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

---

Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biotransformation of croconazole, a potent new antimycotic agent, was studied in the rabbit. Croconazole was excreted in the urine primarily as conjugates. Most of the radioactive metabolites in the urine could be extracted with organic solvent after hydrolysis with beta-glucuronidase. As many as 16 metabolites in the organic extracts were separated by TLC. Thirteen were identified by comparison of their mass and/or proton NMR spectra with those of synthetic samples. Aromatic ring hydroxylation of each benzene ring, O-dechlorobenzylation, and loss of the imidazole ring were found to occur.
...
PMID:Metabolism of the antimycotic agent, croconazole, in rabbits. 256 15

The metabolism of an orally administered, 10-mg single dose of the antianxiety drug buspirone was studied in the rat. Samples of bile and urine were collected for 6 hr and were treated with beta-glucuronidase/arylsulfatase. The deconjugated metabolites were isolated and purified by HPLC. Structural analysis was carried out by combined gas chromatography/electron impact mass spectrometry as their trimethylsilyl derivatives and by 1H-NMR spectroscopy. Structures of the metabolites were further confirmed by co-elution on HPLC with authentic standards when possible. In addition to the already known metabolites 5-hydroxy-buspirone and 1-pyrimidinylpiperazine, seven major metabolites were unambiguously identified together with unchanged drug. Ten minor metabolites were partially characterized. Hydroxylation alpha to the glutaramidyl carbon at the 6'-position on the bicyclo ring system, hydroxylation on the pyrimidine aromatic ring, and N-dealkylation of the butyl side chain were observed as major routes of metabolism. Minor routes of metabolism observed were: 3'-hydroxylation on the bicyclo ring system and formation of the methylated catechol derivatives. The identified metabolites accounted for greater than 90% of the total metabolites excreted in the rat bile and urine samples.
...
PMID:Metabolism of the antianxiety drug buspirone in the rat. 257 98

The metabolism of an oral dose (20 mg) of the antianxiety drug buspirone labeled with 14C/15N was studied in human subjects. 15N was incorporated in the molecule to facilitate structural characterization of the metabolites by mass spectrometry. Urine samples were collected at intervals up to 24 hr and analyzed for radioactivity. Cumulative urinary excretion accounted for 50% of the dose in 24 hr. The urine was hydrolyzed with beta-glucuronidase/arylsulfatase and the deconjugated metabolites were isolated and purified by HPLC. The purified metabolites were identified by GC/MS, 1H-NMR, and comparison with authentic standards when available. Seven metabolites of buspirone were identified unambiguously, together with unchanged drug. Hydroxylation alpha to the glutarimidyl carbonyl at the 6'-position on the spiro ring system, hydroxylation at the 5-position on the pyrimidine ring, and N-dealkylation of the butyl-substituted side chain were major routes of metabolism. The identified metabolites accounted for 88% of the total radioactivity in the urine. A scheme for metabolism of buspirone in human subjects has been proposed.
...
PMID:Metabolism of the antianxiety drug buspirone in human subjects. 257 99

Thrombin stimulation of human platelets initiates a membrane depolarization attributable to a Na+ influx into, and an alkalinization of, the cytoplasm, both of which follow a similar rapid time scale and thrombin-dose dependence. These responses precede secretion of the contents of the dense granules (serotonin) and, after 1 minute, of lysosomes (beta-glucuronidase). We have evaluated these parameters in the presence of 2H2O in order to determine if the Na+ influx and H+ efflux are sequential or simultaneous. NMR evidence indicates that 2H2O equilibration in rapid, and virtually complete within the 3 min prestimulation platelet equilibration period. In response to an 0.05 U/ml addition of thrombin, the rate of depolarization is 70-80% slower in 2H2O than in H2O. The time to reach maximal depolarization is 5 to 10 seconds longer in 2H2O, the extent of depolarization 60% inhibited, and the pH change 85% inhibited. The serotonin secretion is unaltered, while the beta-glucuronidase secretion is 130-180% enhanced. Dimethylamiloride inhibits the Na+ influx and the pH change completely. These results suggest that the Na+ and H+ fluxes across the plasma membrane are interdependent but neither simultaneous nor electroneutral. Furthermore, granule secretion, previously shown by us to be independent of the existent Na+ gradient, depends on the cytoplasmic K+ and H+ concentrations.
...
PMID:Sequential sodium-proton exchange in thrombin-induced human platelets. 282 Apr 94

