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

---

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

The soluble hydrogenase (hydrogen: NAD+ oxidoreductase, EC 1.12.1.2) from Alcaligenes eutrophus H 16 was purified 68-fold with a yield of 20% and a final specific activity (NAD reduction) of about 54 mumol H2 oxidized/min per mg protein. The enzyme was shown to be homogenous by polyacrylamide gel electrophoresis. Its molecular weight and isoelectric point were determined to be 205 000 and 4.85 respectively. The oxidized hydrogenase, as purified under aerobic conditions, was of high stability but not reactive. Reductive activation of the enzyme by H2, in the presence of catalytic amounts of NADH, or by reducing agents caused the hydrogenase to become unstable. The purified enzyme, in its active state, was able to reduce NAD, FMN, FAD, menaquinone, ubiquinone, cytochrome c, methylene blue, methyl viologen, benzyl viologen, phenazine methosulfate, janus green, 2,6-dichlorophenoloindophenol, ferricyanide and even oxygen. In addition to hydrogenase activitiy, the enzyme exhibited also diaphorase and NAD(P)H oxidase activity. The reversibility of hydrogenase function (i.e. H2 evolution from NADH, methyl viologen and benzyl viologen) was demonstrated. With respect to H2 as substrate, hydrogenase showed negative cooperativity; the Hill coefficient was n = 0.4. The apparent Km value for H2 was found to be 0.037 mM. The absorption spectrum of hydrogenase was typical for non-heme iron proteins, showing maxima (shoulders) at 380 and 420 nm. A flavin component could be extracted from native hydrogenase characterized by its absorption bands at 375 and 447 nm and a strong fluorescense at 526 nm.
...
PMID:Purification and properties of soluble hydrogenase from Alcaligenes eutrophus H 16. 18 26

Peripheral blood leukocytes from patients given corticosteroid or radiation therapy, as well as patients with bacterial or viral infections, were studied with regard to the selected enzyme activities of the hexose monophosphate shunt (HMS). Glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase (6-PGD) and reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase were assayed spectrophotometrically on mixed leukocyte suspensions in isotonic glycerol. Enzyme activities of G-6PD and NADPH oxidase in patients receiving corticosteroid or radiation therapy were significantly lower than the enzyme activity of 6-PGD. In patients with bacterial infections, activities of the three enzymes increased but in patients with viral infections, only the activities of NADPH oxidase and G-6PD were slightly decreased. Nitroblue tetrazolium (NBT) dyereducing activities of neutrophils from patients receiving corticosteroid or radiation therapy were attenuated which coincides with the reduced activities of HMS enzymes. From these results, it is likely that the reduced activities of intraleukocytic HMS enzymes of patients receiving corticosteroid or radiation therapy are correlated with intracellular bactericidal activities which might result from the attenuated level of hydrogen peroxide production.
...
PMID:The metabolic and phagocytic activities of leukocytes from patients receiving corticosteroid and radiation therapy, and patients with bacterial infections. 117 10

The mechanism by which the yeast form of Blastomyces dermatitidis resists killing by human peripheral blood polymorphonuclear neutrophils (PMN) was investigated. The metabolic products of the oxidative burst generated during the interaction of PMN and B. dermatitidis or Candida albicans were detected by lucigenin- or luminol-enhanced chemiluminescence (CL). Interaction of PMN and C. albicans resulted in luminol-enhanced CL 100-fold greater than that generated by PMN and B. dermatitidis. This correlated with killing of C. albicans and resistance of B. dermatitidis. Since B. dermatitidis and PMN interactions resulted in significant lucigenin-enhanced CL, deficient luminol CL was not due to a lack of products from the NADPH oxidase system. Killed B. dermatitidis cells at 37 degrees C were more efficient than live cells in stimulating PMN for luminol-enhanced CL; however, only fragmented B. dermatitidis cells elicited luminol-enhanced CL equivalent to that of C. albicans. Since lysates of PMN were active in a cell-free hydrogen peroxide-peroxidase-halide system, resistance of B. dermatitidis to PMN was not due to a defect in PMN peroxidase. Taken together, these findings indicate that resistance of B. dermatitidis to killing by PMN results from inefficient generation of products from the peroxidase-dependent PMN microbicidal system.
...
PMID:A basis for resistance of Blastomyces dermatitidis killing by human neutrophils: inefficient generation of myeloperoxidase system products. 132 54

