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)

The mutagenicity of 2-hydroxylamino-4-nitrotoluene (2HA4NT), 4-hydroxylamino-2-nitrotoluene (4HA2NT), 2-hydroxylamino-6-nitrotoluene (2HA6NT) or 4-acetylamino-2-hydroxylaminotoluene (4AA2HAT) towards Salmonella typhimurium strains TA98 and TA100 was investigated in the absence and presence of uridine-5'-diphosphoglucuronic acid (UDPGA), acetyl CoA or 3'-phosphoadenosine-5'-phosphosulfate (PAPS) systems, or S9 mix. None of the hydroxylaminonitrotoluenes (2HA4NT, 4HA2NT or 2HA6NT) were mutagenic in both strains while 4AA2HAT was a base-pair substitution mutagen in the UDPGA and PAPS systems. The indirect mutagenic activity was markedly decreased by omission of microsomal fraction (MCF) or UDPGA from the UDPGA system and by addition of beta-glucuronidase to the system. Similarly, the mutagenic activity was markedly decreased either when 105000 X g supernatant fluid (S105), adenosine triphosphate (ATP) or Na2SO4 was omitted from the PAPS system or when pentachlorophenol (PCP) or aryl sulphatase was added to the system. Moreover, the mutagenic activity in either system was markedly decreased by the addition of glutathione (GSH). These results suggested that two esterifications with glucuronic acid and sulfuric acid may play an important role in the appearance of mutagenic activity of 4AA2HAT.
 ...
PMID:Mutagenicity of some hydroxylaminotoluene derivatives towards Salmonella typhimurium in esterification systems. 355 29

Carbamazepine 10,11-oxide (1a,10b-dihydro-6H-dibenzo[b,f]oxireno[d]azepine-6-carboxamide), a key intermediate in carbamazepine metabolism, was found to be unusually resistant to enzymatic hydrolysis when incubated with microsomal and cytosolic fractions from rabbit, rat, and guinea pig livers. However, its hydrolysis product, trans-10,11-dihydro-10,11-dihydroxy-5H-dibenzo[b,f]azepine-5-carboxamide , was excreted, as previously reported, both in the free and in conjugated forms, as the main metabolite in the urine of humans under carbamazepine treatment. The free diol and that obtained after treatment with beta-glucuronidase/arylsulfatase were both found by Mosher's method to be formed in an enantiomeric excess of 80%, the prevalent enantiomer having the (-)-10S,11S absolute configuration, as determined by applying the CD exciton coupling method to its bis[p-(dimethylamino)benzoyl] ester. This finding confirms the pronounced enantioselectivity of the microsomal epoxide hydrolase toward meso and racemic substrates, but is in contrast with the prevalent formation of (R,R)-diols in most other known cases of enzymatic hydrolysis of epoxides. Preparatively useful syntheses of the racemic trans-10,11-dihydro-10,11-diol and of 9-(hydroxymethyl)-10-carbamoylacridan, another carbamazepine metabolite, are reported for the first time.
 ...
PMID:The metabolism of carbamazepine in humans: steric course of the enzymatic hydrolysis of the 10,11-epoxide. 357 65

Liver beta-glucuronidase is structurally altered in inbred strain PAC so that a peptide subunit with a more basic isoelectric point, GUS-SN, is produced. This allele of beta-glucuronidase was transferred to strain C57BL/6J by 12 backcross matings to form the congenic line B6 X PAC-Gus(n). Liver beta-glucuronidase activity was halved in males of the congenic strain compared to normal males. The lowered activity was specifically accounted for by a decrease in the lysosomal component. There was no alteration in the concentration of microsomal activity. This alteration in the subcellular distribution of beta-glucuronidase in Gus(n)/Gus(n) mice was confirmed by two independent gel electrophoretic systems which separate microsomal and lysosomal components. beta-Glucuronidase activity was likewise approximately halved in mutant spleen, lung, and brain, organs which contain exclusively or predominantly lysosomal beta-glucuronidase. The loss of liver lysosomal beta-glucuronidase activity was shown by immunotitration to be due to a decrease in the number of beta-glucuronidase molecules in lysosomes of the congenic strain. The Gus(n) structural alteration likely causes the lowered lysosomal beta-glucuronidase activity since the two traits remain in congenic animals. Heterozygous Gus(n)/Gus(b) animals had intermediate levels of liver beta-glucuronidase. Also, the effect was specific, in that three other lysosomal enzymes were not reproducibly lower in Gus(n)/Gus(n) mice. Gus(n) is, therefore, an unusual example of a mutation which causes a change in the subcellular distribution of a two-site enzyme.
 ...
PMID:Abnormal subcellular distribution of beta-glucuronidase in mice with a genetic alteration in enzyme structure. 357 66