Metabolism of pantothenic acid (PaA) in beagle dogs was investigated. The dogs excreted 12.3% of the dose in the urine within 24 hr after a single oral administration of [3H]PaA (3 mg/kg). High performance liquid chromatographic analysis of the urine showed the presence of unchanged vitamin and a major metabolite, which accounted for 60.2 and 39.8% of the urinary radioactivity respectively. Although the metabolite was hydrolyzed by treatment with beta-glucuronidase or acid phosphatase, it was found that this hydrolysis resulted from the actions of beta-glucosidase contained as a contaminant in these enzyme preparations. beta-Glucosidase completely hydrolyzed the metabolite to generate PaA and glucose. The metabolite was isolated and subjected to GC/MS and NMR analyses. It was identical to synthetic PaA beta-glucoside, 4'-O-(beta-D-glucopyranosyl)-D-pantothenic acid. It was shown by the use of dog liver microsomes that PaA underwent beta-glucosidation in the presence of uridine diphosphate glucose (UDPG). It is proposed that beta-glucosidation by UDP-glucosyltransferase is a novel metabolic pathway of PaA in the dog.
...
PMID:Glucoside formation as a novel metabolic pathway of pantothenic acid in the dog. 309 35

The metabolic fate of 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), a carcinogen formed in cooked meat and fish, has been investigated in male Sprague-Dawley rats. Five metabolites were recovered from bile of animals given an intragastric dose of [2-14C]MeIQx. These accounted for nearly all of the radioactivity in bile. The chemical structures of these metabolites were elucidated by proton NMR, UV and mass spectroscopy. Three structures may be assigned unambiguously: two sulfamates, N-(3,8-dimethylimidazo [4,5-f]quinoxalin-2-yl)sulfamic acid and N-(8-hydroxy-methyl-3-methylimidazo[4,5-f]quinoxalin-2-yl) sulfamic acid, and one glucuronide, N2-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f ]quinoxaline. In addition, an acetyl and a glucosiduronyl conjugate of 5-hydroxy-MeIQx were observed. The spectral evidence did not allow an unambiguous assignment of the site of conjugation. The two glucuronides were excreted in urine and the sulfamate of MeIQx was found in feces as well as urine. All five metabolites were found to be non-mutagenic to Salmonella typhimurium TA98 with or without metabolic activation. The glucuronide conjugates were found also to be non-mutagenic when beta-glucuronidase was incorporated with S-9 mixture in the mutation assay, and thus all appear to be detoxification products. The previously reported metabolite, 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxaline which is mutagenic to Salmonella typhimurium TA98 with metabolic activation, was identified as a minor component in both urine and feces.
...
PMID:Major routes of metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the rat. 337 Jul 49

Four unconjugated metabolites, which were produced through the oxidation of the isopropyl chain of 2-isopropylnaphthalene (2-IPN), were isolated from the urine of rabbits receiving 2-IPN orally and identified: 2-(2-naphthyl)propionic acid, 2-(2-naphthyl)-2-propanol, 2-(2-naphthyl)-1,2-propanediol, and 2-(2-naphthyl)-2-hydroxypropionic acid, together with a small amount of the unchanged compound. Further, the unconjugated metabolites, which were produced through the oxidation of the naphthalene ring, were isolated and identified: 2-isopropylnaphthols and 2-isopropyl-5,6 (or 7,8)-dihydronaphthalene-5,6 (or 7,8)-diol. The identification of these metabolites was made by means of TLC, GLC, MS, IR, GC/MS, and FT-NMR. The presence of glucuronides of metabolites B, C, D, F, and H was also suggested by TLC and GLC of the extract obtained after hydrolysis by beta-glucuronidase. In addition, quantitative determination of the metabolites indicated that the total urinary excretion of the metabolites except 2-isopropylnaphthols in 24 hr after administration was about 29% of the dose.
...
PMID:Identification and determination of urinary metabolites of 2-isopropylnaphthalene in rabbits. 360 68

