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:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A radiochemical method for the studies on the microsomal UDPglucuronic acid metabolism has been developed. 2. The rat liver microsomes caused a rapid hydrolysis of UDPglucuronic acid to D-glucuronic acid 1-phosphate and further although much slower to free D-glucuronic acid. In Tris-HCl buffer (pH 7.4) they were produced in ratio 72 : 1. No other metabolites were found in measurable amounts. The pyrophosphatase splitting UDPglucuronic acid showed a pH optimum at 8.9, but the liberation of D-glucuronic acid from UDPglucuronic acid had two pH maxima (pH 3.5 and 8.5). EDTA appeared to be less powerful inhibitor of pyrophosphatase than previously suggested. About 25 per cent of the UDPglucuronic acid hydrolyzing activity was still remaining in the presence of 10 mM EDTA. D-Glucaro-1,4-lactone was found to have a slight inhibitory action on the pyrophosphatase activity. Citrate inhibited powerfully the hydrolysis of UDPglucuronic acid and the liberation of free D-glucuronic acid. Phosphate was also inhibitory. 3. In the presence of an exogenous UDPglucuronosyltransferase substrate, 4-nitrophenol, the formation of D-glucuronic acid 1-phosphate and free D-glucuronic acid were slightly reduced, and D-glucuronic acid 1-phosphate, 4-nitrophenylglucuronide and free D-glucuronic acid were produced in ratio 78 : 23 : 1. When 10 mM EDTA was added to diminish the hydrolytic consumption of the glucuronyl donor substrate, the corresponding ratio was still as unfavorable as 19 : 2.6 : 1. The measurable activity of UDPglucuronosyltransferase was lower in the presence of phosphate or citrate than in Tris-HCl buffer, although they protected the glucuronyl donor substrate against hydrolysis. 4. The results indicate that even in the presence of added glucuronyl acceptor substrate the hydrolysis of UDPglucuronic acid predominates the conjugation in rat liver microsomes. The rate of the hydrolysis of UDPglucuronic acid is quite considerable even in the presence of EDTA, and it is recommended to control the UDPglucuronic acid pyrophosphatase activity when UDPglucuronosyltransferase and glucuronidation reactions are studied. Free D-glucuronic acid appears to be produced from UDPglucuronic acid for further use via D-glucuronic acid 1-phosphate, the rate-limiting step being the hydrolysis of this intermediate. UDP-glucuronosyltransferase, glucuronides of either endogenous or exogenous aglycones and beta-glucuronidase have only a minor role in this respect in rat liver microsomes.
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PMID:Pyrophosphatase and glucuronosyltransferase in microsomal UDPglucuronic-acid metabolism in the rat liver. 0 Dec 76

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

The effects of dexamethasone sodium phosphate (DSP), 5 mg/kg, administration on the biochemical alterations in hepatic tissue subsequent to the production os splanchnic artery occlusion (SAO) shock was investigated. Following the induction of SAO shock, DSP-treated dogs exhibited a significantly improved cardiovascular status compared to placebo-treated shocked dogs, 2 hr after release of the occlusion, biopsies of the liver were taken and analyzed for beta-glucuronidase (BG), adenosine-3',5'-cyclic monophosphate (cAMP) and guanosine-3',5'-cyclic monophosphate (cGMP) content. SAO shock produced a significant increase in hepatic free BG activity which was reversed by DSP pretreatment. Additionally, SAO shock decreased hepatic cAMP levels, increased cGMP levels and significantly lowered the hepatic ratio of cAMP/cGMP. These changes in cyclic nucleotide levels were reversed by DSP administration and were found to be inversely related to changes in hepatic free BG activity. Thus, the ratio of cellular cAMP/cGMP may function as a regulatory mechanism for lysosomal enzyme release secondary to ischemia and hypoxia. Further, DSP may act to maintain lysosomal integrity in ischemic tissues by preservation of cAMP/cGMP ratios.
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PMID:Alterations in splanchnic cyclic nucleotide levels in splanchnic artery occlusion shock and their modification by dexamethasone. 17 27

