Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.6 (NADPH oxidase)
 10,295 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver microsomes of the rat contain a group of hydroxylating enzymes which are coupled to a greater or lesser degree to the electron flow system. In our studies, enzymes believed to be directly associated with the electron flow chain of NADPH, ferricyanide reduction, cytochrome c, cytochrome P-450 and substrate hydroxylation have been observed in livers obtained from normal, tumor-bearing and whole body irradiated rats as well as in Morris hepatoma 7777 and dimethyl-amino-biphenyl induced breast tumors.A significant difference appeared to exist in the activity of NADPH oxidase, NADP-ferricyanide reductase and benzopyrene hydroxylase when normal liver was compared with the liver obtained from a breast-tumor-bearing animal. Both cytochrome P-450 and cytochrome b(5) were decreased in the tumor-bearing animal.Tissue distribution of benzopyrene hydroxylase in normal, lactating and tumor-bearing Wistar rats has been studied.With the exception of NADPH oxidase, the activities of NADP-cytochrome c reductase, NADPH-ferricyanide reductase, benzopyrene hydroxylase and P-450 were markedly different in liver from Morris hepatoma 7777-bearing Buffalo rat when this was compared with homologous tissue obtained from normal Buffalo rat.Whole-body irradiated animals showed increased P-450 and NADPH oxidase activity in liver as a function of irradiation and there further appeared to be a correlation with decreased ferricyanide reductase activity.
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PMID:Mixed-function oxidation in tumors. 439 26

Microsomal electron transport components (NADPH oxidase, NADPH-ferricyanide reductase, cytochromes P-450 and b(5)) have been studied in Buffalostrain rat liver and in a series of Morris hepatomata (9618A-2, 7800, 7795 and 7787). Normal liver values differed significantly from those measured in livers of tumourbearing animals. In all hepatomata per se, very low levels were found.
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PMID:Further studies of electron transport components in a series of Morris hepatoma-bearing rats. 440 Dec 92

A membrane-bound NADPH-cytochrome c reductase, which is capable of forming the superoxide anion (O2-) in the presence of menadione, was highly purified from membrane fractions of disrupted guinea pig polymorphonuclear leukocytes by solubilization with 0.2% Triton X-100 and chromatographies on Sephacryl S-300 and 2',5'-ADP-agarose. The overall purification from the membrane fraction was over 110-fold, with a yield of about 6%. The purified preparation did not contain two other pyridine nucleotide-oxidizing enzymes: NADH- and NAD(P)H-oxidizing enzymes (J. Biochem. 94, 931-936, 1983). Besides cytochrome c, the purified enzyme was able to reduce menadione, Nitroblue tetrazolium (NBT) and 2,6-dichlorophenolindophenol. The reduction of menadione alone resulted in the formation of O2-. The purified enzyme preparation contained FAD. When assayed by measuring O2--generation in the presence of menadione, the enzyme showed an optimum pH at 7.0-7.4, and Km values for NADPH, NADH, and menadione were 25, 230, and 5.3 microM, respectively. The enzyme activity was not inhibited by NaN3 or dicumarol, but was by N-ethylmaleimide, EDTA, and quercetin; these inhibition profiles agree with those observed for the NADPH oxidase in the membrane fraction of phorbol-myristate acetate-stimulated leukocytes. Furthermore, when compared by means of the NBT-staining method combined with disc gel electrophoresis, the purified enzyme was electrophoretically indistinguishable from the NADPH-NBT reductase in the plasma membrane as well as phagosomes of the leukocytes. These results suggest that the purified NADPH-cytochrome c reductase is the putative flavoprotein of the NADPH oxidase system responsible for the respiratory burst.
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PMID:Purification and characterization of a membrane-bound NADPH-cytochrome c reductase capable of catalyzing menadione-dependent O2- formation in guinea pig polymorphonuclear leukocytes. 609 21

