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. A radiochemical method for the studies on the microsomal UDPglucuronic acid metabolism has been developed. 2. The rat liver microsomes caused a rapid hydrolysis of UDPglucuronic acid to D-glucuronic acid 1-phosphate and further although much slower to free D-glucuronic acid. In Tris-HCl buffer (pH 7.4) they were produced in ratio 72 : 1. No other metabolites were found in measurable amounts. The pyrophosphatase splitting UDPglucuronic acid showed a pH optimum at 8.9, but the liberation of D-glucuronic acid from UDPglucuronic acid had two pH maxima (pH 3.5 and 8.5). EDTA appeared to be less powerful inhibitor of pyrophosphatase than previously suggested. About 25 per cent of the UDPglucuronic acid hydrolyzing activity was still remaining in the presence of 10 mM EDTA. D-Glucaro-1,4-lactone was found to have a slight inhibitory action on the pyrophosphatase activity. Citrate inhibited powerfully the hydrolysis of UDPglucuronic acid and the liberation of free D-glucuronic acid. Phosphate was also inhibitory. 3. In the presence of an exogenous UDPglucuronosyltransferase substrate, 4-nitrophenol, the formation of D-glucuronic acid 1-phosphate and free D-glucuronic acid were slightly reduced, and D-glucuronic acid 1-phosphate, 4-nitrophenylglucuronide and free D-glucuronic acid were produced in ratio 78 : 23 : 1. When 10 mM EDTA was added to diminish the hydrolytic consumption of the glucuronyl donor substrate, the corresponding ratio was still as unfavorable as 19 : 2.6 : 1. The measurable activity of UDPglucuronosyltransferase was lower in the presence of phosphate or citrate than in Tris-HCl buffer, although they protected the glucuronyl donor substrate against hydrolysis. 4. The results indicate that even in the presence of added glucuronyl acceptor substrate the hydrolysis of UDPglucuronic acid predominates the conjugation in rat liver microsomes. The rate of the hydrolysis of UDPglucuronic acid is quite considerable even in the presence of EDTA, and it is recommended to control the UDPglucuronic acid pyrophosphatase activity when UDPglucuronosyltransferase and glucuronidation reactions are studied. Free D-glucuronic acid appears to be produced from UDPglucuronic acid for further use via D-glucuronic acid 1-phosphate, the rate-limiting step being the hydrolysis of this intermediate. UDP-glucuronosyltransferase, glucuronides of either endogenous or exogenous aglycones and beta-glucuronidase have only a minor role in this respect in rat liver microsomes.
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PMID:Pyrophosphatase and glucuronosyltransferase in microsomal UDPglucuronic-acid metabolism in the rat liver. 0 Dec 76

The biological transformation of phenyramidol (I), some of which is also excreted unchanged, occurs by three main degradative pathways: 1. Hydroxylation of the pyridine ring in position 3 (metabolite V) and 5 (metabolite VI). 2. Cleavage of the ethanolamine chain with the formation of 2-aminopyridine (metabolite II) and presumably mandelic aldehyde. 3. Conjugation with glucuronic acid (metabolite III). Secondary reactions result in the production of: benzoyl carbinol (metabolite XV), benzoic acid (metabolite XI), mandelic acid (metabolite XII) and the glucuronides of V, VI, VII, XII and possibly II (metabolites VIII, IX, X, XIII and IV), all of which were also found as free, unconjugated compounds. A further, unusual reaction is the dimerisation of metabolite VI with the formation of a dipyridyl derivative (metabolite VII), which is excreted partly as the free compound, but mainly as the glucuronide (metabolite X). The occurrence of 2-(N-benzylamino)-pyridine (XIV) in the urine could not be explained. Four futher excretory products (metabolites XVI, XVII, XVIII and XIX) were not identified; XVI and XVII were extracted at an alkaline pH, whereas XVIII and XIX were extracted under neutral conditions. They could be detected both as free compounds, and after hydrolysis with HCl or alkali, but not after treatment with beta-glucuronidase.
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PMID:[Isolation and identification of some metabolites of phenyramidol (Cabral) from human urine (author's transl)]. 92 36

