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)

1. An investigation was carried out on the hydrolytic activity of the intestinal mucus/flora on phenylglucuronide in the bile of goldfish. 2. Approximately 79% of the total phenylglucuronide (3.4 mumol) in the bile was hydrolysed after 16 h incubation with the intestinal mucus/flora. 3. Of the total phenol in the aquarium water of goldfish exposed previously to phenol for 48 h, 41% was found to be phenylglucuronide when fish were placed in a phenol-free medium and were dosed hourly for 8 h with D-saccharic acid 1,4-lactone to inhibit beta-glucuronidase activity in the intestine.
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PMID:Hydrolysis of the biliary glucuronic acid conjugate of phenol by the intestinal mucus/flora of goldfish (Carassius auratus). 685 97

A rapid and sensitive radioassay for measuring UDP-glucuronosyltransferase activities (EC 2.4.1.17) toward the major endogenous substrates hyodeoxycholic and hyocholic acids, bilirubin, estriol, androsterone, and testosterone has been developed. In this assay, 14C-labeled glucuronides are formed from the enzyme-catalyzed reaction of 14C-labeled UDP-glucuronic acid with the unlabeled aglycones. Following incubation, the 14C-labeled glucuronides are separated under acidic conditions from the unreacted 14C-labeled UDP-glucuronic acid by a single extraction with ethyl acetate. The recovery of glucuronides into ethyl acetate was greater than 90%, whereas the carryover of unreacted UDP-glucuronic acid into the organic phase was approximately 0.2%. The reaction products extracted into ethyl acetate were characterized by their mobilities in thin-layer chromatography and identified as glucuronides by their sensitivity to hydrolysis with beta-glucuronidase and inhibition of hydrolysis by the specific beta-glucuronidase inhibitor D-saccharic acid-1,4-lactone. The optimal conditions of enzyme reactions with the individual aglycones have been defined with human liver microsomes as enzyme source. For all aglycones investigated, 10-30 micrograms of microsomal protein are sufficient for enzyme estimation. The assay is applicable to biochemical studies of UDP-glucuronosyltransferases, as well as to measurement of these enzyme activities from small amounts of clinical liver specimens.
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PMID:Radioassay of UDP-glucuronosyltransferase activities toward endogenous substrates using labeled UDP-glucuronic acid and an organic solvent extraction procedure. 808 74

D-Glucarate has shown modest chemopreventive and synergistic chemopreventive effects with retinoids in a number of tumor models as well as a similar antiproliferative effect in MCF-7 human tumor cells in culture. It has been postulated that D-glucarate exerts some of its effects by equilibrium conversion to D-glucarolactone, a potent beta-glucuronidase inhibitor. In the present study, D-glucarate and a number of its analogues, including D-glucarolactone, were evaluated as antiproliferatives in the MCF-7 model with and without added retinoid. Results suggest that the effects of glucarate are reasonably specific for its structure and may not require conversion to glucarolactone.
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PMID:Activity of D-glucarate analogues: synergistic antiproliferative effects with retinoid in cultured human mammary tumor cells appear to specifically require the D-glucarate structure. 819 1

The in vitro formation rates of the phenolic (DPG) and acyl (DAG) glucuronides of diflunisal were investigated using rat liver microsomes. Preliminary studies showed that DAG hydrolysed rapidly (T1/2 = 12 min) when incubated in the presence of rat liver microsomes at pH 7.4 and 37 degrees. DPG was much more stable under the same conditions (T1/2 = 35 hr). Hydrolysis of DAG and DPG by rat liver microsomes was inhibited by 4 mM saccharolactone, a beta-glucuronidase inhibitor. The apparent Km and Vmax values for the formation of DAG in the absence and presence of 4 mM D-saccharic acid-1,4-lactone (saccharolactone) were the following: Km = 0.05 +/- 0.02 vs 0.08 +/- 0.02 mM and Vmax = 0.20 +/- 0.06 vs 0.43 +/- 0.07 nmol/min/mg protein (0 and 4 mM saccharolactone, respectively). The significant increase in apparent Vmax for DAG formation in the presence of saccharolactone can be explained by the inhibition of beta-glucuronidase-catalysed hydrolysis of DAG. Apparent Km and Vmax values for the formation rate of DPG were not affected by addition of saccharolactone to the incubation medium. These results indicate that beta-glucuronidase-catalysed hydrolysis of certain glucuronides formed during microsomal incubations may significantly affect the apparent glucuronidation rate due to the presence of a glucuronidation-deglucuronidation cycle.
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PMID:Glucuronidation of diflunisal by rat liver microsomes. Effect of microsomal beta-glucuronidase activity. 826 44

