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

Ovulated opossum oocytes are surrounded by a zona pellucida, but not by cumulus cells. Opossum sperm carry at least four acrosomal hydrolases (hyaluronidase, acrosin, N-acetylhexosaminidase, and arylsulfatase); the functions of these enzymes in opossum fertilization are uncertain. To identify possible substrates for these hydrolases, the ultrastructure of opossum oocytes was examined after fixation in the presence of ruthenium red which stabilizes extracellular matrices. This oocyte is unusual in having a wide perivitelline space containing a highly structured extracellular matrix (ECM). The ECM is comprised of granules and filaments, and it resembles matrices known to contain hyaluronic acid in other systems. Hydrolases, known to be present in opossum acrosomes, were tested for their effect on the ultrastructure of the zona pellucida and matrix of the perivitelline space. Trypsin dissolved the zona pellucida and decreased the size of the granules in the perivitelline space. Streptomyces hyaluronidase, which specifically attacks hyaluronic acid, removed only matrix filaments. Arylsulfatase, N-acetylhexosaminidase, and beta-glucuronidase did not affect the zona pellucida or ECM in our assay. These observations are consistent with the ideas that (1) opossum sperm must penetrate two oocyte investments, the zona pellucida and ECM of the perivitelline space; (2) the ECM contains hyaluronic acid (filaments) and protein (granules); (3) opossum sperm acrosin may function in penetration of the zona pellucida and ECM; and (4) opossum sperm hyaluronidase may function in penetration of the ECM by degrading hyaluronic acid (filaments). Dissolution of the granules and filaments from oocyte microvilli is probably necessary to permit close apposition and fusion of the sperm and oocyte membranes. The evolutionary significance of these results is discussed.
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PMID:Ultrastructure of opossum oocyte investing coats and their sensitivity to trypsin and hyaluronidase. 671 16

We have isolated from monkey (Macaca radiata) brain lysosomal fraction by phosphomannan-Sepharose chromatography a protein that binds four different lysosomal enzymes, beta-hexosaminidase, beta-glucuronidase, alpha-L-fucosidase and arylsulfatase. The isolated protein which appeared in an aggregated homogeneous form on gel electrophoresis under non-denaturing conditions at both pH 8.3 and pH 5.0 was found to be heterogeneous on SDS-gel electrophoresis with molecular weights less than 67,000. Binding was partly abolished by periodate treatment or by alkaline phosphatase treatment of the lysosomal enzymes. Binding was completely abolished by pronase digestion of the binding protein. Of the different sugars tested for inhibition of binding, mannose-6-phosphate was most effective followed by mannose and N-acetyl glucosamine while glucose and fucose were ineffective.
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PMID:A binding protein for lysosomal enzymes isolated from brain by phosphomannan-sepharose chromatography. 684 56

In bile specimens from postoperative patients with biliary drainage following cholecystectomy, in addition to unchanged dibromosulfophthalein (DBSP), a single polar metabolite of DBSP was found after i.v. injection of 5 mg/kg of the diagnostic dye. This metabolite, which has not previously been detected, was resistant to beta-glucuronidase and arylsulfatase and was remarkably stable in strongly acid and alkaline solutions. It exhibited the same spectrum and colour change interval as unchanged DBSP. Further studies of its identity revealed that it gave a ninhydrin-positive reaction and that its Rf-value on TLC could be restored by Raney-nickel reduction. Amino-acid analysis after reduction and acid hydrolysis showed an increase in glutamic acid and alanine that can be considered as splitting products of conjugated glutathione following these procedures. Estimation of the quantity of this possible glutathione conjugate indicates that it is formed less rapidly than the glutathione derivative of the tetrabromoanalogue BSP, and that it represents up to 25% of the total dye excreted in bile. The observed metabolism of DBSP in man may complicate its use in the study of hepatic transport function, and negates the previous assumption that, as in certain other animal species, the dye is excreted unchanged.
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PMID:Formation of a metabolite of dibromosulfophthalein (DBSP) in man. 687 53