Urinary metabolites and biological half-life of chlorpyrifos (O, O-diethyl-O-3,5,6-trichloro-2-pyridinyl phosphorothioate) were investigated. Male Wistar rats weighing 200 g were intraperitoneally injected with chlorpyrifos at a level of 0.2 mmol/kg body weight. Both chlorpyrifos and 3,5,6-trichloro-2-pyridinol (TCP) levels in blood showed maximum values at 5 h post-injection, and then decreased rapidly. Biological half-lives of the blood chlorpyrifos and TCP were estimated to 8.15 and 24.66 h, respectively. Urine was collected for 96 h post-injection and hydrolyzed with 4 N HCl or beta-glucuronidase with sulfatase, and TCP released was determined. Urinary excretion levels of the acid hydrolysis-released TCP and the enzyme hydrolysis-released TCP accounted for 86 and 54% of chlorpyrifos administered, respectively. Urinary excretion levels of alkylphosphate for 96 h post-injection were analyzed. The excretion levels of diethylthiophosphate (DETP) and diethylphosphate (DEP) accounted for 45 and 15% of chlorpyrifos administered, respectively. These results indicate that 1) about half of the chlorpyrifos administered was directly hydrolyzed to DETP and TCP, 2) 10 to 20% was hydrolyzed to DEP and TCP after the oxidation to chlorpyrifos oxon, and 3) about 30% was dealkylated to TCP-phosphate after the oxidation.
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PMID:[Metabolism and urinary excretion of chlorpyrifos in rats]. 247 31

M-GTFI, originally screened as an inhibitor of Streptococcus mutans glucosyltransferase, strongly inhibited alpha-glucosidase, in a non-competitive manner especially when the synthetic substrate p-nitrophenyl-alpha-D-glucopyranoside was used. It also inhibited beta-glucosidase, beta-amylase and, to a lesser extent, beta-glucuronidase. The inhibitor was stable in neutral and alkaline pH ranges and dependency of the inhibition on pH and temperature was not observed. Some proteinases and polysaccharides-hydrolyzing enzymes as well as human saliva did not inactivate the inhibitor. There was a correlation between the release of sulfate anions from the inhibitor molecule on incubation with HCl (0.2 N) at 100 degrees C and loss of inhibitory properties of the molecule. It is suggested that the presence of sulfate ester linkages in the inhibitor molecule play an important role in the inhibition process.
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PMID:Characteristics of M-GTFI, a new inhibitor of Streptococcus mutans glucosyltransferase. 297 50

A liquid chromatographic (LC) method is described for the determination of the plant estrogens diadzein, formononetin, and coumestrol and the estrogenically active metabolite equol in bovine blood plasma and urine. The blood and urine samples are incubated overnight with and without beta-glucuronidase/sulfatase for analysis of both free and conjugated forms of estrogens. Samples are applied to Extrelut columns, extracted with ethyl acetate, and evaporated to dryness. Residues from urine samples are dissolved in methanol, diluted with water, acidified with HCl, and purified by injection through a Sep-Pak C18 cartridge. This eluate is used for LC analysis. Residues from blood samples are dissolved in benzene-petroleum ether (1 + 1), extracted with ammonium hydroxide, acidified with glacial acetic acid, and extracted with ethyl acetate. The ethyl acetate extract is evaporated, dissolved in 80% methanol, injected onto a LC reverse-phase column, and separated in a linear gradient system between 40 and 80% methanol in phosphate buffer. Quantitation is performed by means of UV and fluorescence responses. The method was sensitive enough to determine 0.4 ng/mL of daidzein and formononetin and 0.1 and 13 ng/mL of coumestrol and equol, respectively, in blood, and 130, 80, and 7 ng/mL of daidzein, formononetin, and coumestrol, respectively, and 4 micrograms/mL of equol in urine. The applicability of the method was checked by the determination of total and free plant estrogens in blood samples from a dairy cow fed a normal diet.
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PMID:Liquid chromatographic determination of the estrogens daidzein, formononetin, coumestrol, and equol in bovine blood plasma and urine. 323 13

The aim of these two studies was to evaluate the safety and pharmacokinetics of oral nalmefene, a new orally effective opioid antagonist. In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double-blind fashion to four groups of healthy men. There were six subjects in each group; four received nalmefene and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, such as lightheadedness, at the higher doses. Model-independent pharmacokinetic analysis of the plasma concentration-time data showed that nalmefene was rapidly absorbed and had an elimination half-life that ranged from seven to 15 hours (mean, 10.7 hr). There was a good linear relationship (r = .97) between administered dose and total area under the curve at each dose level. Only about 4% of the dose was excreted in the urine as unchanged nalmefene, whereas up to 60% was excreted as a beta-glucuronidase/sulfatase hydrolysable conjugate(s) of nalmefene. In the second study, six healthy men were initially administered a single 50-mg dose of drug, and plasma samples were obtained at selected time intervals for 48 hours. A dosing schedule of 20 mg q12h was then started and continued for seven days. Plasma samples were collected immediately before each dose and at selected times for up to 48 hours after the last dose. The drug was well tolerated by all subjects, and no clinically significant adverse effects were observed during the seven-day administration period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist. 368 May 80