All-trans retinoyl fluoride reacts with the 3,6-lactone of glucuronic acid in slightly alkaline solution to give the lactone of retinoyl beta-glucuronide, along with other retinoyl glucurono-lactones, in about 60% yield. Hydrolysis of the lactone with very dilute alkali gives the free acid, retinoyl beta-glucuronide, in about 80% yield. Pure all-trans retinoyl beta-glucuronide (overall yield: 20-25%) was obtained free from other isomeric and anomeric forms by reverse-phase high pressure liquid chromatography. Retinoyl beta-glucuronide was characterized by UV-visible, infrared, and 1H-NMR spectra, by elementary analysis, by mass spectra, and by its susceptibility to hydrolysis by bacterial beta-glucuronidase.
...
PMID:Chemical synthesis of all-trans retinoyl beta-glucuronide. 390 6

For the antiinflammatory drug zomepirac (Z), 5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2 acetic acid, the glucuronic acid conjugate (ZG) is the major metabolite. During analytical development ZG was found to be unstable at physiological pH, leading to four compounds other than Z. ZG and the other fractions were purified from urine by preparative HPLC and the structure of ZG was confirmed by elemental analysis and by NMR and mass spectrometry. Fast atom bombardment mass spectrometry was used to analyze the unstable, underivatized acyl glucuronides. ZG was cleaved by beta-glucuronidase but the other fractions were not. The stability of ZG was determined over a pH range of 1-8; the half-life was 27 min at pH 7.4 and 37 degrees C in water; maximum stability was found at pH 2. Intramolecular acyl migration of the glucuronide is postulated, as four of the isolated fractions formed from ZG yielded a mass-spectral parent ion corresponding to ZG+ H. The importance of sample handling prior to analysis to avoid acyl migration is emphasized.
...
PMID:Apparent intramolecular acyl migration of zomepirac glucuronide. 612 95

Excretion of 3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid (I) and its metabolites was studied in rats, beagle dogs, and rhesus monkeys given 20-mg/kg doses of 14C-labeled drug. The urine of rhesus monkeys contained two metabolites in addition to unchanged drug. Both metabolites were hydrolyzed to I by beta-glucuronidase and the hydrolysis was inhibited by 1,4-saccharolactone, indicating that they were glucuronides of I. One of the metabolites (III) was not hydrolyzed by dilute alkali. Its NMR spectrum indicated that the site of conjugation was one of the nitrogen atoms, i.e., it was a quaternary N-glucuronide. The FAB mass spectrum was in conformity with this assignment. This metabolite was not present in the urine of dogs or rats given labeled drug. The other metabolite (II) was excreted in the urine of all three species as well as in the bile of the rat. It was readily hydrolyzed by dilute alkali (pH 11 for 0.5 hr at 37 degrees C), indicating that this metabolite was an acyl glucuronide. The metabolite was stable at pH 4.5 but it was readily converted to three isomers at 37 degrees C within 1 hr at pH 6.5 and above. The mass spectra of the derivatized isomers and metabolite were similar. The isomers were hydrolyzed to I by dilute alkali but not by beta-glucuronidase. They exhibited reducing properties (whereas metabolite II did not), suggesting that they were formed by acyl migration of the aglycone to the second, third, and fourth carbon atoms of the glucuronic acid moiety. Acyl migration probably plays a role in the disposition of I as well as other drugs that form labile glucuronides.
...
PMID:Metabolic formation of N- and O-glucuronides of 3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid. Rearrangement of the 1-o-acyl glucuronide. 613 Sep 7


<< Previous 1 2 3 4 5 6 7 Next >>

---