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)

Water-soluble aflatoxin conjugates prepared from urine samples from rats, mice and rhesus monkeys dosed with [14C]aflatoxin B1 (AFB1) ip or iv were hydrolysed by enzymes (beta-glucuronidase and sulphatase), acid or a combination of both treatments. Different amounts of AFB1 and its metabolites were found in hydrolysates from different sources, indicating the presence of glucuronide, sulphate and possibly mercapturate conjugates of aflatoxins. In addition to aflatoxins M1, P1, Q1 and B2a, AFB1 was frequently identified in the products released from the hydrolysates. These water-soluble aflatoxin conjugates were not mutagenic to Salmonella typhimurium TA98 in the presence of rat-liver S-9 mix. However, chloroform extracts of the hydrolysates from beta-glucuronidase and sulphatase treatment showed mutagenic activity in these bacteria in the presence of S-9 mix. Although very low levels of AFB1 radioactivity were detected in the hydrolysates, the potent mutagenic activity of AFB1 contributed to the high numbers of revertant colonies. AFP1 was detected in urine samples from monkeys that were pretreated with phenobarbital before an iv dose of AFB1. No mutagenic activity was detected in the enzymatic hydrolysate of the sample from these monkeys. The results thus indicate that AFB1 can form glucuronide and/or sulphate conjugate(s) directly and be excreted in the urine.
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PMID:Characterization of water-soluble glucuronide and sulphate conjugates of aflatoxin B1. 1. Urinary excretion in monkey, rat and mouse. 393 Mar 55

Aflatoxin B1 and some of its metabolites were released from water-soluble aflatoxin conjugates isolated from rat primary hepatocyte cultures and hydrolysed by enzymes (beta-glucuronidase and sulphatase), by acid or by a combination of both treatments. The presence of AFB1 in the hydrolysates was detected on TLC plates, or indicated indirectly by the Ames mutagenicity assay. The aflatoxin conjugates were not mutagenic to Salmonella typhimurium strain TA98 in the presence of rat-liver S-9 mix. However, following enzymatic hydrolysis, the chloroform extract of the hydrolysate was highly mutagenic to the bacteria, indicating the presence of mutagenic AFB1. The conjugates AFB1-glucuronide and AFB1-sulphate are therefore produced from AFB1 in primary cultures of rat hepatocytes.
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PMID:Characterization of water-soluble glucuronide and sulphate conjugates of aflatoxin B1. 2. Studies in primary cultures of rat hepatocytes. 393 Mar 56

We have recently reported that human neutrophils can be permeabilized with the cholesterol complexing agent saponin and that these cells can be induced to secrete the granule enzyme lysozyme in response to micromolar levels of free calcium. We now report that digitonin can be used in place of saponin and that it has several advantages. Permeabilization of human neutrophils was accomplished with 10 micrograms/ml digitonin in a high potassium medium. Normally impermeant solutes such as [14C]sucrose and inulin [14C]carboxylic acid gained access to one half of the intracellular water space marked with [3H]H2O. Between 30 and 100% of the cytoplasmic enzyme, lactate dehydrogenase, leaked from the intracellular space. The permeabilization process and calcium-triggered granule secretion were critically dependent upon temperature, time and digitonin concentration. Permeabilized neutrophils secreted beta-glucuronidase, lysozyme and vitamin B-12 binding-protein, constituents of both azurophil and specific granules, when exposed to micromolar levels of free calcium. Release of specific granule constituents appeared to be more sensitive to free calcium than release from azurophil granules. Although the amount of permeabilization varied considerably with each batch of cells, release of these granule markers was a consistent finding. Release of granule markers was accompanied by resealing of the cells to high-molecular-weight (Mr greater than 5000) solutes. Electron microscopic evidence also suggested that granule and plasma membranes were intact following digitonin treatment and that fusion of these membranes occurred in response to calcium. These results suggest that elevation of intracellular free-calcium levels is a sufficient condition for lysosomal enzyme release.
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PMID:Human neutrophils permeabilized with digitonin respond with lysosomal enzyme release when exposed to micromolar levels of free calcium. 395 77

The biliary excretion of radioactivity after intravenous [3H]25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than [3H]25-hydroxyvitamin D3. No free [3H]25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following [3H]25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.
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PMID:Biliary excretion of radioactivity after intravenous administration of [3H]25-hydroxyvitamin D3 in man. 395 32

