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)

Biotransformation of 3-(2',4',5'-triethoxybenzoyl)propionic acid (tri-, ethoxybenzoylpropionate) was studied in man using isotopic cluster technique. From the 24 h urine of a male volunteer given an equimolar mixture of non-labelled and pentadeuterium-labelled triethoxybenzoylpropionate (1 mg/kg) orally, the parent drug, 3-(2',5'-diethoxy-4'-hydroxybenzoyl)propionic acid (4'-phenol) and 3-(2',4'-diethoxy-5'-hydroxybenzoyl)propionic acid (5'-phenol) were isolated and identified by g.l.c.-mass spectrometry. 2. Urinary components were also quantified by mass chromatography: the parent drug (67.4% of dose) and 4'- and 5'-phenols in a mixture (20.3%). More than 80% of urinary triethoxybenzoylpropionate was present as its glucuronic acid ester, as evidenced by using beta-glucuronidase and saccharo-1,4-lactone, a specific inhibitor of the enzyme. Almost all of 4'- and 5'-phenols appeared as conjugates with glucuronic acid and/or sulphuric acid. These findings indicated that in man triethoxybenzoylpropionate was largely conjugated with glucuronic acid and in part underwent deethylation followed by conjugation for elimination mainly in urine.
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PMID:Human urinary metabolites of 3-(2',4',5'-triethoxybenzoyl)propionic acid, a new biliary smooth muscle relaxant with choleretic activity. 72 17

We studied the effect on fecal hydrolytic activities of adopting an uncooked extreme vegan diet and readopting a conventional diet. Eighteen subjects were randomly divided into test and control groups. In the test group subjects adopted the uncooked extreme vegan diet for 1 mo and then resumed a conventional diet for a second month. Controls consumed a conventional diet throughout the study. Phenol and p-cresol concentrations in serum and daily output in urine and fecal enzyme activities were measured. The activity of fecal urease significantly decreased (by 66%) as did cholylglycine hydrolase (55%), beta-glucuronidase (33%) and beta-glucosidase (40%) within 1 wk of beginning the vegan diet. The new level remained throughout the period of consuming this diet. Phenol and p-cresol concentrations in serum and daily outputs in urine significantly declined. The fecal enzyme activities returned to normal values within 2 wk of resuming the conventional diet. Concentrations of phenol and p-cresol in serum and daily output in urine had returned to normal after 1 mo of consuming the conventional diet. No changes were observed in the control group during the study. Results suggest that this uncooked extreme vegan diet causes a decrease in bacterial enzymes and certain toxic products that have been implicated in colon cancer risk.
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PMID:Shifting from a conventional diet to an uncooked vegan diet reversibly alters fecal hydrolytic activities in humans. 155 66

The effects of dietary Konjac mannan (KM), a frequent ingredient of traditional Japanese foods, on intestinal microbial metabolism and microflora composition were investigated using two laboratory animal models, namely, conventional F344 rats and C3H/He male mice bearing human flora. Dietary KM led to a significant reduction in faecal beta-glucuronidase, nitroreductase and azoreductase activities, and in the production of phenol and indole in the faeces of conventional F344 rats. In the C3H/He male mice bearing human flora, faecal beta-glucuronidase and nitroreductase activities were significantly reduced by KM ingestion, as were the amounts of the putrefactive products, p-cresol and indole, in the faeces. Slight differences in intestinal microflora composition between control and KM diet groups were noted. The results indicate that, in C3H/He male mice bearing human flora, dietary KM may modify microbial metabolism without causing significant alterations in intestinal microflora composition.
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PMID:Effect of Konjac mannan on intestinal microbial metabolism in mice bearing human flora and in conventional F344 rats. 165 42

Long-chain fatty acids inhibit glucuronidation of benzo(a)pyrene phenols in perfused liver; therefore, this study was designed to investigate interactions of fatty acids with beta-glucuronidase, glucuronosyl transferase, and energy supply. In beta-glucuronidase-deficient C3H/He mice, infusion of oleate (250 microM) increased the release of free benzo(a)pyrene phenols from 14 to 33 nmol/g/h and decreased release of glucuronides into the perfusate from 25 to 17 nmol/g/h. Rates of accumulation of glucuronides in the liver were also diminished from 11 to 4 nmol/g/h after infusion of oleate (250 microM). Fatty acids did not affect the release of benzo(a)pyrene metabolites into bile, and the ratio of free phenol to glucuronide production was increased from 0.57 to 1.30. A similar trend was observed in livers from DBA/2 mice that have beta-glucuronidase. Rates of hydrolysis of benzo(a)pyrene-O-glucuronide were not altered in isolated microsomes by addition of oleoyl coenzyme A (CoA) or octanoyl CoA (10- approximately 100 microM). Thus, we conclude that fatty acids do not alter glucuronidation by acting on beta-glucuronidase. The concentration of cofactors (UDP-glucuronic acid, UDP-glucose, and adenine nucleotides) involved in hepatic conjugation was not altered by infusion of concentrations of oleate (300 microM) that inhibited glucuronidation in perfused livers. When oleate concentrations were increased to 600 microM, UDP-glucuronic acid and UDP-glucose decreased 44 and 49%, respectively, and the ATP:ADP ratio declined concomitantly. Oleoyl CoA inhibited UDP-glucuronosyl transferase noncompetitively (half-maximal inhibition, 10 microM) in microsomes with 3-hydroxy-benzo(a)pyrene or p-nitrophenol as substrate. In contrast, octanoyl CoA was a very poor inhibitor of transferase activity. Inhibition of the transferase by oleoyl CoA was increased markedly by treatment with detergents (Triton X-100), i.e., half-inhibition of glucuronosyl transferase was obtained with about 2 microM oleoyl CoA. Inhibition of UDP-glucuronosyl transferase by oleoyl CoA was also increased in a dose-dependent manner by albumin, possibly due to increasing access of the CoA derivative to the enzyme. Collectively, these data indicate that fatty acids diminish glucuronidation via the formation of acyl CoA compounds that inhibit UDP-glucuronosyl transferase noncompetitively.
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PMID:Inhibition of glucuronidation of benzo(a)pyrene phenols by long-chain fatty acids. 190 48