Male Wistar rats were exposed to 1000 ppm n-hexane, and the excreted urinary metabolites were analyzed by capillary gas chromatography-mass spectrometry (GC-MS). 1-Hexanol, 2-hexanol, 3-hexanol, 2-hexanone, 2,5-hexanedione, 2,5-dimethyltetrahydrofuran, 2,5-dimethyl-2,3-dihydrofuran and gamma-valerolactone were identified by their retention times and their mass spectra. Quantitative gas chromatographic analyses were performed using an FID. Experiments on the hydrolysis of conjugated n-hexane metabolites revealed that enzymatic hydrolysis (in addition to acid hydrolysis) was not required, as treatment with HCl hydrolyzed conjugates sensitive to acid as well as conjugates sensitive to beta-glucuronidase. By incorporating acid hydrolysis only and by using C18-cartridges for sample extraction, a method was developed that allowed the determination of n-hexane metabolites with a sample preparation time of only 45 min. Assay precision was assessed by repeated analyses of the same urine sample. Coefficients of variation for the individual metabolites ranged from between 1.8 and 3.3.
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PMID:Methodological investigations on the determination of n-hexane metabolites in urine. 394 99

The plasma pharmacokinetics of the antineoplastic anthracycline antibiotic aclacinomycin A (Acm) and its metabolites were studied in 12 patients treated with 60-120 mg/m2 during a phase I clinical trial. Total plasma drug fluorescence initially declined very rapidly, but from 2 to 24 h after injection, fluorescence rose progressively to intensities greater than those measured 1 min after Acm injection. Plasma total drug fluorescence slowly declined from 24 to 72 hours after Acm administration. These events reflected the rapid disappearance of Acm and the subsequent appearance of two highly fluorescent metabolites. One metabolite co-chromatographed with and had a fluorescence spectrum identical to known metabolite F1 (bisanhydroaklavinone). The other metabolite did not co-chromatograph with any previously described Acm metabolite. This metabolite had a fluorescence spectrum unlike any previously described Acm metabolite and was not altered by treatment for 60 min with 0.2 N HCl at 100 degrees C or by treatment for 24 h at 37 degrees C with bacterial beta-glucuronidase or limpet aryl sulfatase.
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PMID:Plasma kinetics of aclacinomycin A and its major metabolites in man. 695 15

A sensitive and reliable assay for uridine 5'-diphosphoglucuronic acid (UDPGA) was developed that involved conjugation of diethylstilbestrol (DES) in vitro. This conjugation reaction is solely dependent upon UDPGA concentration. The assay uses 0.13 M Tris-HCl, pH 7.4, 6.7 mM MgCl2, 0.05% Brig 58, 0.25 mg guinea pig liver microsomal protein, 0.13 mM 3H-DES (0.2 microCi/ml), and 200 microliters of boiled 10% liver homogenate in a total volume of 0.5 ml. After a 60-min incubation at 37 degrees C, unconjugated DES is extracted into 5 ml of chloroform and the residual metabolized 3H-DES in the aqueous phase is determined by liquid scintillation spectrometry. After addition of beta-glucuronidase to the aqueous phase, about 90% of the radioactivity could be extracted into chloroform, demonstrating the DES-glucuronic acid is the primary metabolite. Thus, this method easily permits quantitation of UDPGA in rat liver in the 1-10 nmol range.
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PMID:Determination of hepatic uridine 5'-diphosphoglucuronic acid concentration by conjugation with diethylstilbestrol. 709 97

The urinary aldosterone (ALD) was measured by aldosterone RIA kit and the following results were obtained. (1) We have known that ten percent solution of bovine serum albumin (BSA) instead of free serum LAD is used as the diluent of the urine in aldosterone RIA kit. (2) The upper limits of free ALD, HCl-ALD and beta-glucuronidase ALD in the urine diluted with 10% BSA were 1.6, 9.0 and 9.5 micrograms/dl respectively. (3) The values of urinary conjugated HCl-ALD and beta-glucuronidase ALD were approximately 3.5 times and 4 times as much as that of free ALD respectively. (4) A good correlation was obtained among the results of three methods (HCl-ALD, beta-glucuronidase ALD and free ALD). (5) No difference was found in the values of the urinary ALD in the healthy subjects and the patients with essential hypertension, kidney diseases and acute liver diseases.
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PMID:[Estimation of the urinary aldosterone (author's transl)]. 732 22


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