Permeabilization of human neutrophils has been accomplished by using saponin, a cholesterol complexing agent, permitting experimental manipulation of the intracellular milieu. Access of ordinarily impermeable solutes, such as [14C]-inulin or [14C]-sucrose, to the water space of the cells was considered the main criterion for permeabilization. Other criteria were substantial (50 to 80%) release of cytoplasmic lactate dehydrogenase and permeability to trypan blue. Successful permeabilization did not cause substantial release of the granule enzymes lysozyme or beta-glucuronidase. Washing the neutrophils, to remove soluble saponin and released cytoplasmic contents, and resuspension did not alter their permeabilized character. By supplementing the medium with CaCl2, thereby obtaining free Ca2+ concentrations of 1.5 X 10(-7) M to 10(-4) M, it was possible to stimulate lysozyme secretion from washed or unwashed permeabilized neutrophils. A total of 20 to 30% of the total cellular lysozyme was released during an incubation of 5 min at 37 degrees C. Secretion was inversely related to cell concentration. No beta-glucuronidase was secreted under these conditions and no response was obtained by using unpermeabilized cells. Thus, permeabilized neutrophils respond to increases in free Ca2+ alone, without resorting to conventional secretagogues. This system also permits the manipulation of intracellular constituents important for stimulus-response coupling.
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PMID:Micromolar concentrations of free calcium provoke secretion of lysozyme from human neutrophils permeabilized with saponin. 396 35

Human bile contains a considerable amount of endogenous beta-glucuronidase. The effects of pH and bile acids on its activity have been studied in regard to its role in the pathogenesis of cholelithiasis. beta-Glucuronidase, purified from human liver to homogeneity, was structurally stable between pH 4 and 10, but was active only over a much narrower range of pH, with a pH optimum of 5.2. The inactivation below pH 4 was due to its irreversible denaturation, whereas the inactivation at higher pH was due to a true reversible pH effect on the enzyme velocity. Kinetic studies revealed that hydrogen ion acted as a substrate-directed activator of the free enzyme, but not the enzyme-substrate complex, with a molecular dissociation constant of 4 X 10(-6). The enzyme activity was not affected by unconjugated bile acids, primarily due to their extremely low water solubility. Conjugated bile acids, on the other hand, exerted heterogeneous and pH-dependent effects on the enzyme. At pH 5.2, taurocholic acid and glycocholic acid were substrate-directed activators of the enzyme; taurochenodeoxycholic acid and taurodeoxycholic acid, competitive inhibitors; and glycochenodeoxycholic acid and glycodeoxycholic acid, mixed inhibitors. At pH 7.0 all taurine and glycine conjugates behaved as substrate-directed activators. Though beta-glucuronidase activity at pH 7 was only 23% of its maximal activity at pH 5.2, conjugated bile acids tended to restore its activity to a certain extent at pH 7. Thus, endogenous beta-glucuronidase could play a significant role in pigment cholelithiasis.
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PMID:Human beta-glucuronidase. Studies on the effects of pH and bile acids in regard to its role in the pathogenesis of cholelithiasis. 397 Sep 37

Four mouse hepatoma cell lines, a parent (Hepa-1c1c7) and three variants (MUL12, BPrc1, and TAOc1BPrc1) which had been derived from Hepa-1c1c7 by the fluorescence-activated cell sorter, were incubated with benzo(a)pyrene, and the metabolites were analyzed by high-pressure liquid chromatography. Among these four cell lines, Hepa-1c1c7 and MUL12 metabolized benzo(a)pyrene the most quickly and to the greatest extent, and BPrc1 had the weakest metabolic activity for this substrate. TAOc1BPrc1 had intermediate benzo(a)pyrene-metabolizing activity, depending on cell density and incubation time. At low cell density, the active variant TAOc1Bprc1 resembled the weakly active Bprc1 in accumulating a low amount of ethyl acetate-soluble metabolites in the medium while, at high cell density, TAOc1Bprc1 resembled the parent clone Hepa-1c1c7 and the highly active variant MUL12. At short incubation times, TAOc1Bprc1 also had low conjugating activity while, at longer incubation times, the conjugating activity approached that of Hepa-1c1c7 and MUL12. At low cell density, Bprc1 was able to produce phenols, but this variant did not seem to have this ability at high cell density. When the substrate concentration was 4 microM and the incubation time was 24 h, beta-glucuronidase treatment of water-soluble metabolites released about 5.3 times more pmol of quinones compared with phenols. But when the substrate concentration was 25 nM, beta-glucuronidase released about 2.0 times as many phenols compared with quinones. The parent and the two more actively metabolizing variants showed differences in the peak times of accumulation of 9,10-diol and 7,8-diol of benzo(a)pyrene, which may have implications for binding to DNA and nuclear proteins. It was concluded that BPrc1 has basal but not easily inducible aryl hydrocarbon hydroxylase activity, whereas Hepa-1c1c7, MUL12, and TAOc1Bprc1 have basal and inducible aryl hydrocarbon hydroxylase activity. These results show that variants of a single parent cell line can exhibit significant differences in the rate and extent of metabolism of benzo(a)pyrene.
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PMID:Metabolism of benzo(a)pyrene by variant mouse hepatoma cells. 401 32

