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)

Incubation of activated mouse peritoneal macrophages with tumor cell-conditioned medium (TCM) results in their deactivation, as measured by ability to release reactive oxygen intermediates and kill protozoal pathogens. The mechanism of suppression by macrophage deactivation factor (MDF) was studied. Inhibition of H2O2 release could not be overcome by increasing the concentration of phorbol diesters used to trigger the respiratory burst. Deactivated macrophages consumed H2O2 at the same rate as activated cells (t1/2, 35-40 min for 25 nmol H2O2 per 10(6) peritoneal cells). They transported glucose with the same kinetics (Km, 1 mM; Vmax, approximately 100 nmol per 6 min per milligram cell protein), and maintained similar intracellular concentrations of NADPH and NADP (approximately 0.62 mM and approximately 0.11 mM, respectively), as measured by enzymatic cycling methods and determinations of the volume of cell water (3.6 microliter/mg cell protein). To study the kinetics of the PMA-triggered NADPH oxidase in cell lysates, mixed detergents were used (deoxycholate and Tween 20). These stabilized the oxidase for approximately 3.3-fold longer than deoxycholate alone, which was used in previous studies. Incubation of activated macrophages in MDF resulted in a marked increase in the Km of the oxidase for NADPH, from 0.06 mM to 0.67 mM. The Vmax fell approximately 1.7-fold. These kinetic changes, together with the measured intracellular concentration of NADPH, account quantitatively for the suppression of H2O2 release by deactivated macrophages, and are nearly the mirror image of the kinetic changes observed during macrophage activation.
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PMID:Macrophage deactivation. Altered kinetic properties of superoxide-producing enzyme after exposure to tumor cell-conditioned medium. 302 Jan 51

A comparison has been made of the metabolic shifts in human and guinea pig leukocytes when they phagocytize. Respiration of guinea pig polymorphonuclear leukocytes (PMN) and the increment during phagocytosis were each about 2(1/2)-fold that of human PMN. This was also true of the direct oxidation of glucose-6-P (hexose monophosphate shunt). Enzymes potentially responsible for these phenomena have been compared in each species. Cyanide-insensitive NADH oxidase and NADPH oxidase were measured and only the formed exhibited adequate activity to account for the respiratory stimulus durintg phagocytosis. The hydrogen peroxide formed by this enzyme stimulates the hexose monophosphate shunt by oxidizing glutathione which upon reduction by an NADPH-linked glutathione reductase provides NADP to drive the hexose monophosphate shunt. Other linkages between respiratory stimulation and that of the hexose monophosphate shunt also pertain in the guinea pig.
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PMID:Respiration and glucose oxidation in human and guinea pig leukocytes: comparative studies. 439 48

Phagocytosis by rabbit alveolar macrophages (AM) is accompanied by increases in O(2) consumption, glucose oxidation, and H(2)O(2) formation. Two aspects of the interrelations between these metabolic features of phagocytosis have been studied.First, the following evidence indicates that glutathione, glutathione reductase, and peroxidase serve as a cytoplasmic shuttle between H(2)O(2) and NADPH-dependent glucose oxidation: (a) AM contain 5.9 mmumoles of reduced glutathione per 10(6) cells and exhibit glutathione peroxidase and NADPH-specific glutathione reductase activity; (b) oxidized glutathione potentiates NADP stimulation of glucose oxidation; (c) an artificial H(2)O(2)-generating system stimulates glucose oxidation; (d) the cell penetrating thiol inhibitor, N-ethylmaleimide diminishes glucose oxidation. This effect largely depends on inhibition of the glutathione system rather than on inhibition of either H(2)O(2) formation or enzymes directly subserving glucose oxidation.Second, three potential H(2)O(2)-generating oxidases have been sought. No cyanide-insensitive NADH or NADPH oxidase activity could be detected. D-amino acid oxidase activity was 0.48 +/-0.07 U/10(6) cells with D-alanine as substrate.
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PMID:Glutathione-dependent peroxidative metabolism in the alveolar macrophage. 439 62