1. The in vivo biliary metabolites of (+/-)-3-dimethylamino-1,1-diphenylbutane hydrochloride (recipavrin) isolated from Wistar rats have been characterized by g.l.c.-mass spectrometry. 2. Non-conjugated metabolites include recipavrin (1), norrecipavrin (2), diphenylbutanone (3), diphenylbutanone oxime (4), diphenylbutanone phenol (12), diphenylbutanone oxime phenol (14), recipavrin phenol (19), diphenylbutanone O-methylcatechol (16) and diphenylbutanone oxime O-methylcatechol (18). 3. Following beta-glucuronidase hydrolysis and extraction from pH 10 solution, diphenylbutanone (3), diphenylbutanone oxime (4), an unidentified compound (6), primary amine (8), norrecipavrin (2), recipavrin (1), phenols (12, 14, 15), norrecipavrin phenol (13), O-methylcatechols (16, 18), diphenylbutanol O-methylcatechol (17), recipavrin O-methylcatechol (19) and a secondary formamide (5) were identified by g.l.c.-mass spectrometry. 4. Various extraction solvents were employed in sample workup. The formamide (5) was present regardless of solvent used, while the trace presence of secondary acetamide (7) may be associated with the use of ethyl acetate. 5. Metabolites isolated after beta-glucuronidase hydrolysis were characterized by g.l.c.-mass spectrometry of the underivatized form, and as the trimethylsilyl (TMS) derivatives, or following methylation with diazomethane or trimethylanilinium hydroxide (TMAH).
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PMID:Identification of the biliary metabolites of (+/-)-3-dimethylamino-1,1-diphenylbutane HCl (recipavrin) in rats. 208 98

1. Three dogs were treated i.v. with cannabidiol (CBD) and urine collected at intervals to 30 h. 2. Metabolites were extracted, converted into trimethylsilyl (TMS) derivatives and examined by g.l.c.-mass spectrometry. 3. The major metabolites excreted at early times were identified as the phenol glucosides of 4"-hydroxy-CBD, 5"-hydroxy-CBD and 6-oxo-CBD. 4. These three oxidized metabolites were not found unconjugated, and none of the free oxidized metabolites in urine were found conjugated with glucose. 5. The conjugates were hydrolysed by beta-glucuronidase Type HP-2 from Helix pomatia and acid phosphatase but not by beta-glucuronidase Type VII from E. coli. Differential reactivity towards alpha- and beta-glucosidase indicated that they possessed the beta-configuration.
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PMID:Identification of glucose conjugates as major urinary metabolites of cannabidiol in the dog. 233 14

The metabolism of benzo(a)pyrene [B(a)P] to organic soluble and water soluble metabolites by transformable C3H10T1/2CL8 mouse embryo fibroblasts was studied as a function of time, B(a)P concentration, and cell density. The total formation of organic-soluble and water-soluble metabolites increased with incubation time from 4 to 48 h and with B(a)P concentration from 4 to 40 microM. As cell density increased, the metabolic rate decreased for organic-soluble and water-soluble products between 6,300 and 54,000 cells/cm2 probably due to decreases in B(a)P concentrations to values below saturation. Specific organic-soluble metabolites identified were B(a)P-pre-9,10-diols, B(a)P-9,10-diol, B(a)P-7,8-diol, B(a)P-3,6-quinone, B(a)P-3-phenol, and B(a)P-9-phenol. Water-soluble metabolites were subjected to enzymatic hydrolysis with beta-glucuronidase and aryl sulfatase to identify specific conjugated products. The sulfate conjugated metabolites identified were B(a)P-7,8-diol, B(a)P-pre-9,10-diols, B(a)P-9,10-diol, and B(a)P-3,6-quinone. The beta-glucuronic acid metabolites identified were B(a)P-pre-9,10-diols, B(a)P-3,6-quinone, and B(a)P-3-phenol. Patterns of metabolite formation rates are discussed as to their possible effect on morphological transformation rates in C3H10T1/2 cells with respect to incubation time and cell density.
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PMID:Quantitative analysis of the metabolism of benzo(a)pyrene by transformable C3H10T1/2CL8 mouse embryo fibroblasts. 287 41