Several types of compound exert their cytotoxicity by generating reactive oxygen species, notably the superoxide anion radical. These include quinoid and nitroaromatic compounds serving as redox cyclers, i.e. producing superoxide at the expense of NADPH and oxygen catalyzed by cellular reductases. In specialized cell-types employed in defense such as granulocytes, eosinophils and macrophages, myeloperoxidase, NADPH oxidase and nitric oxide synthase have been identified as major sources of reactive oxygen species in cell toxicity. These include hypochlorite, singlet oxygen, superoxide, nitric oxide and hydrogen peroxide. The interaction of superoxide and nitric oxide generates further oxidants such as peroxynitrite. Lumino-amplified chemiluminescence generated by Kupffer cells is partially sensitive to inhibitors of NO synthase. Superoxide dismutase has been found to catalyze a novel reaction, the reversible conversion of nitric oxide to the nitroxyl anion, the latter being viewed as another form of EDRF. In the defense against oxidative damage, there are enzymatic and nonenzymatic antioxidants. Regarding compounds used pharmacologically, we have been interested in ebselen, a seleno-organic compound exhibiting GSH peroxidase activity, which protects against reactive oxygen species generated, for example, at reoxygenation following a period of hypoxia. Further, we have studied lipoate and dihydrolipoate as antioxidant redox system and as singlet oxygen quencher, e.g. protecting against damage of deoxyguanosines in plasmid DNA generated by singlet oxygen.
...
PMID:Role of reactive oxygen species in cell toxicity. 133 81

The effect of hyperoxia (1-14 days, 85% O2) on rat alveolar macrophage and alveolar type II cell oxidant and antioxidant characteristics was investigated. Unstimulated control macrophages (2 h ex vivo) released hydrogen peroxide at a rate of 3.5 +/- 1.3 nmol/min mg protein-1, which was a cyanide-sensitive process. H2O2 release from alveolar macrophages decreased slightly but not significantly after 1 day in hyperoxia and increased significantly after 3 days (180%, p less than .05) and 14 days (380%, p less than .01). When H2O2 release was expressed as nmol from total macrophages per animal, the increase after 14 days in hyperoxia was 760%. H2O2 generation by hyperoxic macrophages was cyanide resistant, indicating the involvement of active NADPH oxidase. In both control and hyperoxic macrophages H2O2 release could be significantly stimulated with phorbol myristate acetate (PMA). Comparisons of H2O2 release by freshly isolated alveolar macrophages and alveolar type II cells must be cautiously interpreted because some cell functions may change during the isolation procedure. Freshly isolated (6 h ex vivo) control alveolar type II cells were found to generate H2O2 at a rate of 0.26 +/- 0.05 nmol/min mg protein-1. In type II cells H2O2 release, calculated as nmol/mg protein, decreased during the first 7 days of hyperoxia to 10% (p less than .01) of the control value and then returned back up to the control level after 14 days. A similar decrease was observed if H2O2 release was calculated as nmol/cell number. H2O2 release from control and hyperoxic type II cells was cyanide sensitive. The decrease in H2O2 release in type II cells was associated with cell membrane injury (as assessed by electron microscopy), while biochemical markers of cellular injury (trypan blue exclusion and cellular high-energy phosphates ATP, ADP) were unchanged. The ability of type II cells to scavenge extracellular H2O2 did not change in acute hyperoxia, but it increased significantly during the second week in hyperoxia. These results indicate that macrophages but not type II cells are stimulated to produce H2O2 during prolonged exposure to hyperoxia.
...
PMID:Hydrogen peroxide release from alveolar macrophages and alveolar type II cells during adaptation to hyperoxia in vivo. 139 11

Human leukocytes stimulated by opsonized zymosan increase their NADPH oxidase-catalysed reduction of molecular oxygen. This leads to enhanced formation of superoxyl radicals and subsequently hydrogen peroxide. The leukocyte enzyme myeloperoxidase generates the strong microbicidal oxidant hypochlorite from hydrogen peroxide and chloride anions. Hypochlorite inactivates serum alpha 1-proteinase inhibitor, a protein which protects host tissue from digestion by proteinases, that are also secreted by stimulated leukocytes. Micromolar concentrations of a water-soluble, quaternary ammonium analogue of alpha-tocopherol (vitamin E) (3,4-dihydro-6-hydroxy-N,N,N-2,5,7,8-heptamethyl-2H-1-benzopyran-2 -ethanaminium 4-methylbenzenesulfonate) and its tertiary amine derivative (3,4-dihydro-2- (2-dimethylaminoethyl)-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol hydrochloride) were able to protect alpha 1-proteinase inhibitor from inactivation by stimulated human leukocytes. The mechanism of action of the quaternary ammonium analogue was further investigated. Selective inhibition of hydrogen peroxide formation is assumed to be the reason for its protective effect. This compound rapidly reacts with superoxyl radicals, but not with hydrogen peroxide, and is only a weak hypochlorite scavenger. It neither impedes exocytosis of elastase, nor effectively inhibits NADPH oxidase or myeloperoxidase. In contrast, superoxide dismutase, which enhances hydrogen peroxide formation, cannot protect alpha 1-proteinase inhibitor from inactivation.
...
PMID:Leukocyte-mediated inactivation of alpha 1-proteinase inhibitor is inhibited by amino analogues of alpha-tocopherol. 165 88

