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)

Two fluorimetric HPLC methods are described for the quantification of naphthols, phenanthrols and 1-hydroxypyrene (1-OHP) in urine specimens obtained from male Wistar rats exposed to naphthalene, phenanthrene and pyrene. The polycyclic aromatic hydrocarbons (PAHs) were given intraperitoneally, either alone (1.0 mmol/kg body weight) or as an equimolar mixture (0.33 mmol/kg), using the same dosages for repeated treatments on week 1 and week 2. Between these treatments, PAH-metabolizing activities encoded by aryl hydrocarbon (Ah) receptor-controlled genes were induced in the rats with beta-naphthoflavone (betaNF). Chromatographic separation of five phenanthrols (1-, 2-, 3-, 4-, and 9-isomers) was accomplished using two different RP C-18 columns. Despite selective detection (programmable wavelengths), the quantification limits in the urine ranged widely: 1-OHP (0.18 microg/l) <phenanthrols (0.34-0.45 microg/l) <2-naphthol (1.5 microg/l) <1-naphthol (4 micro g/l). The relative standard deviation of the methods was good, as also was the reproducibility. The molar fraction of the dose excreted in 24-h urine as naphthols (<or=4.0%), phenanthrols (<or=1.1%), and 1-OHP (<or=2.4%) was low. Urinary disposition increased differentially in betaNF-induced rats: naphthols, 9-phenanthrol (1- to-2-fold); 2-, 3-, and 4-phenanthrols (4- to 5-fold); 1-phenanthrol and 1-OHP (over 11-fold). The OH-metabolites were analyzed before and after enzymatic hydrolysis (beta-glucuronidase/arylsulfatase). The percentage excreted as a free phenol in urine varied for 1-OHP (2-11%), 1-naphthol (36-51%), 2-naphthol (59-65%), and the phenanthrols (29-94%). 1-Naphthyl- and 1-pyrenyl beta- d-glucuronide served as measures for the completeness of enzymatic hydrolysis. Characteristic differences observed in the urinary disposition of naphthalene, phenanthrene, and pyrene are described, as well as important factors (dose, metabolic capacity, relative urinary output) associated with biomarker validation. This intervention study clarifies intraindividual variation in PAH metabolism and provides useful information for the development of new methods applicable in the biomonitoring of PAH exposure in humans.
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PMID:Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention with beta-naphthoflavone induction in the rat. 1269 33

A single branched isomer of p-nonylphenol, 4(3',6'-dimethyl-3'-heptyl)-phenol, previously identified by gas chromatography-mass spectrometry as one of the major constituent isomers in p-nonylphenol (constituting approximately 10% of all its isomers), was synthesized and used in studies of its bioaccumulation and excretion in the hermophroditic pond snail Lymnaea stagnalis L. Branched isomers of nonylphenol are perceived to have more estrogenlike toxicity than the straight-chain isomers in addition to being more resistant to biodegradation in the environment. With an average static exposure concentration of 104 microg/L (range: 92-116 microg/L) in water at 19 degrees C for 8 d, the uptake of the compound was found to be fairly rapid, reaching a peak concentration of 23,548 microg/kg of whole tissue wet weight after 5 d and a peak bioaccumulation factor (BAFw) of 242 (5,562, based on lipid weight) after 3 d. The uptake data fitted into a logarithmic expression C(t) = 5,231 ln(t) + 11,956, where C(t) is the amount of residues accumulated in whole tissue in micrograms per kilogram tissue wet weight after a period of time, t, and t is the period of exposure in days. By determination of the excretion of 14C-residues released in water and in feces, an average loss of 96% of the accumulated residues was achieved after 22 d of continuous exposure to clean water. By first-order kinetics analysis of the excretion data, an average half-life of excretion of 4.9 d was obtained. By high-performance liquid chromatography and gas-liquid chromatography-mass spectrometry, a catechol metabolite, 4(3',6'-dimethyl-3'-heptyl)-catechol, was detected in tissue extracts (after hydrolysis with beta-glucuronidase) and in feces, in addition to the parent isomer, suggesting that the isomer may have been metabolized by glucuronic acid conjugation and hydroxylation at the ortho position of its phenolic ring.
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PMID:The bioaccumulation and fate of a branched 14C-p-nonylphenol isomer in Lymnaea stagnalis L. 1283 66

