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)

Uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes from dogs, rats, or humans rapidly metabolized [3H]-N-hydroxy-2-naphthylamine (N-HO-2-NA) to a water-soluble product that yielded 98% of the parent N-hydroxy amine upon treatment with beta-glucuronidase. The metabolite was identified as N-(beta-1-glucosiduronyl)-N-hydroxy-2-naphthylamine from ultraviolet, infrared, and mass spectral analyses of the glucuronide and its nitrone derivative. Incubation of N-hydroxy-1-naphthylamine (N-HO-1-NA), N-hydroxy-4-aminobiphenyl (N-HO-ABP), or the N-hydroxy derivatives of 2-aminofluorene, 4-aminoazobenzene, or N-acetyl-2-aminofluorene with uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes also yielded water-soluble products. beta-Glucuronidase treatment released 80 to 90% of the [3H]-NHO-1-NA and [3H]-N-HO-ABP conjugates as tritiated ether-extractable derivatives. N-HO-1-NA, N-HO-2-NA, and N-HO-ABP and the glucuronides of these N-hydroxy arylamines were relatively stable and nonreactive near neutral pH. At pH 5, the N-glucuronide of N-HO-2-NA and the presumed N-glucuronides of N-HO-1-NA and N-HO-ABP were rapidly hydrolyzed to the N-hydroxy arylamines that were then converted to reactive derivatives capable of binding covalently to nucleic acids. These data support the concept that arylamine bladder carcinogens are N-oxidized and N-glucuronidated in the liver and that the N-glucuronides are transported to the urinary bladder. The hydrolysis of the glucuronides to N-hydroxy arylamines and the conversion of the latter derivatives to highly reactive electrophilic arylnitrenium ions in the normally acidic urine of dogs and humans may be critical reactions for tumor induction in the urinary bladder.
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PMID:Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. 1 29

(+)--Cyanidanol, a water-soluble flavonoid, when added to cultured skin fibroblasts of a patient with I-cell disease raised the intracellular concentration of beta-galactosidase but did not affect the distribution of arylsulfatase. A, alpha-mannosidase or beta-glucuronidase. The elevated accumulation of 35SO4 by I-cell, Hunter and Maroteaux-Lamy fibroblasts was decreased by the addition of (+)--cyanidanol to the culture medium, but the degradation of previously labeled, intracellular glycosaminoglycans was not. It is concluded that (+)--cyanidanol does not produce a biochemical correction of the enzymic abnormalities existing in I-cell fibroblasts.
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PMID:The effect of (+) --cyanidanol on lysosomal enzymes of I-cell fibroblasts. 2 Jun 73

Secondary cultures of hamster embryo cells exposed to 0.5 nmol [G-3H]7,12-dimethylbenz(a)anthracene (DMBA) per ml medium metabolized more than 90% of the DMBA within 48 hr. Samples of medium were extracted with chloroform, methanol, and water. The chloroform phases contained about one-third of the DMBA metabolites; the major chloroform-extractable metabolite was 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene. Beta-glucuronidase treatment of the aqueous methanol-soluble metabolites converted almost one-half of them to chloroform-soluble metabolites, of which more than 80% were identified as phenolic derivatives of DMBA. Similar metabolite profiles were obtained by treating the medium with beta-glucuronidase before chloroform extraction. Separation of the methyl group-hydroxylated derivatives of DMBA from the phenolic derivatives was accomplished by high-pressure liquid chromatography. Small amounts of hydroxymethyl derivatives were detected only in the chloroform-extractable material, whereas DMBA phenols were the major component of the beta-glucuronidase-released mateirla. These results indicate that the major pathway of DMBA metabolism in hamster embryo cells is oxidation of the aromatic rings and not oxidation of the methyl groups.
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PMID:Formation of glucuronic acid conjugates of 7,12-dimethylbenz(a)anthracene phenols in 7,12-dimethylbenz(a)anthracene-treated hamster embryo cell cultures. 9 31

