groups. 6. Lindane induced periportal necrosis with haemorrhagic foci in all groups. 7. Data presented indicate that the early lipid peroxidative response of liver to lindane was unchanged by PB- or MC-stimulated hepatic microsomal enzyme induction.
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PMID:Effect of phenobarbital and 3-methylcholanthrene on the early oxidative stress component induced by lindane in rat liver. 172 29

1. The monooxygenase and oxidase activities of liver microsomes from phenobarbital (PB)-treated rabbits were investigated for their dependence on the high spin shift (delta alpha) of the ferric cytochrome P-450 induced by a series of benzphetamine analogues. 2. The spin shift activity of the substrate determines, via the first electron transfer kinetics, the steady-state level of the reaction intermediate oxycytochrome P-450. Correlation of the amount or oxycytochrome P-450 with delta alpha can be experimentally proved. 3. The spin-state-dependent formation of oxycytochrome P-450 regulates quantitatively the rates of NADPH oxidation and substrate N-demethylation. Both activities correlate with delta alpha. Oxycytochrome P-450 is substrate-stabilized towards decay with the formation of O2- which, upon dismutation, gives rise to H2O2. 4. The ratio of N-demethylase to NADPH oxidase activity (coupling ratio) also increases with the spin shift, delta alpha. Concomitantly, the proportion of NADPH accounted for by H2O2 and H2O formation via two- and four-electron reduction of dioxygen decreases. This indicates that the substrate-induced structural changes in the enzyme active centre which give rise to spin transition may likewise modify the coupling properties. 5. Perfluorinated compounds, which fail to undergo monooxygenation, fall in line with the benzphetamine derivatives with respect to the dependence of NADPH oxidation rate and steady-state oxycytochrome P-450 level on delta alpha. The increased oxidase activity results mostly in H2O formation. 6. The leakiness of the PB-induced monooxygenase pathway in the biotransformation of oxygen in the presence of the benzphetamines and perfluorinated compounds does not result in marked increases in H2O2 formation. Therefore, the increase of NADPH oxidase activity by these substrates does not significantly enhance H2O2-mediated oxygen tissue toxicity.
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PMID:Cytochrome P-450 spin state and leakiness of the monooxygenase pathway. 184 83


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