Glucuronuria is normal in marsupial folivores such as the koala (Phascolarrctos cinereus), which excretes 2-3 g glucuronic acid daily. Although this has long been attributed to the metabolites of Eucalyptus terpenes, we have found that these are mostly excreted in the unconjugated form. We now report on the aglycones that account for most of the glucuronic acid in koala urine. Urine (24 hr) was collected from six male koalas (8.8 +/- 0.4 kg, mean +/- SE) that were maintained on E. cephalocarpa foliage. Urine samples were analyzed by liquid and gas chromatography (LC and GC) coupled with mass spectrometry (MS). Glucuronides were readily identified by LC-MS/MS, which generated characteristic product ions at m/z 113 and 175. From the corresponding parent glucuronide ions, the masses of the aglycones were calculated. Confirmation of identity was by GC-MS after hydrolysis with beta-glucuronidase and comparison with standard compounds. Quantitation was by GC. The major non-terpene aglycones were 4-methylcatechol, resorcinol, salicyl alcohol, and two unidentified C7H8O2 phenols. Smaller amounts of benzoic acid, benzyl alcohol, orcinol, p-cresol, phenol, and phloroglucinol were detected. We have previously reported that terpene metabolites account for about 10% urinary glucuronides in the same koalas fed E. cephalocarpa. The present study found that an additional 60% urinary glucuronic acid is conjugated with non-terpene, mainly phenolic, aglycones. It seems likely that these phenolic compounds are present in leaves as glycosides and are chiefly responsible for the glucuronuria in koalas.
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PMID:Glucuronuria in the koala. 1291 28

We have investigated the hypothesis that uridine 5'-diphosphate (UDP)-glucuronyltransferases (UGTs) and beta-glucuronidase are jointly involved in a mechanism for the storage and mobilization of iodothyronine metabolites in liver, kidney, heart and brain. Specifically, we predicted UGT activities to decrease and increase respectively, and beta-glucuronidase activity to increase and decrease respectively in hypo- and hyperthyroidism. To this end we have studied the effects of thyroid status on the activities of different enzymes involved in thyroid hormone metabolism in liver, kidney, heart and brain from adult rats with experimentally induced hypo- and hyperthyroidism. We used whole organ homogenates to determine the specific enzyme activities of phenol- and androsteron-UGT, beta-glucuronidase, as well as iodothyronine deiodinase types I and II. Deiodinase type I activities in liver and kidney were decreased in hypothyroid animals and, in liver only, increased in hyperthyroidism. Deiodinase type II activity was increased in hyperthyroid rat kidney only. Interestingly, in the heart, deiodinase type I-specific activity was increased fourfold, although the increase was not statistically significant. Cardiac deiodinase type I activity was detectable but not sensitive to thyroid status. Hepatic phenol-UGT as well as androsteron-UGT activities were decreased in hypothyroid rats, with specific androsteron-UGT activities two to three orders of magnitude lower than phenol-UGT activities. Both UGT isozymes were well above detection limits in heart, but appeared to be insensitive to thyroid status. In contrast, cardiac beta-glucuronidase activity decreased in hypothyroid tissue, whereas the activity of this enzyme in the other organs investigated did not change significantly. In summary, cardiac beta-glucuronidase, albeit in low levels, and hepatic phenol-UGT activities were responsive only to experimental hypothyroidism. Although a high basal activity of the pleiotropic beta-glucuronidase masking subtle activity changes in response to thyroid status cannot be ruled out, we conclude that hepatic, renal and cardiac UGT and beta-glucuronidase activities are not regulated reciprocally with thyroid status.
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PMID:Activities of UDP-glucuronyltransferase, beta-glucuronidase and deiodinase types I and II in hyper- and hypothyroid rats. 1517 87