Iduronate sulfatase was purified from human liver for an investigation of the degradative pathway of dermatan sulfate. An overall 80-fold purification was achieved and, more importantly, the preparation was free of alpha-L-iduronidase, beta-glucuronidase, N-acetylgalactosamine 4-sulfate sulfatase (arylsulfatase B) and highly enriched in beta-N-acetylhexosaminidase. The liver enzyme appeared to be composed of several molecular species. The enzyme activity was optimal at pH 4.0 and its Km was 10--20 microM with sulfoiduronyl sulfoanhydromannitol. Chloride was inhibitory at high concentration and among divalent metal ions, only copper was inhibitory. Nitrocatechol sulfate was not a substrate, but did show competitive inhibition. Its Ki for iduronate sulfatase was similar to its Km for arylsulfatase, suggesting a similarity in the substrate binding sites of iduronate sulfatase and arylsulfatases.
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PMID:Purification and some properties of human liver iduronate sulfatase. 695 Sep 34

beta-Hexosaminidase, beta-glucuronidase, arylsulfatase, and tryptase were each released along with histamine from dispersed purified human lung mast cells of 40 to 80% purity by rabbit IgG anti-human IgE. The net per cent release ratio of each enzyme to histamine was determined over all doses of antibody employed to activate the mast cells and over all time points after activation, and indicated the per cent of each enzyme stored in secretory granules along with histamine. By multiplying the net per cent release ratio of each enzyme to histamine by total enzyme content in a preparation of 10(6) mast cells, values for secretory granule content per 10(6) mast cells were found to be 3.8 U for beta-hexosaminidase, 0.03 U for beta-glucuronidase, 0.03 U for arylsulfatase, and 0.9 U for tryptase. Subtype analysis of beta-hexosaminidase by diethylaminoethyl- (DEAE) cellulose chromatography revealed that the B isomer predominates in human mast cell secretory granules, whereas the A isomer predominates in secretory granules of the rat mast cell. Tryptase, the predominant neutral protease of the human mast cell secretory granule, has a m.w. of 130,000 by gel filtration chromatography, whereas the major neutral protease of the rat mast cell is chymotryptic and of 25,000 m.w. The presence of acid hydrolases, a tryptase, and histamine in human mast cell secretory granules suggests that the activated mast cell plays a direct role in the production of acute and subacute inflammation.
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PMID:Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells. 700 36

Phenacetin was mutagenic in Salmonella typhimurium TA100 in plate assays when liver fractions from Aroclor-treated hamsters, but not rats, were used. Its known or putative metabolites were synthesized; of these, N-hydroxyphenacetin and N-acetoxyphenacetin were found to be mutagenic in liquid and plate assays, both requiring activation by liver fractions from Aroclor-treated hamsters. 2-Hydroxyphenacetin and 2-acetoxyphenacetin were nonmutagenic. N-Hydroxyphenetidine (the deacetylated metabolite of phenacetin) and p-nitrosophenetole were the only products that were found to be mutagenic per se when assayed under N2 in either Salmonella TA100 and TA100 NR (nitroreductase-deficient) strains. Phenacetin was administered to male BDVI rats and Syrian golden hamsters, and its urinary metabolites were deconjugated with beta-glucuronidase:arylsulfatase. After reactivation by hamsters liver fractions, mutagenicity was demonstrated in S. typhimurium TA100 with urine from phenacetin-treated hamsters, but not with that from rats. After treatment with deconjugating enzymes, N-hydroxyphenacetin was isolated from hamster urine by high-performance liquid chromatography and identified by mass spectral analysis. The data support the conclusions that (a) N-hydroxyphenacetin is a proximate mutagenic metabolite of phenacetin which, after N-deacylation, is responsible for the mutagenicity observed in vitro and in the urine of hamsters and (b) the higher yield of N-hydroxyphenacetin that is formed in the liver of hamsters as compared to rats explains the pronounced species-specific activation of phenacetin into bacterial mutagens.
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PMID:Species-specific activation of phenacetin into bacterial mutagens by hamster liver enzymes and identification of N-hydroxyphenacetin O-glucuronide as a promutagen in the urine. 704 20

Cunninghamella elegans oxidized naphthalene to ethyl acetate-soluble and water-soluble metabolites. Experiments with [14C]-naphthalene indicated that 21% of the substrate was converted into metabolites. The ratio of organic-soluble metabolites to water-soluble metabolites was 76:24. The major ethyl acetate-soluble naphthalene metabolites were trans-1,2-dihydroxy-1,2-dihydro-naphthalene, 4-hydroxy-1-tetralone, and 1-naphthol. Enzymatic treatment of the aqueous phase with either arylsulfatase or beta-glucuronidase released metabolites of naphthalene that were extractable with ethyl acetate. In both cases, the major metabolite was 1-naphthol. The ratio of water-soluble sulfate conjugates to water-soluble glucuronide conjugates was 1:1. Direct analysis of the aqueous phase by high-pressure liquid and thin-layer chromatographic and mass spectrometric techniques indicated that 1-naphthyl sulfate and 1-naphthyl glucuronic acid were major water-soluble metabolites formed from the fungal metabolism of naphthalene. C. elegans oxidized biphenyl primarily to 4-hydroxy biphenyl. Deconjugation experiments with biphenyl water-soluble metabolites indicated that the glucuronide and sulfate ester of 4-hydroxy biphenyl were metabolites. The data demonstrate that sulfation and glucuronidation are major pathways in the metabolism of aromatic hydrocarbons by fungi.
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PMID:Glucuronide and sulfate conjugation in the fungal metabolism of aromatic hydrocarbons. 710 74