Superoxide generation in the NADPH oxidase reaction of NADPH-cytochrome P-450 reductase, demonstrated using the ESR spin trap, 5,5-dimethyl-1-pyrroline-1-oxide, increased on the addition of lactoferrin. The NADPH-lactoferrin reductase activity was assessed in terms of NADPH oxidation and oxygen consumption. From Lineweaver-Burk plots, the Km and Vmax for lactoferrin were estimated to be 13 microM and 0.5 S-1, respectively. The liberation of iron from lactoferrin was proven with the use of bathophenanthroline and by the demonstration of bleomycin-dependent DNA degradation; lactoferrin was reduced by the enzyme in the presence of NADPH. During the reaction, the ESR spectrum of the spin trap adduct changed from one characteristic of DMPO-OOH to that of DMPO-OH. The conversion was ascribed to the reaction of hydrogen peroxide with reduced lactoferrin.
...
PMID:Lactoferrin-mediated formation of oxygen radicals by NADPH-cytochrome P-450 reductase system. 169 25

Brain nitric oxide synthase is a Ca2+/calmodulin-regulated enzyme which converts L-arginine into NO. Enzymatic activity of this enzyme essentially depends on NADPH and is stimulated by tetrahydrobiopterin (H4biopterin). We found that purified NO synthase contains enzyme-bound H4biopterin, explaining the enzymatic activity observed in the absence of added cofactor. Together with the finding that H4biopterin was effective at substoichiometrical concentrations, these results indicate that NO synthase essentially depends on H4biopterin as a cofactor which is recycled during enzymatic NO formation. We found that the purified enzyme also contains FAD, FMN and non-heme iron in equimolar amounts and exhibits striking activities, including a Ca2+/calmodulin-dependent NADPH oxidase activity, leading to the formation of hydrogen peroxide at suboptimal concentrations of L-arginine or H4biopterin.
...
PMID:Brain nitric oxide synthase is a biopterin- and flavin-containing multi-functional oxido-reductase. 171 90

Ancylostoma ceylanicum, the hookworm parasite of cat, dog and man, was found to contain NADH and/or NADPH oxidase as well as fumarate reductase activities. Both the enzyme systems were predominantly located in the membranes of mitochondrial-rich preparations. The membranes also exhibited the presence of a reduced pyridine nucleotide transhydrogenase activity which transferred hydrogen from NADPH to NAD. Amongst respiratory inhibitors, rotenone (Site I inhibitor) markedly depressed both NADH oxidase and fumarate reductase while others, namely antimycin-A, KCN and azide, had a lesser effect.
...
PMID:NADH oxidase and fumarate reductase of Ancylostoma ceylanicum. 175 94

Phagocytic leukocytes generate large amounts of reactive oxygen compounds during and after phagocytosis of micro-organisms. These compounds are essential for the killing of a wide variety of microbes. The enzyme responsible for this process is NADPH:O2 oxidoreductase (NADPH oxidase), which utilizes the reduction equivalents of NADPH to reduce atmospheric oxygen to superoxide (O2-.). Subsequently, superoxide is converted by the leukocytes to other reactive compounds, such as hydrogen peroxide (H2O2), hypochlorous acid (HOCl) and N-chloramines (RNCl). Each of these compounds has potent microbicidal properties. Under resting, non-phagocytizing conditions, phagocytes do not produce reactive oxygen compounds. However, within 15-30 sec after binding of micro-organisms to cell surface receptors, superoxide generation starts. This phenomenon is called the respiratory burst. This phenomenon is called the respiratory burst. The activation of the NADPH oxidase is caused by the assembly of components of this enzyme into an active complex. Under resting conditions, at least three components reside in the cytoplasm and at least two are located in the plasma membrane. Activation of the NADPH oxidase results in translocation of cytosolic components to the plasma membrane and formation of an active enzymatic complex in the plasma membrane.
...
PMID:The involvement of oxygen radicals in microbicidal mechanisms of leukocytes and macrophages. 179 94


1 2 3 4 5 6 7 8 9 10 Next >>

---