Radiolabeled diethylstilbestrol (DES) was administered to one pregnant and three normal female rhesus monkeys. One normal female chimpanzee was also included in the study. Regardless of the mode of presentation (oral versus intravenous), the urine was the principal route of excretion for each species. The urine contained no non-polar radioactivity, and Sephadex LH-20 (MeOH/EtOH-50:50) resolved the radioactivity into five fractions (A, B, C, D, E). Fractions A,B, C, and D were hydrolyzable with beta-glucuronidase, and the principal aglycones were identified with GC/MS as cis-trans DES and dienestrol. The fecal excretory products were extracted with dimethoxy methane/methanol (50:50) and the radioactivity partitioned between benzene and H2O. The polar radioactivity was resolved by LH-20 (MeOH/EtOH-50:50) into chromatographic fractions similar to the urinary conjugates. These fecal conjugates were, however, less sensitive to beta-glucuronidase hydrolysis. The primary non-polar fecal radioactivity was chromatographically similar to DES (LH-20 and HPLC) in both species, and in the rhesus monkey the principal products identified were cis-trans DES and dienestrol.
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PMID:The metabolism of diethylstilbestrol in the rhesus monkey and chimpanzee. 10 73

The formation of glutathione (GSH) conjugate in the detoxification of [1-14C]-naphthalene and [naphthyl-14C]-carbaryl was investigated using rat liver homogenate. The mercapturic acid conjugate in rats was also investigated by collection of urine after intraperitoneal injection of 14C substrates. The formation of water-soluble metabolites in vitro from naphthalene was dependent on the amount of glutathione added, but this was not seen in carbaryl metabolism. In vitro, the metabolism of [1-14C]-naphthalene produced 50% GSH conjugates in the incubation mixture, whereas in vivo the metabolism of this compound produced 65% mercapturic acid conjugate in the urine. There was no evidence of GSH or mercapturic acid conjugate in the metabolism of [naphthyl-14C]-carbaryl in vitro and in vivo. This conclusion was made by comparing the nature and chemical characteristics of GSH and mercapturic acid conjugates formed in [1-14C]-naphthalene metabolism. With the aid of the specific enzyme (e.g. beta-glucuronidase and sulfatase) and acid hydrolysis, the water-soluble metabolites of [naphthyl-14C]-carbaryl were tentatively recognized as glucuronide or sulfate conjugated mainly with 5,6-dihydro-5,6-dihydroxycarbaryl or N-hydroxy-methyl carbaryl and their hydrolytic products. This data demonstrated that the substituent group on the naphthalene molecule may affect the significance of GSH conjugation.
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PMID:Glutathione and mercapturic acid conjugations in the metabolism of naphthalene and 1-naphthyl N-methylcarbamate (carbaryl). 12 Feb 42

The total activity per microgram of protein of alpha-arylsulphatase and beta-glucuronidase lysosomial enzymes has been determined in 20 cases of benign and malignant breast tumour. The activity of lysosomial enzymes of the normal breast tissue was always much lower than in neoplastic tissues. The difference is already fairly marked in the case of benign tumours and cystic fibroadenosis, but reaches its peak in malignant tumours where activity is 4-5 times higher than normal values. In the case of total activity, the reference is to one ml of homogenate in distilled water, and in the case of specific activity to mg of protein of the homogenate, in either case the findings are highly significant. Although these researches are at a preliminary stage, they confirm the importance of lysosomial enzyme modifications in the phenomenon of neoplastic growth in the breast.
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PMID:[Activity of lysosomal alpha-arylsulfatase and beta-glucuronidase enzymes in benign and malignant breast tumors]. 13 11

The object of this investigation was to determine whether the pathological events which occur during the Arthus and mixed hypersensitivity reaction could be monitored biochemically and whether changes in enzyme concentrations would reflect the severity of tissue damage either in the skin itself or in the lymph draining the lesion. The initial increase in vascular permeability which resulted in oedema formation in the tissue was reflected by a large increase in the water and protein content of the tissues, however, there was no increase in either the protein concentration or flow of the lymph. The increases in the total enzyme content in the lesion could not always be related to the macroscopic appearance of the reaction site. However, the severity of the reaction did appear to be related to the concentration of cathepsin D in the oedema fluid present at the reaction site. Although the release of enzymes was reflected in the local lymph in the case of LDH and beta-glucuronidase there was no increase in of the concentration cathepsin D in the lymph draining the lesion.
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PMID:Biochemical and cellular changes in skin and lymph during Arthus and mixed hypersensitivity reactions in rabbits. 13 25