A method was developed for the hydrolysis of conjugated iodothyronines in bile with the aid of beta-glucuronidase/arylsulfatase and for subsequent direct estimation of total and free iodothyronines with the aid of specific radioimmunoassay. The amount of conjugated fraction could then be calculated from the difference. Thus, basal biliary excretion of several iodothyronines was measured in 31 normal, fed rats in which the bile duct was drained with polyethylene tubing under pentobarbiturate anesthesia and the bile was collected for 2 h. The free fraction of thyroxine, 3,5,3'-triiodothyronine and 3,3'-diiodothyronine was approx. 30% of total content, while that of 3,3',5'-triiodothyronine and 3,5-diiodothyronine was approx. 20% and that of 3',5'-diiodothyronine was less than 10%. This suggests some considerable differences in the conjugation of individual iodothyronines in the liver. The concentration of T4 in bile was about the same as in plasma, while that of other iodothyronines was about 3-8 times higher than in plasma. This shows close interrelations between the iodothyronine deiodinating pathway in liver cells in vivo and the spectrum of iodothyronine in bile. The average ratio of T3/rT3 as found in bile was about 4.
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PMID:Direct quantitative estimation of several iodothyronines in rat bile by radioimmunoassay and basal data on their biliary excretion. 711 59

Following p.o. administration of 14C-labelled rac.-1-(e)-(m-methoxyphenyl)-2-(e)-dimethylaminomethyl-cyclohexan-1-(a)-ol hydrochloride (tramadol hydrochloride, CG 315, Tramal) to mice, hamsters, rats, guinea pigs, rabbits, dogs and man the metabolic pathways were investigated and the results compared. After synthesis of the reference substances the metabolites were identified by co-chromatography using both TLC (thin-layer chromatography) and HPLC (high-performance liquid chromatography) methods, by co-crystallization and by gas chromatography-mass spectrometry. In all species the main metabolic pathways are N- and O-demethylation (phase I reactions) and conjugation of O-demethylated compounds (phase II reactions). 11 metabolites are known, 5 arising by phase I reactions (M1 to M5) and 6 by phase II reactions (glucuronides and sulfates of M1, M4 and M5). The 5 phase I metabolites are mono-O-demethyl-tramadol (M1), mono-N-demethyl-tramadol (M2), di-N-demethyl-tramadol (M3), tri-N,O-demethyl-tramadol (M4) and di-N,O-demethyl-tramadol (M5). The biotransformation scheme of tramadol is qualitatively identical in man, dog, rabbit, guinea pig, rat, hamster and mouse. In all species M1 and M1-conjugates, M5 and M5-conjugates and M2 are the main metabolites, whereas M3, M4 and M4-conjugates were only formed in minor quantities. Following p.o. administration to man and animals 14C-tramadol are rapidly and almost completely absorbed. The unchanged drug and metabolites are mainly excreted via kidneys. The cumulative renal excretion of total radioactivity accounts for approximately 90% in man and varies from 86 to 100% in mouse, hamster, rat, guinea pig, rabbit and dog; the residual of the applied radioactivity appears in the feces. Apparently tramadol is metabolized much more rapidly in animals than in man. For that reason there are appreciable differences between man and animals in the amount of tramadol excreted unchanged in the urine (about 30% and 1% of the p.o. dose, respectively). After incubation with beta-glucuronidase and arylsulfatase at least 81% of the excreted radioactivity could be extracted from the urine of man animals (with the exception of the guinea pig and the rabbit). In man all extractable metabolites were identified.
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PMID:[Biotransformation of tramadol in man and animal (author's transl)]. 719 74

Severance of the anterior cruciate ligament in the knees of mature beagles caused instability and resulted in the slow onset of changes comparable to those present in human osteoarthritis (OA). Heightened cellular activities were reflected in increased levels of arylsulfatase, acid phosphatase, and beta-glucuronidase in the articular cartilage. Similar increases in these lysosomal enzyme activities were found in the synovial fluid of the operated joints. Dietary supplementation with vitamin C resulted in increased serum protein content and increased cartilage formation, although ascorbate had no effect on enzyme activities. The early stages of OA in mature beagles, therefore, were characterized by interference with normal chondrocyte metabolism which resulted in staggered elevation of different lysosomal enzymes.
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PMID:Metabolic response during early stages of surgically-induced osteoarthritis in mature beagles. 720 21


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