Urease biogenesis was monitored in the lactic acid bacterium Streptococcus thermophilus during the growth cycle using in-gel detection and a phenol-hypochloride assay. Zymogram analysis, performed in a non-denaturing polyacrylamide gel, enabled visualization of a complex profile of bands whose number and intensity were dependent on the growth phase and culture conditions. The monitoring of urease biogenesis in batch fermentations revealed the onset of enzyme synthesis starting from the mid-exponential growth phase, with a maximum reached during the late exponential phase. Urease activity strongly increased at acidic pH but to a lesser extent when urea and nickel ions were added to the culture medium. When S. thermophilus cells were cultured with pH maintained at a neutral value, urease activity was detectable only in gel with extremely low signals. Evaluation of beta-glucuronidase activity in strain DSM 20617(T) harboring a transcriptional fusion between a DNA fragment containing the putative urease promoter and the gusA reporter evidenced significant expression at neutral pH that strongly increased in an acidic environment. Further experiments carried out on p(ureI)-gusA recombinant strain revealed that expression of ure genes was not affected by carbohydrates, nickel or urea availability. The presence of consistent expression of ure genes at neutral pH and the absence of induction of expression by carbohydrate availability demonstrated that the transcription of ure genes in S. thermophilus is regulated differently compared with that of the closely related S. salivarius. These differences are discussed taking into consideration the different habitats colonized by the two bacterial species.
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PMID:Urease biogenesis in Streptococcus thermophilus. 1602 30

To study the potential hepatic metabolism of olive oil phenols, human hepatoma HepG2 cells were incubated for 2 and 18 h with hydroxytyrosol, tyrosol, and hydroxytyrosyl acetate, three phenolic constituents of olive oil. After incubation, culture media and cell lysates were hydrolyzed with beta-glucuronidase and sulfatase and analyzed by LC-MS. In vitro methylation, glucuronidation, and sulfation of pure phenols were also performed. Methylated and glucuronidated forms of hydroxytyrosol were detected at 18 h of incubation, together with methylglucuronidated metabolites. Hydroxytyrosyl acetate was largely converted into free hydroxytyrosol and subsequently metabolized, yet small amounts of glucuronidated hydroxytyrosyl acetate were detected. Tyrosol was poorly metabolized, with <10% of the phenol glucuronidated after 18 h. Minor amounts of free or conjugated phenols were detected in cell lysates. No sulfated metabolites were found. In conclusion, olive oil phenols can be metabolized by the liver as suggested by the results obtained using HepG2 cells as a hepatic model system.
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PMID:Metabolism of the olive oil phenols hydroxytyrosol, tyrosol, and hydroxytyrosyl acetate by human hepatoma HepG2 cells. 1636 72

Due to its low digestibility in the small intestine, a major fraction of the polyol isomalt reaches the colon. However, little is known about effects on the intestinal microflora. During two 4-week periods in a double-blind, placebo-controlled, cross-over design, nineteen healthy volunteers consumed a controlled basal diet enriched with either 30 g isomalt or 30 g sucrose daily. Stools were collected at the end of each test phase and various microbiological and luminal markers were analysed. Fermentation characteristics of isomalt were also investigated in vitro. Microbiological analyses of faecal samples indicated a shift of the gut flora towards an increase of bifidobacteria following consumption of the isomalt diet compared with the sucrose diet (P<0.05). During the isomalt phase, the activity of bacterial beta-glucosidase decreased (P<0.05) whereas beta-glucuronidase, sulfatase, nitroreductase and urease remained unchanged. Faecal polyamines were not different between test periods with the exception of cadaverine, which showed a trend towards a lower concentration following isomalt (P=0.055). Faecal SCFA, lactate, bile acids, neutral sterols, N, NH3, phenol and p-cresol were not affected by isomalt consumption. In vitro, isomalt was metabolized in several bifidobacteria strains and yielded high butyrate concentrations. Isomalt, which is used widely as a low-glycaemic and low-energy sweetener, has to be considered a prebiotic carbohydrate that might contribute to a healthy luminal environment of the colonic mucosa.
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PMID:Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers. 1644 15