An endogenous beta-glucuronidase that hydrolyses the chromogenic substrate 5-bromo-4-chloro-3-indolyl-beta-D-glucuronide (X-gluc) in Aspergillus niger is reported. The activity was induced when the fungus was grown in media containing xylan, but was either very low, or absent, when grown on glucose. Endogenous beta-glucuronidase was primarily located in newly formed hyphae, and was apparent at pH values between 3 and 6. Hydrolysis of X-gluc was sensitive to the inhibitor D-saccharic acid 1,4-lactone and was irreversibly inactivated by heating. The bacterial uid A beta-glucuronidase reporter gene was strongly expressed in the hyphae of transformed A. niger but, in contrast to the endogenous activity, the enzyme was also active at pH 7-8.5. Histochemical localization of uidA expression in A. niger, without interference from the endogenous beta-glucuronidase activity, was achieved by staining at this pH.
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PMID:Detection of endogenous beta-glucuronidase activity in Aspergillus niger. 892 Jan 95

D-Glucaric acid (GA) is a nontoxic, natural compound. One of its derivatives is the potent beta-glucuronidase inhibitor D-glucaro-1,4-lactone (1,4-GL). The goal of this study was to demonstrate the in vivo formation of 1,4-GL from a D-glucarate salt and determine its metabolism, uptake by selected organs, and excretion following oral administration of potassium hydrogen D-[14C]glucarate to male and female Sprague-Dawley rats. 1,4-GL increases detoxification of carcinogens and tumor promoters/progressors by inhibiting beta-glucuronidase and preventing hydrolysis of their glucuronides. 1,4-GL and its precursors, such as potassium hydrogen D-glucarate and calcium D-glucarate, may exert their anticancer action, in part, through alterations in steroidogenesis accompanied by changes in the hormonal environment and the proliferative status of the target organ. Thus, GA derivatives may be useful as new or adjuvant cancer preventive and therapeutic agents. In our study, 1,4-GL was found to be formed from the D-glucarate salt in the stomach of rats. It was apparently absorbed from the gastrointestinal tract, transported with the blood to different internal organs, and excreted in the urine and to a lesser extent in bile. There were no significant differences in the metabolism of PHG between male and female rats. Thus, formation of 1,4-GL from D-glucaric acid derivatives may be prerequisite for their inhibition of chemical carcinogenesis in rodents and prevention of breast, prostate, and colon cancer in humans.
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PMID:Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention. 910 Oct 79

Most commercially available test kits for water and foodstuffs use beta-galactosidase activity for coliforms and beta-glucuronidase activity for Escherichia coli. We tested the effects on the beta-glucuronidase activity of E. coli W3110 of substances usually present in foods and several synthetic pharmaceutical compounds. Thirteen substances were tested: three carbohydrates, four flavonoids, five monosaccharide derivatives, and dimethyl sulphoxide. In a minimum medium without any other carbon source, glucose (0.1 mM), quercetin (0.1 mM), silymarin (10 mg/L), D-gluconic acid (0.01 mM), D-gluconic acid lactone (0.01 mM), isopropyl-beta-D-thiogalacto pyranoside (1 mM), p-nitrophenyl beta-D-glucuronide (1 mM), and DMSO (1 M) completely inhibited E. coli glucuronidase activity at the above concentrations. However, the following compounds stimulated E. coli glucuronidase activity within the ranges of concentrations shown: glucose (0.0001-0.01 mM), lactose and sucrose (>0.1 mM), D-saccharic acid 1,4 lactone (0.0001-0.1 mM), p-nitrophenyl beta-D-glucuronide (0.001-0.01 mM) and DMSO (2-500 mM). In a rich culture medium that contained other carbon sources (lauryl tryptose broth) E. coli glucuronidase activity in the presence of the extra nutrients was unaffected by the test substances and therefore, under normal conditions in water or foods, they should not interfere with E. coli assays based on measurements of beta-glucuronidase activity.
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PMID:Interference by carbohydrate substrates, flavonoids, and monosaccharide derivatives on bacterial beta-D-glucuronidase assays. 977 76