Rat hepatic microsomal preparations were used to study the metabolism of deoxynivalenol (DON) and its metabolite 3 alpha,7 alpha,15-trihydroxytrichothec-9,12-dien-8-one (DOM-1). The N-demethylation of ethylmorphine was monitored to assess the viability of the mixed-function oxidase. DON was incubated with microsomes and an NADPH-generating system. Samples were removed from the incubation system and analysed for DON using an HPLC equipped with a UV detector. After incubation for 30 min, there was no evidence of disappearance of DON or of the presence of new metabolites; neither was microsomal NADPH oxidation altered by the addition of DON. Rat and pig hepatic microsomal preparations were used to assess DON glucuronidation, using p-nitrophenol disappearance to check the viability of the microsomal glucuronidating system. When DON was incubated with microsomes and 14C-labelled uridine 5'-diphosphoglucuronic acid, no radioactivity was detected in the TLC zone where the glucuronide was expected. Three rats and one pig were dosed orally with 2 mg DON/kg and samples of their urine and faeces were extracted and incubated with beta-glucuronidase or with buffer only. No differences in DON or DOM-1 concentrations were detected between samples incubated with or without beta-glucuronidase. These results suggest that DON was neither bioactivated to a more toxic product nor oxidized to a less toxic compound by the rat hepatic mixed-function oxidase system. Likewise, DOM-1 was not reactivated or metabolized by this system. Neither DON nor DOM-1 glucuronides were formed either in in vitro liver systems or in vivo.
 ...
PMID:Lack of hepatic microsomal metabolism of deoxynivalenol and its metabolite, DOM-1. 358 56

Organophosphorous compounds, which are potent inhibitors of egasyn-esterase activity, caused a rapid dissociation of the high molecular weight egasyn-microsomal beta-glucuronidase complex when administered in vivo or when added in vitro to microsomal suspensions. The dissociation was relatively specific to phosphodiester inhibitors of the esterase active site. Also, the egasyn-esterase active site was inaccessible to substrates and to inhibitors when egasyn was complexed to beta-glucuronidase. Dissociation of the egasyn-microsomal beta-glucuronidase complex in vivo by organophosphorous compounds was followed by massive and rapid secretion of microsomal beta-glucuronidase, but not egasyn, into plasma. These experiments implicate the egasyn-esterase active site in attachment of microsomal beta-glucuronidase to egasyn by a novel mechanism that, in turn, compartmentalizes beta-glucuronidase within the endoplasmic reticulum.
 ...
PMID:Involvement of the esterase active site of egasyn in compartmentalization of beta-glucuronidase within the endoplasmic reticulum. 359 74

Mouse liver beta-glucuronidase is stabilized within microsomal vesicles by complexation with the accessory protein egasyn. The location of the beta-glucuronidase-egasyn complex and free egasyn within microsomal vesicles was investigated. Surprisingly, it was found that neither the complex nor free egasyn are intrinsic membrane components. Rather, both are either free within the vesicle lumen or only weakly bound to the inside of the vesicle membrane. This conclusion was derived from release studies using low concentrations of Triton X-100 or controlled sonication. Both the intact complex and free egasyn were released in parallel with lumenal proteins, not with intrinsic membrane components. Also, beta-glucuronidase was protected from digestion by proteinase K by the membrane of microsomal vesicles. The hydrophilic nature of both the complex and free egasyn was confirmed by phase separation experiments with the detergent Triton X-114. Egasyn is one of an unusual group of esterases that, despite being located within the lumen or only weakly bound to the lumenal surface of the endoplasmic reticulum, do not enter the secretory pathway.
 ...
PMID:Lumenal location of the microsomal beta-glucuronidase-egasyn complex. 366 91