Superoxide (O-2) production by partially purified NADPH oxidase from guinea pig neutrophils was markedly increased when the cells were activated by exposure to phorbol-myristate acetate. On the contrary, NADPH-dependent cytochrome c and 2,6-dichlorophenolindophenol (DCIP) reductase activities in preparations from resting and activated neutrophils were similar. The apparent Km values for NADH and NADPH of the reductase activities were different from those of the O-2 producing enzyme. The electron acceptors did not inhibit the oxygen consumption by NADPH oxidase in the presence of superoxide dismutase. Even in anaerobiosis the oxidase failed to reduce cytochrome c and DCIP. These results suggest that NAD(P)H-dependent dye reductase activities are not involved in the electron transport system responsible for the O-2 production by neutrophils.
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PMID:NADPH oxidase of neutrophils forms superoxide anion but does not reduce cytochrome c and dichlorophenolindophenol. 632 73

Superoxide generation, assessed as the rate of acetylated cytochrome c reduction inhibited by superoxide dismutase, by purified NADPH cytochrome P-450 reductase or intact rat liver microsomes was found to account for only a small fraction of their respective NADPH oxidase activities. DTPA-Fe3+ and EDTA-FE3+ greatly stimulated NADPH oxidation, acetylated cytochrome c reduction, and O(2) production by the reductase and intact microsomes. In contrast, all ferric chelates tested caused modest inhibition of acetylated cytochrome c reduction and O(2) generation by xanthine oxidase. Although both EDTA-Fe3+ and DTPA-Fe3+ were directly reduced by the reductase under anaerobic conditions, ADP-Fe3+ was not reduced by the reductase under aerobic or anaerobic conditions. Desferrioxamine-Fe3+ was unique among the chelates tested in that it was a relatively inert iron chelate in these assays, having only minor effects on NADPH oxidation and/or O(2) generation by the purified reductase, intact microsomes, or xanthine oxidase. Desferrioxamine inhibited microsomal lipid peroxidation promoted by ADP-Fe3+ in a concentration-dependent fashion, with complete inhibition occurring at a concentration equal to that of exogenously added ferric iron. The participation of O(2) generated by the reductase in NADPH-dependent lipid peroxidation was also investigated and compared with results obtained with a xanthine oxidase-dependent lipid peroxidation system. NADPH-dependent peroxidation of either phospholipid liposomes or rat liver microsomes in the presence of ADP-Fe3+ was demonstrated to be independent of O(2) generation by the reductase.
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PMID:Superoxide generation by NADPH-cytochrome P-450 reductase: the effect of iron chelators and the role of superoxide in microsomal lipid peroxidation. 633 20

NADPH-dependent oxygen utilization by liver microsomal fractions was stimulated by the addition of increasing concentrations of butylated hydroxyanisole concomitant with the inhibition of benzphetamine N-demethylase activity. The apparent conversion of monooxygenase activity to an oxidase-like activity in the presence of the antioxidant was correlated with the partial recovery of the reducing equivalents from NADPH in the form of increased hydrogen peroxide production. The progress curve of liver microsomal NADPH oxidase activity in the presence of butylated hydroxyanisole displayed a lag phase indicative of the formation of a metabolite capable of uncoupling the monooxygenase activity. Ethyl acetate extracts of microsomal reaction mixtures obtained in the presence of butylated hydroxyanisole, oxygen, and NADPH stimulated the NADPH oxidase activity of either liver microsomes or purified NADPH-cytochrome c (P-450) reductase. Using high performance liquid chromatography, gas chromatography, and mass spectrometry techniques, two metabolites of butylated hydroxyanisole, namely t-butylhydroquinone and t-butylquinone, were identified. The quinone metabolite and/or its 1-electron reduction product interact with the flavoprotein reductase to directly link the enzyme to the reduction of oxygen which results in an inhibition of the catalytic activity of the cytochrome P-450-dependent monooxygenase.
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PMID:Butylated hydroxyanisole-stimulated NADPH oxidase activity in rat liver microsomal fractions. 641 52