The effects of DMSO are thought to result from the formation of hydrogen bonds with proton-donor groups on biopolymers, which are stronger than those formed with water. Since DMSO contains methyl groups, however, effects on hydrophobic bonding in proteins could be expected at higher DMSO levels. Our studies of the effects of DMSO on model subunit proteins can be interpreted in the above terms. At a concentration of 20% or less, DMSO changed glutamate dehydrogenase into the inactive monomer and the effects were fully reversible with the activator (ADP). Higher DMSO levels resulted in irreversible inactivation. The predominant effect noted on beta-glucuronidase was irreversible inactivation by 20% or more DMSO at 37 degrees C. Purified beta-glucuronidase exhibited an activation in 20% DMSO at high substrate levels; this resulted from an apparent substrate inhibition in the absence of DMSO. DMSO inhibited the clotting of fibrinogen by purified thrombin, but the major effect appeared to be due to competition between thrombin and DMSO for binding sites on fibrinogen. These effects appear to be largely due to interactions between DMSO and hydrophobic bonding in fibrinogen, although DMSO also appears to interfere with the aggregation of fibrin monomers through its effects on hydrophilic groups. These results suggest that reversible alterations in protein structure are the major effect of exposure of subunit proteins to low DMSO levels at low temperatues, while irreversible denaturation of subunit proteins may be an appreciable effect a higher temperatures and higher DMSO concentrations.
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PMID:Effects of dimethyl sulfoxide on subunit proteins. 23 13

The metabolism of benzo[a]pyrene (BP) by hamster embryo cells was studied. The production of water-soluble metabolites, shown to be conjugates with glucuronic acid, depended on BP concentration. With increased BP concentration the amount of glucuronic acid conjugates increased, but the proportion of conjugates in BP or its metabolites present in the medium decreased. The metabolites extracted with ethylacetate were trans-7,8-dihydrodiol-BP (7,8-dihydrodiol) and trans-9,10-dihydrodiol-BP (9,10-dihydrodiol), but large peaks of phenolic metabolites were found by high pressure liquid chromatography (HPLC) after digesting the medium with beta-glucuronidase. Therefore, BP is metabolized to oxygenated forms, and of these, most of the phenolic metabolites and parts of the dihydrodiols are conjugated with glucuronic acid. The proportions of dihydrodiols to phenols, estimated by HPLC after beta-glucuronidase digestion, decreased when the BP concentration was decreased. The results suggest that dihydrodiols are less readily glucuronidated than phenols and so may be metabolized further to metabolites other than glucuronic acid conjugates.
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PMID:Metabolism of benzo[A]pyrene in hamster embryo cells. Effect of the concentration of benzo[A]pyrene on its metabolism. 46 31

[14C] Cholesterol-5 alpha, 6 alpha-expoxide, administered to mice by either gastric intubation or skin painting, was rapidly and primarily excreted in the feces. Residual amonts of the epoxide and its metabolites were found in a wide variety of organs, and persisted for at least 72 hr. At some sites (principally the liver, the small intestinal contents and the combined stomach/duodenum and their contents), the labeled compound existed in a water-soluble form which could not be extracted with chloroform/methanol. Treatment of the small intestinal contents with a preparation of beta-glucuronidase/sulfatase produced a marked increase in the amount of organic-solvent-extractable cholesterol-alpha-epoxide and other polar metabolites. Unchanged epoxide was found mainly in the feces and the skin at the site of application. On the basis of these results, stool specimens, and not blood samples, should be analyzed to detect the presence of this compound and/or its metabolites in vivo.
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PMID:The metabolic fate of cholesterol-5 alpha, 6 alpha-expoxide in vivo. 48 Nov 35


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