The urinary mutagenicity and the excretion of polycyclic aromatic hydrocarbons (PAH) in three non-smoking male patients, treated for psoriasis with cutaneous applications of crude coal tar, were analysed. Mutagenicity of the urinary extracts was measured by the plate incorporation assay using Salmonella typhimurium strains TA 98 and TA 100 in the presence of liver S9 fraction from Aroclor-induced rats with or without beta-glucuronidase. After concentration, hydrolysis and reduction of the urine sample, PAH levels were measured by high resolution gas chromatography/mass spectrometry. Following cutaneous treatment with coal tar, the urine of all three subjects showed noticeable levels of PAH and/or metabolites and marked mutagenicity both on strain TA 98 and TA 100 in the presence of S9 fraction. The addition of beta-glucuronidase increased the mutagenicity of the urinary extracts, the maximum values being attained on strain TA 100 in the presence of both microsomal fraction and deconjugating enzymes. The mutagenicity of urinary extracts from subjects treated therapeutically with crude coal tar was correlated (r = 0.788, P less than 0.01) with the total PAH levels in their urine. The PAH excreted in urine were mainly low molecular weight compounds, while benzo[a]anthracene was present in scarce amounts and the excretion of benzo[a]pyrene did not increase following the cutaneous exposure to the crude coal tar.
 ...
PMID:Mutagenic activity and polycyclic aromatic hydrocarbon levels in urine of humans exposed to therapeutical coal tar. 369 8

The mutagenic activity of urine samples from nonsmoking individuals before and after the consumption of either red wine or grape juice was determined. Urine samples collected from individuals on liquid or regular diets were concentrated using XAD-2 resin. No mutagenic activity of urine concentrates was detected with Salmonella tester strains TA98 or TA100 with or without microsomal activation. The addition of 1000 units of beta-glucuronidase into the agar overlay did not show any mutagenic activity. The mutagens in red wine and grape juice, however, were extracted using the XAD-2 column. Concentrates of urine samples spiked with either of the two extracts exhibited mutagenic activity.
 ...
PMID:Dietary factors affecting the urinary mutagenicity assay system. II. The absence of mutagenic activity in human urine following consumption of red wine or grape juice. 388 35

Lysosomal enzymes have been shown to be synthesized as microsomal precursors, which are processed to mature enzymes located in lysosomes. We examined the effect of ammonium chloride on the intracellular processing and secretion of two lysosomal enzymes, beta-glucuronidase and beta-galactosidase, in mouse macrophages. This lysosomotropic drug caused extensive secretion of both precursor and mature enzyme forms within a few hours, as documented by pulse radiolabeling and molecular weight analysis. The normal intracellular route for processing and secretion of precursor enzyme was altered in treated cells. A small percentage of each precursor was delivered to the lysosomal organelle slowly. Most precursor forms traversed the Golgi apparatus, underwent further processing of carbohydrate moieties, and were then secreted in a manner similar to secretory proteins. The lag time for secretion of newly synthesized beta-galactosidase precursor was notably longer than that for the beta-glucuronidase precursor. The source of the secreted mature enzyme was the lysosomal organelle. Macrophages from the pale ear mutant were markedly deficient in secretion of mature lysosomal enzyme but secreted precursor forms normally. These results suggest that ammonia-treated macrophages contain two distinct intracellular pathways for secretion of lysosomal enzymes and that a specific block in the release of lysosomal contents occurs in the pale ear mutant.
 ...
PMID:Effects of ammonia on processing and secretion of precursor and mature lysosomal enzyme from macrophages of normal and pale ear mice: evidence for two distinct pathways. 392 95

The distribution of glucuronidation capacity along the rat intestine was investigated using mucosal cells, isolated from the small intestine, the caecum, and the colon plus rectum. The glucuronidation capacity for 1-naphthol decreases from 787 +/- 75 (duodenum) to 128 +/- 13 (colon plus rectum) pmoles/min X mg cell protein. The ratio between 1-naphthol and morphine glucuronidation was constant throughout the intestine (7.15 +/- 0.37). The distribution of maximal activity of UDP-glucuronosyltransferase in intestinal cell homogenates follows the same pattern. The maximal activity of UDPglucose dehydrogenase in homogenates corresponds closely to the glucuronidation rate in mucosal cells. The activity of beta-glucuronidase in intestinal cell homogenates is constant along the duodenum and jejunum but increases throughout the terminal ileum, caecum, colon and rectum. Subcellular fractionation studies using marker enzymes indicate that UDPglucose dehydrogenase and beta-glucuronidase are cytosolic enzymes in intestinal mucosal cells. Although UDP-glucuronosyltransferase activity is found in both the mitochondrial and the microsomal fractions, no indications for a mitochondrial localization of this enzyme can be found. Activity in the mitochondrial fraction appears to be due to endoplasmic reticulum, associated with the mitochondrial fraction.
 ...
PMID:Distribution of glucuronidation capacity (1-naphthol and morphine) along the rat intestine. 393 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>