NADPH-dependent ubiquinone-1 reductase activity was present in the phagocytic vesicles of pig polymorphonuclear leucocytes. The apparent Km-value of the reductase for NADPH was 29 microM which is similar to that of the NADPH-dependent superoxide formation. Increase of the quinone-reductase activity by increasing the concentrations of ubiquinone-1 was associated with the decrease of the superoxide forming activity, the rate of the NADPH oxidation being constant independent of the quinone concentration. p-Chloromercuribenzoate inhibited both superoxide formation and reduction of the quinone, whereas low concentrations of cetyltrimethylammonium bromide which inhibit the superoxide formation did not inhibit the reduction of the quinone. The reduction of 2,6-dichlorophenolindophenol which has been shown not to be inhibited by both inhibitors. The quinone-reductase activity could be extracted with a mixture of deoxycholate and Tween 20 which extracts the superoxide forming activity. The observations indicate that a region of the superoxide-forming NADPH oxidase between a mercurial-sensitive site and a site sensitive to the cationic detergent is responsible for the reduction of ubiquinone.
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PMID:NADPH-dependent reduction of ubiquinone-1 associated with the superoxide-forming oxidase of pig polymorphonuclear leucocytes. 642 94

The superoxide (O2.-)-forming enzyme NADPH oxidase from pig neutrophils was solubilized and partially purified by gel-filtration chromatography. The purification procedure allowed the separation of NADPH oxidase activity from NADH-dependent cytochrome c reductase and 2,6-dichlorophenol-indophenol reductase activities. O2.-forming activity was co-purified with cytochrome b-245 and was associated with phospholipids. However, active fractions endowed with cytochrome b were devoid of ubiquinone and contained only little FAD. The cytochrome b/FAD ratio was 1.13:1 in the crude solubilized extract and increased to 18.95:1 in the partially purified preparations. Most of FAD was associated with fractions containing NADH-dependent oxidoreductases. These results are consistent with the postulated role of cytochrome b in O2.-formation by neutrophil NADPH oxidase, but raise doubts about the participation of flavoproteins in this enzyme activity.
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PMID:Composition of partially purified NADPH oxidase from pig neutrophils. 643 85

Spironolactone pretreatment (10mg/100g, twice daily for 4 days, orally) caused a significant decrease in cytochrome P-450 levels in the liver microsomes in female rats but male rats were unaffected. NADH oxidase activity was significantly decreased in both sexes by this pretreatment but NADPH oxidase and NADH cytochrome C reductase activities were not altered. NADPH cytochrome c reductase activity was increased more markedly in female rats. Despite the decrease in P-450 levels, aminopyrine N-demethylase activity was increased in female rats, while it remained unchanged in males. 7-Ethoxycoumarin O-deethylase activity was markedly increased in male and slightly decreased in female rats. The azoreductase activity was slightly reduced in treated male rats and remained unaltered in female rats when it was expressed in activity per mg microsomal protein, but the activity did show a significant increase in female rats when it was expressed as a P-450 specific rate. Sex associated differences in the effect of spironolactone on the rat liver microsomal drug metabolizing enzyme system demonstrated in the present study cannot be simply explained by the previously reported effect on adrenal and testicular steroids in male rats. It also seems unlikely that these effects were caused by an alteration in P-450 quality by selective destruction of certain species of P-450.
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PMID:Effect of spironolactone on hepatic microsomal monooxygenase and azoreductase activities. 707 90

For most commonly used mouse strains there is either no sex difference in drug metabolism, or females have a higher rate of metabolism than males of the same strain. In the CRL:CD-1 strain, for example, the males have a lower Vmax and a higher Km than females for ethylmorphine N-demethylation. By contrast, kinetic analysis for this pathway of drug metabolism in the BALB/cJ mouse strain demonstrated that males have a higher Vmax and a lower Km than females. Although gonadal hormones appear to play a similar role in both the strains with respect to body weight, liver weight, microsomal protein content, and the weights of sex hormone responsive organs, a strict dependence of the sex differences in ethylmorphine (EM) metabolism on gonadal hormones could not be demonstrated. A systematic analysis of the spectral interactions of EM with cytochrome P-450 (P-450), the activities of NADPH P-450 reductase and NADPH oxidase in these mouse strains did not reveal a common regulatory site for gonadal hormones. Moreover, sex differences in EM N-demethylase activity are not a direct function of the total P-450 present in hepatic microsomes since, for both strains, males have higher P-450 content than females. We conclude, therefore, that sex differences in hepatic EM N-demethylase activity in the BALB/cJ and CRL:DC-1 mouse strains may depend on the relative quantities of the individual forms of microsomal P-450 which appear to be under genetic and/or hormonal control.
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PMID:Effects of endogenous sex hormones on mouse liver ethylmorphine N-demethylase. 721 71


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