Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Urine from a dog dosed orally at 20 mg/kg with 14C-imirestat, a spirohydantoin aldose reductase inhibitor, contained 17.7 and 12.5% of the administered radioactivity at 0-48 and 48-72 h respectively. 2. Radio-h.p.l.c. of the 0-48 h urine revealed a complex mixture of metabolites and a small proportion of parent drug (1.6% of dose). Direct 19F-n.m.r. spectroscopy of this urine showed the fluoride ion, numerous metabolites which were predominantly glucuronide conjugates and, as a minor component, the parent drug. 3. After incubation with beta-glucuronidase the 0-48 h urine gave a 19F-n.m.r. spectrum showing fewer signals. This finding is consistent with aromatic ring hydroxylation followed by glucuronidation being the major metabolite pathways. 4. Deconjugated urine was analysed by proton-coupled 19F-n.m.r. and two-dimensional 19F-19F correlated spectroscopy. Results indicate that major components included three monohydroxy metabolites, a diphenol with both phenolic functions in the same ring, and a phenolic metabolite containing only one fluorine atom. 5. Semi-preparative h.p.l.c. of 0-48 h dog urine gave individual glucuronides isolated as mixtures of C-9 epimers. These fractions were hydrolysed and purified a second time by h.p.l.c. to give aglycones which were analysed by multi-nuclear n.m.r. and g.l.c.-mass spectrometry. The 3- and 4-hydroxy derivatives of imirestat were identified, as was the 2-hydroxy product obtained during or following defluorination. The other major aglycone was postulated to be the 3-fluoro-2-hydroxy metabolite. This represents a novel 'NIH-shift' type pathway for the metabolism of fluorobenzenes.
 ...
PMID:Application of 19F-n.m.r. spectroscopy to the identification of dog urinary metabolites of imirestat, a spirohydantoin aldose reductase inhibitor. 145

2-Fluoro-[6,7-3H]17 beta-oestradiol([3H]2-FE2) and 4-fluoro-[6,7-3H]17 beta-oestradiol([3H]4-FE2) were synthesized by the fluorination and reduction of [3H]oestrone and purified by HPLC. [3H]2-FE2 and [3H]4-FE2 (72.5 micrograms/kg; 0.25 mumol/kg) were administered i.v. to anaesthetized female and male Wistar rats (N = 4) with biliary cannulae. Bile was collected for 6 hr. Female rats administered [3H]2-FE2 excreted 85% of the dose into bile over 6 hr whilst male rats excreted 77%. After the administration of [3H]4-FE2, female and male rats excreted 72 and 83% of dose into bile over 6 hr, respectively. The biliary metabolites were glucuronides in all cases. The principal metabolite of [3H]2-FE2 liberated from biliary conjugates by beta-glucuronidase was 2-fluoroestrone in both female rats (64% of dose) and male rats (57%). No 2-hydroxylated, i.e. oxidatively defluorinated, metabolites were detected in either sex. In contrast, 2-hydroxylation of [3H]4-FE2 did occur, but only in female rats: 2-hydroxy-4-fluoro-oestrone (22%) and 2-methoxy-4-fluoroestrone (17%) were identified as biliary aglycones. However, the major metabolite was 4-fluoroestrone (4FE1; 38%). In male rats, 4-FE1 and 4-fluoro D-ring-oxygenated products were the principal biliary aglycones. The differences in metabolism between the two fluoro analogues and oestradiol are discussed with particular reference to the possible involvement of 2- and 4-hydroxy (catechol) oestrogens in oestrogen toxicity.
 ...
PMID:The metabolism of 2- and 4-fluoro-17 beta-oestradiol in the rat and its implications for oestrogen carcinogenesis. 155 97