The effect of N6,O2'-dibutyryl adenosine 3',5'-cyclic-monophosphate (dbcAMP) on the mobilization of calcium (Ca2+), inorganic phosphate (Pi) and lysosomal enzymes was studied in a bone culture system for 24 h using half calvaria from 6--7 day-old mice. DbcAMP inhibited spontaneous as well as parathyroid hormone-stimulated mineral mobilization. DbcAMP in a concentration of 5 x 10(-4)M also reduced the activities of beta-glucuronidase, beta-galactosidase and acid phosphatase found in the media while the activities of lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase were not affected. It is concluded that cAMP is not a stimulator but an inhibitor of bone resorption within the culture period studied (24 h) and that the cyclic nucleotide might interfere with release processes involved in bone resorption.
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PMID:Inhibitory effect of dibutyryl cyclic AMP on the release of calcium, inorganic phosphate and lysosomal enzymes from calvarial bones cultured for 24 hours. 22 6

Human platelet plasma membranes were isolated with polylysine beads according to the technique developed by Jacobson and Branton (1977, Science [Wash. D. C.] 195:302--304). Lactoperoxidase-catalyzed surface iodination revealed that ninefold greater 125I specific activity was associated with the membranes isolated on beads than with whole platelets. Enrichment in the bead membrane preparation of the activities of membrane marker enzymes, bis(p-nitrophenyl)phosphate phosphodiesterase and Na,K-ATPase, was 8.0 and 4.4, respectively. Contamination with enzymes of other organelles, cytochrome oxidase and beta-glucuronidase, was relatively low as compared with membranes isolated by sucrose gradient centrifugation. Analysis by SDS polyacrylamide gel electrophoresis showed that a full complement of surface glycoproteins was present on the membranes isolated with polylysine beads. The polylysine bead technique is a rapid, reproducible and efficient method for the preparation of relatively pure platelet plasma membranes.
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PMID:Isolation of human platelet plasma membranes with polylysine beads. 22 8

Human beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase, EC 3.2.1.31), like many other glycoprotein lysosomal hydrolases, is specifically taken up from the culture medium by human fibroblasts. Prior work has indicated that the enzyme exhibits charge heterogeneity and that "high-uptake" forms, i.e., those rapidly internalized by human fibroblasts, are more acidic than slowly internalized forms. Here we present two lines of evidence that the acidic group required for the high-uptake property of certain forms of the enzyme is a phosphate on, or in proximity to, a D-mannose-type carbohydrate. The first line of evidence was obtained from analysis of inhibition of enzyme pinocytosis by yeast mannans, phosphorylated sugars, and sugars. Mannans that contained phosphate were more potent inhibitors than those that did not contain phosphate. D-Mannose 6-phosphate was a more potent inhibitor than either D-mannose 1 phosphate or 2-deoxy-D-glucose 6-phosphate. D-Mannose and certain related sugars were weak pinocytosis inhibitors, while 2- and 4-epimers of mannose were noninhibitory. Competitive inhibition was demonstrated and the apparent Kis estimated for the following compounds: Saccharomyces cerevisiae mannan from mutant X2180-mnnl, 3 X 10(-6) M; mannan from wild-type S. cerebisiae, 3 X 10(-5) M; D-mannose 6-phosphate, 6 X 10(-5) M; L-fucose, 4 X 10(-2) M; and D-mannose, 6 X 10(-2) M. The second line of evidence comes from the observation that alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] treatment of human platelet beta-glucuronidase abolished its "high-uptake" activity, without diminishing its catalytic activity, and converted some forms of the heterogeneous enzyme to less acidic forms.
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PMID:Phosphohexosyl components of a lysosomal enzyme are recognized by pinocytosis receptors on human fibroblasts. 26 21

Human beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase, EC 3.2.1.31), like many other glycoprotein lysosomal hydrolases, is subject to receptor-mediated endocytosis by fibroblasts. Prior work demonstrated charge heterogeneity in beta-glucuronidase and showed that high-uptake forms are more acidic than slowly internalized forms. Considerable indirect evidence implicated mannose 6-phosphate as an essential part of the recognition marker on high-uptake enzyme forms. Here we report the purification of beta-glucuronidase from human spleen and demonstrate enzymatically that mannose 6-phosphate is released on acid hydrolysis of pure enzyme varies directly with its susceptibility to pinocytosis by fibroblasts. Enzyme forms resolved by CM-Sephadex chromatography differed over an 18-fold range in uptake rate and in mannose 6-phosphate content. The most acidic forms had 4.4 mol of mannose 6-phosphate per mol of enzyme. The mannose 6-phosphate was released from the enzyme by treatment with endoglycosidase H with concomitant loss of susceptibility to adsorptive endocytosis. Thus, these studies provide direct evidence that mannose 6-phosphate is present on high-uptake enzyme forms, that it is present in the recognition marker for uptake, and that it is present on oligosaccharide that is released by endoglycosidase H.
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PMID:Enzymatic identification of mannose 6-phosphate on the recognition marker for receptor-mediated pinocytosis of beta-glucuronidase by human fibroblasts. 29 66