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

1. Aerobically grown yeast having a high activity of glyoxylate-cycle, citric acid-cycle and electron-transport enzymes was transferred to a medium containing 10% glucose. After a lag phase of 30min. the yeast grew exponentially with a mean generation time of 94min. 2. The enzymes malate dehydrogenase, isocitrate lyase, succinate-cytochrome c oxidoreductase and NADH-cytochrome c oxidoreductase lost 45%, 17%, 27% and 46% of their activity respectively during the lag phase. 3. When growth commenced pyruvate kinase, pyruvate decarboxylase, alcohol dehydrogenase, glutamate dehydrogenase (NADP(+)-linked) and NADPH-cytochrome c oxidoreductase increased in activity, whereas aconitase, isocitrate dehydrogenase (NAD(+)- and NADP(+)-linked), alpha-oxoglutarate dehydrogenase, fumarase, malate dehydrogenase, succinate-cytochrome c oxidoreductase, NADH-cytochrome c oxidoreductase, NADH oxidase, NADPH oxidase, cytochrome c oxidase, glutamate dehydrogenase (NAD(+)-linked), glutamate-oxaloacetate transaminase, isocitrate lyase and glucose 6-phosphate dehydrogenase decreased. 4. During the early stages of growth the loss of activity of aconitase, alpha-oxoglutarate dehydrogenase, fumarase and glucose 6-phosphate dehydrogenase could be accounted for by dilution by cell division. The lower rate of loss of activity of isocitrate dehydrogenase (NAD(+)- and NADP(+)-linked), glutamate dehydrogenase (NAD(+)-linked), glutamate-oxaloacetate transaminase, NADPH oxidase and cytochrome c oxidase implies their continued synthesis, whereas the higher rate of loss of activity of malate dehydrogenase, isocitrate lyase, succinate-cytochrome c oxidoreductase, NADH-cytochrome c oxidoreductase and NADH oxidase means that these enzymes were actively removed. 5. The mechanisms of selective removal of enzyme activity and the control of the residual metabolic pathways are discussed.
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PMID:The kinetics of enzyme changes in yeast under conditions that cause the loss of mitochondria. 566 Jun 27

In order to resolve discrepancies in the literature concerning the subcellular localization of NADPH oxidase, we disrupted human neutrophils by nitrogen cavitation and fractionated the subcellular organelles on a discontinuous sucrose density gradient. The lightest fraction was 20- to 40-fold enriched for plasma membranes as determined by the marker enzymes alkaline phosphatase and phosphodiesterase I as well as by the ratio of lipid phosphorus to protein. There was a significant decrease in the specific activities of the granule markers myeloperoxidase, lysozyme, and beta-glucuronidase. An intermediate fraction was enriched in membrane markers but not to the extent the lightest fraction was enriched. This fraction contained more granular contamination, as shown by the marker enzymes. In contrast, the densest bands of the gradient were enriched for granule markers with little contamination by plasma membrane. Superoxide generation and NADP formation were primarily associated with the two membrane-enriched fractions from polymorphonuclear leukocytes stimulated with phorbol myristate acetate. The NADP formation associated with a dense granule fraction observed previously in our laboratory was probably due to a cyanide-stimulated oxidation of NADPH by myeloperoxidase.
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PMID:Co-localization of superoxide generation and NADP formation in plasma membrane fractions from human neutrophils. 609 76

The subcellular distribution of the superoxide-forming enzyme in horse polymorphonuclear leukocytes was investigated. After activation of the cells with sodium oleate, a relatively stable and NAD(P)H-dependent oxygen consumption and superoxide production was found in association with the plasma membranes. The pH dependence displayed an optimum near neutrality. The apparent Km values were 38 x 10(-6) mol/l for NADPH and 1,560 x 10(-6) mol/l for NADH, suggesting that NADPH is the physiological donor. The rates of oxygen uptake, O2- production, and NADP consumption were consistent with the stoichiometry: 2 O2 + NADPH leads to 2 O2- + NADP. The failure to demonstrate an increase of NAD(P)H-dependent oxidative activity in the cellular fractions that the investigated NADPH oxidase is identical with the enzyme responsible for the respiratory burst in phagocytizing leukocytes.
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PMID:Subcellular localization and properties of the NAD(P)H oxidase from equine polymorphonuclear leukocytes. 630 78

