Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used sensitive isotopic and fluorometric assay procedures to investigate reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H]oxidation in a particulate fraction derived from normal and chronic granulomatous disease leukocytes. Granules isolated from normal resting cells showed allosteric kinetics with regard to oxidation of either NADH or NADPH, so that no enzyme activity was observed at physiological concentrations of substrate. If the granules were isolated from cells that had previously phagocytized zymosan, normal hyperbolic kinetics were obtained, so that activity could now be observed at low levels of substrate. The activity towards NADPH was always substantially greater than that towards NADH at any given concentration of substrate. This alteration in kinetics with phagocytosis was not observed with the other granule enzymes, acid phosphatase or beta-glucuronidase, and thus appeared to be specific for the reduced pyridine nucleotide oxidase(s). In contrast, granules isolated from cells of patients with chronic granulomatous disease showed allosteric kinetics regardless of whether they were obtained from resting or phagocytizing cells, so that NADPH oxidation was not measurable at physiological concentrations of substrate. This defect in the oxidation of NADPH by granules isolated from phagocytizing chronic granulomatous disease cells was observed over the pH range of 4.0 to 7.0. These data suggest that initiation of the respiratory burst by pahgocytosis normally requires an allosteric transformation in a reduced pyridine nucleotide oxidase, which in turn allows expression of enzymatic activity at physiological concentrations of substrate. The defect in chronic granulomatous disease appears to lie in an inability to achieve this transformation, and the enzyme remains in the inactive, allosteric form.
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PMID:Allosteric transformation of reduced nicotinamide adenine dinucleotide (phosphate) oxidase induced by phagocytosis in human polymorphonuclear leukocytes. 2 57

Cocaine and its derivatives blunted responses of neutrophils (cell/cell aggregation, up-regulation of the receptor for C3bi (CR3, CD11b/CD18), generation of superoxide anion (O2-) and degranulation to various stimuli. The order of potency of these agents was the same as that for local anesthesia: tetracaine greater than bupivacaine greater than cocaine greater than lidocaine. Neutrophil aggregation elicited by the chemoattractant FMLP (10(-7) M) was inhibited by cocaine (10 mM) to 13.6 +/- 6% of control (p less than 0.002); the IC50 was approximately 4 mM. Cocaine and the other local anesthetics not only inhibited the upregulation of CR3 and O2- generation, but also blocked degranulation of cytochalasin B-treated cells. Cocaine (10 mM) reduced beta-glucuronidase and lysozyme secretion to 4.3 +/- 0.7 and 13 +/- 2.2% controls, respectively; its IC50 was 4 mM. Local anesthetics added after ligand/receptor engagement (FMLP) interrupted aggregation and halted generation of O2-. Moreover, local anesthetics rapidly inhibited aggregation, O2- generation, and degranulation elicited by PMA (1 microgram/ml) or the Ca ionophore A23187 (10 microM): the effects of cocaine could therefore not be attributed to unique actions at the FMLP receptor. Peak levels of intracellular Ca2+ ([Ca]i) at 5 to 10 s, and levels of [Ca]i 120 s after FMLP in Fura 2-loaded cells were significantly lower in cells treated with lidocaine, findings that could be explained by enhanced 45Ca2+ efflux from neutrophils. In cells loaded with bis(carboxyethyl)carboxyfluorescine (pH indicator) local anesthetics failed to affect the initial FMLP-induced (0 to 15 s) drop of pHi but inhibited the later (120 s) realkalinization of the cytosol (lidocaine, bupivacaine). Most remarkably, autoradiographs of SDS gels prepared from stimulated, 32P-labeled neutrophils treated with local anesthetics showed no difference from resting cells, either with respect to patterns of phosphorylation and dephosphorylation or their kinetics. Labeling of a 47-kDa protein, a component of the reduced nicotinamide-adenine dinucleotide phosphate-oxidase system, was unchanged. The effects of local anesthetics, which blunt neutrophil responses without affecting protein phosphorylation, suggest that protein phosphorylation is an insufficient signal for neutrophil activation. Inasmuch as cocaine and its derivatives affect cell functions at sites distal to activation of protein kinase C, these agents should prove useful in uncoupling protein phosphorylation from functional responses.
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PMID:Cocaine and its derivatives blunt neutrophil functions without influencing phosphorylation of a 47-kilodalton component of the reduced nicotinamide-adenine dinucleotide phosphate oxidase. 216 79

By studying the effects of whole-body X irradiation on phagocytosis, a correlation between the metabolic and bactericidal activities of leukocytes following X irradiation was demonstrated. The total nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) content of polymorphonuclear neutrolphils (PMN) isolated from irradiated guinea pigs increased significantly when compared to nonirradiated controls. The ratio of unreduced to reduced (NAD) generally increased in PMN isolated from irradiated animals. This occurred with both resting and phagocytizing cells. The ratio of unreduced to reduced NADP of resting PMN isolated from irradiated animals had a tendency to increase. However, in phagocytizing cells a significant decrease in the ratio was noted. The total acid and alkaline phosphatase and beta-glucuronidase increased up to about 10 days postirradiation. These lysosomal enzymes returned to approximately normal by the 17th day postirradiation. All three lysosomal enzymes (acid and alkaline phosphatases and beta-glucuronidase) were released from the granules at a significantly faster rate during phagocytosis after irradiation. The bactericidal activities of PMN isolated from irradiated animals gradually decreased, and in some cases increased growth of the organisms was observed. The uptake or association of bacteria with PMN isolated from irradiated animals varied with the postirradiation time. Generally, a correlation with bactericidal activities could be made. The data indicate that the bactericidal system in phagocytes consists of at least two agents, H(2)O(2) and myeloperoxidase.
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PMID:Role of the phagocyte in host-parasite interactions. 8. Effect of whole-body x-irradiation on nicotinamides, lysosomal enzymes and bactericidal activities of leukocytes during phagocytosis. 438 85