Gas chromatography-negative-ion chemical ionization mass spectrometry (GC-NICI-MS) allowed the detection of extremely low plasma concentrations of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG). Glucuronide and sulphate conjugates of MHPG were determined after enzymatic hydrolysis of plasma with beta-glucuronidase-arylsulphatase. A 1-ml plasma sample was extracted at the pH of the hydrolysis (pH 4.8) with ethyl acetate, and the dry extract was derivatized with pentafluoropropionic anhydride in ethyl acetate. After evaporation of the solvent, the residue was dissolved in benzene and an aliquot was analysed by GC-NICI-MS. A trideuterated analogue of MHPG was used as an internal standard. Negative-ion chemical ionization of the pentafluoropropionyl derivatives was carried out using ammonia. The ion-molecule adducts at m/e 766 and 785 (MHPG) and m/e 769 and 788 (internal standard) were formed from the pentafluoropropionyl derivatives with the ions of m/e 163 (CF3CF2COO-) and m/e 144 (loss of fluorine from m/e 163). The concentrations of the ions of m/e 163 and 144 play a major role in the sensitivity and precision of this technique, which allows the detection of free MHPG plasma concentrations as low as 100 pg/ml in routine analysis.
 ...
PMID:Determination of low plasma concentrations of 3-methoxy-4-hydroxyphenylethylene glycol using gas chromatography-negative-ion chemical ionization mass spectrometry. 406 68

1: The use of fluorine-19 nuclear magnetic resonance (19F-NMR) and gas chromatography-electron capture detection (GC-ECD) in the analysis of fluorine-containing products in the urine of sevoflurane-exposed patients was explored. 2: Ten patients were anaesthetized by sevoflurane for 135-660 min at a flow rate of 6 l min(-1). Urine samples were collected before, directly after and 24 h after discontinuation of anaesthesia. 3: 19F-NMR analysis of the urines showed the presence of several fluorine-containing metabolites. The main oxidative metabolite, hexafluoroisopropanol (HFIP)-glucuronide, showed two strong quartet signals in the 19F-NMR spectrum. HFIP concentrations after beta-glucuronidase treatment were quantified by (19)F-nuclear magnetic resonance. Concentrations directly after and 24 h after discontinuation of anaesthesia were 131 +/- 41 (mean +/- SEM) and 61 +/- 19 mol mg(-1) creatinine, respectively. Urinary HFIP excretions correlated with sevoflurane exposure. 4: Longer scanning times enabled the measurement of signals from two compound A-derived metabolites, i.e. compound A mercapturic acid I (CAMA-I) and compound A mercapturic acid II (CAMA-II), as well as products from beta-lyase activation of the respective cysteine conjugates of compound A. The signals of the mercapturic acids, 3,3,3-trifluoro-2-(fluoromethoxy)-propanoic acid and 3,3,3-trifluorolactic acid were visible after combining and concentrating the patient urines. CAMA-I and -II excretions in patients were completed after 24 h. 5: Since 19F-nuclear magnetic resonance is not sensitive enough, urinary mercapturic acids concentrations were quantified by gas chromatography-electron capture detection. CAMA-I and -II urinary concentrations were 2.3 +/- 0.7 and 1.4 +/- 0.4 mol mg(-1) creatinine, respectively. Urinary excretion of CAMA-I showed a correlation with sevoflurane exposure, whereas CAMA-II did not. 6. The results show that 19F-nuclear magnetic resonance is a very selective and convenient technique to detect and quantify HFIP in non-concentrated human urine. 19F-nuclear magnetic resonance can also be used to monitor the oxidative biotransformation of sevoflurane in anaesthetized patients. Compound A-derived mercapturic acids and 3,3,3-trifluoro-2-(fluoromethoxy)-propanoic acid and 3,3,3-trifluorolactic acid, however, require more sensitive techniques such as gas chromatography-electron capture detection and/or gas chromatography-mass spectrometry for quantification.
 ...
PMID:Use of 19F-nuclear magnetic resonance and gas chromatography-electron capture detection in the quantitative analysis of fluorine-containing metabolites in urine of sevoflurane-anaesthetized patients. 1520 1