A large proportion of the metabolites formed from benzo[a]pyrene (BP) in cell cultures from rodents, fish and humans result from conjugation of an oxidized metabolite of BP with sulfate, glucuronic acid or glutathione (GSH). To improve the analysis of these metabolites, a reversed-phase ion-pair h.p.l.c. system using a step gradient of methanol:tetrabutyl-ammonium bromide in ammonium formate buffer has been developed for the separation of these three classes of conjugates. This system separated 3-hydroxy-BP glucuronide and sulfate conjugates and resolved them from GSH conjugates of BP 4,5-oxide, 7,8-oxide and 7,8-diol-9,10-epoxide. Cultures of early passage Syrian hamster, Wistar rat and Sencar mouse embryo cells, a bluegill fry (BF-2) cell line and a human hepatoma cell line (HepG2) were exposed to [3H]BP for 24 h. Medium samples from each were extracted with chloroform: methanol:water, and the water-soluble metabolites were analyzed by ion-pair h.p.l.c. The largest peak of metabolites in the media from cell cultures from rodents and the bluegill fry cell line co-eluted with the glucuronic acid conjugate of 3-hydroxy-BP. These phenol-glucuronides represented 48-62% of the total water-soluble metabolites in the fish and rodent cell cultures. Treatment of this material with beta-glucuronidase released 3-hydroxy-BP and 9-hydroxy-BP in ratios from 3:4 to 13.3:1 in various cultures. Media from the bluegill fry cell line and the mouse embryo cell cultures also contained a peak of BP-diol glucuronides; treatment of these peaks with beta-glucuronidase released mainly BP-7,8-diol. In HepG2 cells, 40% of the water-soluble metabolites were identified as sulfate conjugates of 3-hydroxy-BP and 9-hydroxy-BP. No glucuronic acid conjugates of BP metabolites were detected in HepG2 cells. Only small amounts of the water-soluble metabolites from these cell cultures eluted in the same volumes as the synthetic GSH conjugate of BP-4,5-oxide, BP-7,8-oxide and BP-7,8-diol-9,10-oxide. These studies indicate that conjugation with glucuronic acid represents a major pathway of formation of water-soluble metabolites from BP in cells derived from a number of species and demonstrate the value of this ion-pair h.p.l.c. system for the analysis of conjugates formed from BP.
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PMID:Separation by ion-pair high-performance liquid chromatography of the glucuronide, sulfate and glutathione conjugates formed from benzo[a]pyrene in cell cultures from rodents, fish and humans. 380 96

The effect of sodium taurocholate on the biliary export of stable mutagenic phenolic glucuronide metabolites of benzo(a)pyrene from livers of corn oil- or 3-methylcholanthrene-treated rats was studied using a nonrecirculating perfusion system. Sterile bile samples were collected every 4 min and assayed for mutagens using the Ames Salmonella (Ta 98) test without addition of microsomes but containing beta-glucuronidase. Rates of export of mutagens produced from benzo(a)pyrene (20 microM) into the bile were stimulated 5-fold by the bile salt sodium taurocholate, concomitant with a 2- to 3-fold increase in bile flow. Steady-state rates of 60 and 90 revertants/g/h were observed in bile when 20 microM benzo(a)pyrene was infused into livers from corn oil or 3-methylcholanthrene-treated rats, respectively. These rates of efflux were increased to 250 and 550 revertants/g/h by the addition of taurocholate. Rates of production of mutagenic phenolic metabolites which account for the mutagenic activity were determined by adding rates of efflux into bile and effluent perfusate with rates of accumulation of metabolites in the cell. In livers from 3-methylcholanthrene-treated rats, rates (8 min) of benzo(a)pyrene phenol formation averaged 300 nmol/g/h during the initial 20 min of perfusion but increased to 450 nmol/g/h after 1 h. The addition of taurocholate increased maximal rates of phenol efflux in the bile from 6 to 148 nmol/g/h and decreased rates of phenol accumulation in intracellular stores from 342 to 220. Rates of efflux into the vena cava effluent averaged 120 nmol/g/h and were not affected by taurocholate. Infusion of dehydrotaurocholate increased the appearance of metabolites of benzo(a)pyrene in the effluent perfusate but did not change rates of efflux into bile. Taurocholate doubled rates of output of phenolic metabolites into the effluent perfusate when bile flow was arrested by perfusion with calcium-free buffer. Thus, mutagenic glucuronides from benzo(a)pyrene phenols accumulated in hepatocytes much faster than rates at which they were exported. Total rates of production of phenolic glucuronides by the liver were not affected by bile salts; however, taurocholate stimulated their export into bile, while dehydrotaurocholate increased their concentration in the effluent perfusate. Both salts probably act by displacing metabolites from intracellular binding sites.
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PMID:Effect of bile salts on rates of formation, accumulation, and export of mutagenic metabolites from benzo(a)pyrene produced by the perfused rat liver. 397 30

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


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