This laboratory has recently reported that, in a reconstituted enzyme system containing alcohol-induced isozyme 3a of liver microsomal cytochrome P-450, the sum of acetaldehyde generated by the monooxygenation of ethanol and of hydrogen peroxide produced by the NADPH oxidase activity is inadequate to account for the O2 and NADPH consumed. Studies on the stoichiometry have revealed the occurrence of an additional reaction involving an overall 4-electron transfer to molecular oxygen which is presumed to yield water: O2 + 2 NADPH + 2H+----2 H2O + 2 NADP+. The occurrence of a peroxidase reaction in which free H2O2 is reduced to water by NADPH was ruled out. When the 4-electron oxidase activity is taken into account, measurements of NADPH oxidation and O2 consumption are in accord with the amounts of products formed in the presence of various P-450 isozymes, either in the absence or presence of typical substrates, including those which undergo hydroxylation, N- or O-demethylation, or oxidation of hydroxymethyl to aldehyde groups. Of the substrates examined, some had no effect on the oxidase reaction yielding hydrogen peroxide or the 4-electron oxidase reaction, some were inhibitory, and some were stimulatory, but the same substrate did not necessarily have the same effect on the two reactions.
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PMID:On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. 672 72

The relationship between glucose metabolism and the "respiratory burst" of phagocytosing polymorphonuclear leukocytes (PMN) was studied in a Renex 30-treated cell system of guinea pig PMN by a polarometric technique. Phagocytosing PMN were treated with a detergent (Renex 30) and recovery of respiratory activity was examined by addition of various concentrations of NADP and glucose-6-phosphate (G6P) to determine the availability of endogenously formed NADPH via the hexose monophosphate (HMP) pathway. The oxygen uptake by phagocytosing PMN ceased after the treatment with Renex 30 and was restored by the addition of NADP and G6P. Furthermore, the restoration of oxygen uptake was linearly proportional to the rate of NADPH formation on increase in either NADP or G6P concentration. Resting PMN showed no respiratory activity even in the presence of excess NADP and G6P, in which NADPH was formed at the same rate as in phagocytosing PMN. In a parallel experiment, recovery of respiratory activity was examined in the same system by addition of NAD and glyceraldehyde-3-phosphate (G3P) in that order to clarify whether the respiratory enzyme can utilize NADH formed via the glycolytic pathway. In contrast to the results in the NADPH-forming system, the addition of NAD and G3P induced slight oxygen uptake of Renex 30-treated PMN, but there was no difference in the oxygen uptake between resting and phagocytosis-activated PMN. The results indicated that the primary oxidase responsible for the "respiratory burst" is NADPH oxidase, and that its activity is coupled with glucose oxidation via the HMP pathway without the participation of other metabolic pathways such as glycolysis.
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PMID:Evidence that NADPH is the actual substrate of the oxidase responsible for the "respiratory burst" of phagocytosing polymorphonuclear leukocytes. 687 61

Chemical cross-linkage of the positively charged viologen N-methyl-N'-(aminopropyl)-4-4'-bipyridinium dibromide (APMV) to the enzyme ferredoxin-NADP+ reductase from the cyanobacterium Anabaena PCC 7119 has been performed using the carbodiimide 1-ethyl[3-(3-dimethylaminopropyl)]carbodiimide. 0.5-1 mol, depending on the preparation, is introduced for each mol enzyme. The residue involved in the covalent linkage with the viologen, Glu139, has been identified using HPLC separation of the modified proteolytic peptides and subsequent sequencing. Modification of the enzyme changes its catalytic specificity since it is able to react directly with oxygen; this is observed by a high NADPH oxidase activity, which is completely absent in the native enzyme. More important, this new enzymic activity is indicative of the intramolecular electron transfer between the natural redox cofactor FAD and the artificially introduced viologen. Electrons can also flow in the reverse direction, from the viologen to the FAD group, then to NADP+, when the reaction is performed using glassy-carbon electrodes to reduce the viologen. Cyclic voltammetry experiments have shown that there is a small catalytic current between the electrode and the enzyme which is not observed in the native enzyme.
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PMID:The covalent linkage of a viologen to a flavoprotein reductase transforms it into an oxidase. 758 6


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