Chromatography of benzo[a]pyrene (BaP) sulfate, glucuronide and glutathione (GSH) conjugate standards were examined by h.p.l.c. on a C8 column as modified by various organic acids and solvents. Sulfate and glucuronide standards were positional isomers derived from BaP-1,3,6,7,9 phenols and BaP-GSH conjugates consisted of a racemic mixture of BaP-4,5-GSH. In the absence of acid, BaP conjugates appeared as rapidly eluting, unresolved peaks in aqueous-methanol or acetonitrile gradients or coeluted as broad peaks in a water-propanol gradient, with the exception of BaP-7-OH sulfate which eluted as a distinct symmetrical peak. Addition of acetic or trifluoroacetic (TFA) acids enhanced column retention of BaP conjugates in each solvent system. Upon acidification of mobile phases, BaP-GSH isomers were partially resolved, isomers of BaP sulfates or of BaP glucuronides coeluted, and BaP-7-OH sulfate was resolved from all conjugates. BaP-GSH conjugates were most resolved and preceded elution of other conjugates when TFA was added to mobile phases. BaP sulfates and glucuronides generally coeluted but were partially resolved at 0.1% TFA in a water-methanol gradient. Water-soluble metabolites from cultured hamster embryo fibroblasts (HEF) incubated with [3H]BaP for 24 h were chromatographed by h.p.l.c. in a water-methanol gradient with TFA. BaP glucuronides, consisting of tetraols, triols, quinones, dihydrodiols and phenols eluted as a single peak which could be removed by beta-glucuronidase treatment and organic extraction. BaP sulfates were not detected. The remaining BaP metabolites which were resistant to enzymatic hydrolysis, generally eluted prior to BaP glucuronides suggesting they constitute a family of BaP-GSH derivatives.
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PMID:H.p.l.c. of benzo[a]pyrene glucuronide, sulfate and glutathione conjugates and water-soluble metabolites from hamster embryo fibroblasts. 402 29

An ethyl anthranilate azopigment of bilirubin conjugated to beta-d-monoglucoside was isolated from dog gall-bladder bile. Glucose was cleaved from the azopigment by treatment with beta-glucosidase and beta-glucuronidase. Mild alkaline hydrolysis of the compound by sodium methoxide yielded two kinds of compounds, water-soluble and organic-soluble. The former were shown, by enzymic analysis, t.l.c., nuclear magnetic resonance, and combined g.l.c. and mass spectrometry, to contain glucose. No evidence was obtained from these data that a disaccharide was present in this fraction. The organic-soluble compounds formed during this methanolysis were shown, by t.l.c. and mass spectrometry, to be the isomeric dipyrrole azopigments of bilirubin. These findings contribute further evidence to the controversy surrounding the nature of conjugated bilirubin.
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PMID:The isolation of an azobilirubin beta-D-monoglucoside from dog gall-bladder bile. 446 61

1. Lymph was collected directly from the hind limbs of rabbits anaesthetized with pentobarbitone and from unanaesthetized rabbits before and after one hind limb was injured by immersion in water at 60 degrees C for 1 minute.2. Rabbits were treated with anti-inflammatory agents hydrocortisone or indomethacin which, in acute experiments, were infused close-arterially into the limb either at the time of the injury or 90 min later. In chronic experiments hydrocortisone was given intravenously three times a day.3. When given at the time of the injury both drugs reduced the subsequent mean increases in the lymph of the intracellular enzymes lactate dehydrogenase and glutamic pyruvate transaminase but not those of beta-glucuronidase and protein; whereas when given 90 min after the injury only the increase in lymph protein concentration was reduced.4. The results indicate that these anti-inflammatory agents probably inhibit the second phase of increase in vascular permeability which occurs after injury and in addition, reduce the leakage of intracellular protein by a non-specific effect on membrane permeability.5. The pronounced variability of the response of individual animals and the complexity of the experiments preclude the method as a suitable model for the estimation of anti-inflammatory activity.
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PMID:The effect of anti-inflammatory agents on the changes in local lymph after thermal injury. 508 39


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