1. Hemolymph from the giant African snail Archachatina marginata has been analyzed for its content of certain lysosomal hydrolases and shown to contain substantial quantities of acid phosphatase (285 units/ml) hexosaminidase (512 units per ml) and beta-glucuronidase (28 units/ml). 2. Hemolymph acid phosphatase can be fractionated into 6 active components by DEAE-Sephadex chromatography. 3. Some of the acid phosphatase species can be distinguished on the basis of heat stability, pH dependency and sensitivity to inhibitors including phosphate, L(+) tartrate, fluoride, formaldehyde and 1.10 phenanthroline.
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PMID:Demonstration of multiple forms of acid phosphatase in hemolymph of the African snail, Archachatina marginata. 31 14

Pigment gallstones are defined as any dark brown-to-black stone, consisting of calcium salts of bilirubin, phosphate, carbonate and other anions, and can be separated into carbonate- and noncarbonate-containing groups. Pigment stones predominate in the rural Orient, in cirrhosis, and in elderly United States patients undergoing cholecystectomy. Clinical associations include bile duct obstruction, stasis, and possibly hemolysis. Of pigment stones, 50% are radioopaque and account for two-thirds of all opaque stones. The concentrations of bile salts, phospholipids,, cholesterol, and total bilirubin in bile are similar to normal levels, but the concentration of unconjugated bilirubin is increased in the bile of some patients. Increased unconjugated bilirubin in bile may be caused by increased hydrolysis of excreted conjugated bilirubin. Unconjugated bilirubin is solubilized by bile salts, but the interaction is primarily nonmicellar. Ionized calcium and pH are important determinants of solubility. Sulfated glycoproteins, excreted in increased amounts in patients with cholelithiasis, may be the site of pigment stone precipitation because these compounds bind calcium salts tightly. E coli is frequently cultured from pigment stones in Japan but not in the United States; thus, bacterial beta-glucuronidase may be important in stone formation in Japan but probably not in the West. Stasis leads to increased calcium secretion and to increases in the concentration of sparingly soluble compounds that may then precipitate. Incomplete emptying of the gallbladder may result in the same concentration process. Unsaturated fats and chronic vagal stimulation cause pigment stone formation in animals. At present, surgery is the only treatment for pigment lithiasis.
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PMID:Pigment gallstones. 31 81

Histoenzymatic changes in cells of the reticulo-endothelial system of liver and spleen and in hepatocytes were studied in the course of acute poisoning with Morfamquat dichloride, without and under the screen of vitamin E (to mice tissue restrictive respiration compound). This herbicide was given to mice in single, intraperitoneal injection of 100 mg/kg b.w. The choice of the enzymes was based on the so-called markers of the lysosomes structures of a cell (acid phosphatase-APh-EC. 3.1.3.2. and beta-glucuronidase-beta-GU-EC. 3.2.1.31) and Golgi apparatus (thiamin pyrophosphatase-TPP-EC. 3.5.99.2) It was stated that Morfamquat dichloride caused clear stimulation in the reticuloendothelial system of the organism, with occurrence of the high activity of APh and beta-GU in the lysosome and phagolysosome structures, growth of the lysosome membranes permeability and passing their content to cytoplasm. Furthermore, the increased activity of TPP-ase in Golgi apparatus hepatocytes of animals liver may point to disturbances of the pirogroniam decarboxylation and also to disturbances of the pentose-phosphate cycle. The application of vitamin E to mice for 5 days before the poisoning, protects animals distinctly against the toxic activity of the herbicide.
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PMID:[Histoenzymatic reactions in the cells of the reticuloendothelial system of the liver and spleen and hepatocytes in acute Morfamquat dichloride poisoning]. 55 86


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