The synthesis and biological evaluation of novel prodrugs based on the cytotoxic antibiotic duocarmycin SA (1) for a selective treatment of cancer using a prodrug monotherapy (PMT) are described. Transformation of the phenol 8 with the glucuronic acid benzyl ester trichloroacetimidate 9b followed by reaction with DMAI x HCl (10) gives the glucuronide 11b, which is deprotected to afford the desired prodrug 4a containing a glucuronic acid moiety. In addition, the prodrug 4b with a glucuronic methyl ester unit is prepared. The cytotoxicity of the glucuronides is determined using a HTCFA-assay with IC(50) values of 610 nM for 4a and 3300 nM for 4b. In the presence of beta-glucuronidase, 4a expresses an IC(50) value of 0.9 nM and 4b of 2.1 nM resulting in QIC(50) values of about 700 for 4a and 1600 for 4b.
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PMID:Duocarmycin-based prodrugs for cancer prodrug monotherapy. 1852 5

We have developed an analytical method for the determination of urinary 5-chloro-2-(2,4-dichlorophenoxy)phenol (triclosan), which utilizes stir bar sorptive extraction (SBSE) and thermal desorption (TD)-gas chromatography-mass spectrometry (GC-MS). Human urine sample is de-conjugated by treatment with beta-glucuronidase and sulfatase. A stir bar coated with polydimethylsiloxane (PDMS) is added to the urine sample in a vial and the sample is stirred for 60 min at room temperature (25 degrees C). Then, the PDMS stir bar is subjected to TD-GC-MS. The detection limit of triclosan is 0.05 ng mL(-1). The method shows linearity over the calibration range (0.1-10 ng mL(-1)) and the correlation coefficient (r) is higher than 0.993 for triclosan standard solution. The average recoveries of triclosan in human urine sample are 102.8-113.1% (RSD: 2.4-6.7%). This simple, sensitive, and selective analytical method may be used in the determination of trace amounts of triclosan in human urine samples.
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PMID:Determination of urinary triclosan by stir bar sorptive extraction and thermal desorption-gas chromatography-mass spectrometry. 1895 22

The formation of cell- and medium-associated metabolites of 7,12-dimethylbenz[a]anthracene (DMBA) by primary mouse epidermal cells was examined using high-pressure liquid chromatography. Cells were cultured in the presence of 14C DMBA for various time periods prior to harvesting. Ethyl acetate/acetone (2:1) extractable metabolites found associated with cells cochromatographed with 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA), 12-hydroxymethyl-7-methylbenz[a]anthracene (12-OHM-7-MBA), (+/-)-trans-3,4-dihydro-3,4-dihydroxy-7,12-dimethylbenz[a]anthracene ((+/-)-trans-DMBA-3,4-diol) and phenols. The major metabolite(s) found within cells cochromatographed with DMBA-phenol(s). Ethyl acetate/acetone extractable metabolites found in the medium cochromatographed with 7-OHM-12-MBA, 12-OHM-7-MBA, (+/-)-trans-DMBA-3,4-diol, (+/-)-trans-8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz[a]anthracene ((+/-) -trans-DMBA-8,9-diol) and phenols. The major ethyl acetate/acetone soluble metabolite found in the medium cochromatographed with (+/-)-trans-DMBA-8,9-diol. This metabolite is rapidly excreted unchanged from the cells into the medium. In addition, primary epidermal cells rapidly converted 14C DMBA to water soluble metabolites that could not be extracted from the medium with ethyl acetate/acetone. Approximately 50% of these water soluble metabolites were extractable with organic solvent upon treatment of the medium with beta-glucuronidase. Phenolic metabolite(s) represented 75-85% of the total beta-glucuronidase releasable material. The results indicated that primary mouse epidermal cells in culture rapdly converted DMBA to a variety of hydroxylated products some of which were conjugated with glucuronic acid. In addition, the formation of (+/-)-trans-DMBA-3,4-diol and its retention within the cells provides additional support for an important role for this metabolite in carcinogenesis by DMBA.
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PMID:Biotransformation of 7,12-dimethylbenz[alanthracene by mouse epidermal cells in culture. 2228 79


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