While calcium D-glucarate was shown to inhibit chemical carcinogenesis in various animal models, the effect of potassium hydrogen D-glucarate has not been extensively investigated. In the present study, potassium hydrogen D-glucarate markedly inhibited azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. Potassium hydrogen D-glucarate (PHG) or potassium hydrogen carbonate (PHC) were administered to rats in a diet (140 mmol/kg). Continual post-initiation treatment with potassium hydrogen D-glucarate reduced both tumor incidence and multiplicity at sacrifice by ca. 60%, while PHC had no effect. amelioration of overexpression of the betaG gene in rat colon carcinomas was observed using RT-PCR and Northern blot analysis. We hypothesize that previously demonstrated conversion of PHG to D-glucaro-1,4-lactone, a potent inhibitor of beta-glucuronidase (betaG), may be responsible for this effect. The mechanism of PHG inhibition of colon carcinogenesis may also involve suppression of cell proliferation and possibly alterations in cholesterol synthesis or cholesterol metabolism to bile acids. In conclusion, PHG possesses excellent potential as a natural, apparently non-toxic inhibitor to prevent colon cancer.
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PMID:Inhibition of azoxymethane-induced rat colon carcinogenesis by potassium hydrogen D-glucarate. 1060 47

Microchip capillary electrophoresis (CE) was used with a model enzyme assay to demonstrate its potential application to combinatorial drug screening. Hydrolysis with beta-glucuronidase of the conjugated glucuronide, fluorescein mono-beta-D-glucuronide (FMG), liberated the fluorescent product, fluorescein. FMG and fluorescein were detected by fluorescence, with excitation and emission at 480 and 520 nm, respectively. Microchip CE was used to separate FMG and fluorescein. Fluorescein production was monitored to assess beta-glucuronidase activity. Michaelis-Menten enzyme kinetics analysis yielded the Km value. The results were compared with those from experiments done by conventional CE. The Km value for beta-glucuronidase with FMG is being reported for the first time as 18 microM. The inhibition of beta-glucuronidase by the competitive inhibitor D-saccharic acid-1,4-lactone (SL) was also determined using microchip CE. Reactions were done with various concentrations of inhibitor and constant beta-glucuronidase and FMG concentrations. A dose-response plot was acquired and the IC50 value for SL was determined to be 3 microM.
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PMID:Fluorogenic assay for beta-glucuronidase using microchip-based capillary electrophoresis. 1158 56

The fecal beta-glucuronidase activity of patients with colon cancer and healthy controls were measured to determine the relationship between the fluctuation of intestinal bacterial beta-glucuronidase and colon cancer. The fecal beta-glucuronidase activity of patients with colon cancer was 1.7 times higher than that of the healthy controls. However, when these fecal specimens were sonicated, the enzyme activity of patients with colon cancer was 12.1 times higher than that of the healthy controls. The fecal beta-glucuronidase activity of human intestinal bacteria was drastically induced by its substrate or the bile secreted after a subcutaneous injection of 1,2-dimethylhydrazine (DMH) and benzo[a]pyrene into rats. DMH- and benzo[a]pyrene-treated biles induced beta-glucuronidase activity in the human intestinal microflora by approximately 1.5- and 2.3-fold, respectively. They also induced beta-glucuronidase in E. coli HGU-3, which is a beta-glucuronidase-producing bacterium from the human intestine. D-saccharic acid 1,4-lactone similarly inhibited fecal beta-glucuronidase in several patients with colon cancer in addition to the healthy controls. This suggests that potent beta-glucuronidase activity is a prime factor in the etiology of colon cancer.
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PMID:Intestinal bacterial beta-glucuronidase activity of patients with colon cancer. 1179 36


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