Toxicity tests on Culex pipiens fatigans with propoxur (o-isopropoxyphenyl methylcarbamate) and carbofuran (2,2-dimethyl-2,3-dihydrobenzofuranyl-7-methylcarbamate) indicated that both compounds are fast-acting insecticides. Transfer of treated larvae to fresh water results in their partial recovery from knockdown.Propoxur is metabolized by resistant and susceptible larvae by their homogenate-reduced nicotinamide-adenine dinucleotide phosphate (NADPH(2)) enzyme system and by the microsome-plus-soluble fraction of mouse-liver extracts to at least 10 organosoluble metabolites with the isopropoxy group intact. The major metabolites, which are primarily hydroxylation products or the result of degradation of these products, have tentatively been identified as: acetone plus o-hydroxyphenyl methylcarbamate, 2-isopropoxy-5-hydroxyphenyl methylcarbamate, 2-isopropoxyphenyl carbamate, and 2-isopropoxyphenyl N-hydroxymethylcarbamate. Upon incubation of water-soluble products from treated larvae with beta-glucosidase, beta-glucuronidase, aryl sulfatase and acid phosphatase, the conjugates are hydrolysed, liberating mainly hydroxylated carbamates.The results indicate that slower absorption as well as faster detoxification by hydroxylation mechanisms, together with conjugation with polar molecules and elimination, are major factors in resistance of mosquito larvae to substituted-aryl methylcarbamate insecticides.
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PMID:Carbamate resistance in mosquitos. The metabolism of propoxur by susceptible and resistant larvae of Culex pipiens fatigans. 531 55

Tendon tissue of eleven athletes suffering from insertion tendopathy and of two controls was examined. Part of the tissue was prepared for routine light microscopy, a part for enzyme histochemical staining of Nicotinamide-adenine-dinudeotide-diaphorase (NADP-diaphorase), lactate dehydrogenase (LDH), beta-glucuronidase and alkaline phosphatase. Small pieces of tissue were also prepared for electron microscopic examination. The removed tissue was edematous and mushy. The normally densely packed parallel or interwoven collagen bundles were loosened by edema, focal necrosis or hemorrhage. Infiltration of fatty tissue and granulation tissue was also present. The amount of acid mucopolysaccharides was markedly increased. The histochemical studies showed strong enzyme activity of NADP-diaphorase and LDH in normal tendon tissue as well as around areas of degeneration and in granulation tissue. beta-Glucuronidase and alkaline phosphatase was present, but in general with lesser activity than the above enzymes. The electron microscopic examination revealed marked degeneration of the fiber systems, focal necrosis, deposit of amorphous masses and mucopolysaccharides and focal mineralisation. The reparative zones showed proliferating capillaries, often with a collapsed lumen and prominent endothelial cells and basement membranes.
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PMID:Insertion tendopathy in athletes. A light microscopic, histochemical and electron microscopic examination. 712 23

Numerous, highly conserved RING-H2 domains are found in the model plant Arabidopsis thaliana (thale cress). To characterize potential RING-H2 protein interactions, the small RING-H2 protein RHA2a was used as bait in a yeast two-hybrid screen. RHA2a interacted with one of the plant-specific NAC [NAM ('no apical meristem'), ATAF1/2, CUC2 ('cup-shaped cotyledons 2')] transcription factors, here named ANAC (abscisic acid-responsive NAC). The core RING-H2 domain was sufficient for the interaction. The ability of 11 structurally diverse RING-H2 domains to interact with ANAC was then examined. Robust interaction was detected for three of the domains, suggesting multi-specificity for the interaction. The domains that interacted with ANAC contain a glutamic acid residue in a position corresponding to a proline in many RING-H2 domains. Conversion of this glutamic acid residue into proline in RHA2a decreased its ability to interact with ANAC, most likely by changing the interaction surface. This suggested that a short, divergent region in RING-H2 domains modulate interaction specificity. ANAC contains a degenerate bipartite nuclear localization signal (NLS), while RHG1a, also identified as an ANAC interaction partner, contains a basic NLS. Both signals localized beta-glucuronidase reporter fusions to the nucleus. N-terminally truncated RHA2a also directed nuclear localization, apparently dependent on basic amino acids in the RING-H2 domain. Nuclear co-localization of the RING-H2 proteins and ANAC may enable their interaction in vivo to regulate the activity of the ANAC transcription factor.
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PMID:Interactions between plant RING-H2 and plant-specific NAC (NAM/ATAF1/2/CUC2) proteins: RING-H2 molecular specificity and cellular localization. 1264 39