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)

Since the biotransformation of paracetamol (Acetaminophen) is practically confined to conjugation, the quantitative determination of paracetamol excretion may provide important information on phase II of the drug metabolism. We elaborated a simple and rapid liquid chromatographic method for the assessment of paracetamol and its conjugated metabolites in the urine to be available for routine use in the clinicopharmacological laboratory. The persons involved in the trial were administrated 500 mg of paracetamol to be taken on an empty stomach in the morning. Subsequently, their urine was collected for 8 hours. The so-called free paracetamol of unchanged form excreted into the urine was measured from this 0 to 8 hours' urine fraction, then, after treating it with beta-glucuronidase/arysulphatase enzyme, the total amount of paracetamol released from the conjugate, as well as that of the existing free paracetamol, the so-called total paracetamol were determined. The urine extracts containing paracetamol obtained by ethylacetate, at pH 10, and dried under nitrogen stream were analysed by HPLC on an ODS column in an eluent of methanol and water mixture (3:7, v/v) in the presence of 3-acetaminophenol internal standard. The flow rate was 1 ml/min, the detection wavelength was 254 nm.
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PMID:[Determination of paracetamol in urine by liquid chromatography]. 223 43

A method for the preparation of calibration curves for acetaminophen glucuronide (NAPAG) and acetaminophen sulfate (NAPAS) in rabbit urine without use of authentic compounds in high-performance liquid chromatography was examined. Rabbits were dosed intravenously with acetaminophen (NAPA, 30 mg/kg). Urine was collected and diluted. A plot of the peak area ratio of NAPAG to internal standard against NAPA concentration after the hydrolysis of diluted urine with beta-glucuronidase was linear and passed through the origin. A linear tendency was also observed in the plot of the peak area ratio of NAPAS to internal standard against NAPA concentration calculated by the difference between the peak area ratio of NAPA after the hydrolysis with beta-glucuronidase and that with beta-glucuronidase/arylsulfatase. Thus, once the calibration curve has been prepared following the enzyme hydrolysis of NAPAG and NAPAS, then the concentration of NAPAG and NAPAS in the sample solution can be calculated from the peak of NAPAG and NAPAS, respectively. The method is simple, and has the advantage that pure standards of the individual NAPA metabolites are not required.
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PMID:A method for the preparation of calibration curves for acetaminophen glucuronide and acetaminophen sulfate in rabbit urine without use of authentic compounds in high-performance liquid chromatography. 344 75

Renal cytochrome P-450 levels, metabolism of acetaminophen (APAP) and aminopyrine, and activities of several phase II-associated enzymes [UDPGT, beta-glucuronidase, and glutathione-S-transferase (GST)] were determined in sedentary and exercised young and middle-aged Fischer-344 male rats. After an 8-week exercise regimen consisting of treadmill running at a moderate intensity, renal microsomal cytochrome P-450 levels were increased 60% and 37% in young and middle-aged runners, respectively. Exercise was found to increase renal deacetylation of APAP to the nephrotoxic metabolite p-aminophenol by 54% in young and 26% in middle-aged rats. Aminopyrine N-demethylase activity was increased 97% in the young runners only. In contrast, UDPGT, beta-glucuronidase, and GST activities were unchanged by treadmill running. NADPH-cytochrome c reductase activity, determined in young animals only, was also unaltered by exercise. Advanced age decreased renal cortical cytochrome P-450 content by 34% while having no effect on p-aminophenol production. Aminopyrine N-demethylase activity was increased by 130% with increased age. The only phase II-associated enzyme altered by age was GST activity, as sedentary middle-aged animals exhibited a 43% decrease in activity when compared with young rats. Young exercised rats did not gain weight as rapidly as sedentary rats, and middle-aged rats had a slight loss in weight during exercise. Moreover, running resulted in 30-36% less food consumption during the experimental period. In conclusion, this study demonstrated that exercise increased renal phase I drug metabolism without influencing phase II processes; furthermore, a substrate-specific modification of the response to exercise was observed in the aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased renal drug metabolism in treadmill-exercised Fischer-344 male rats. 810 May 4

Oxycodone (OCOD) and its metabolites, including oxymorphone (OMOR), noroxycodone (NOCOD) and noroxymorphone (NOMOR), are opioids that carry an OH group at position 14. Using capillary electrophoresis (CE) with a binary phosphate buffer containing 60% ethylene glycol (pH 7.9), the migration order of OCOD and OMOR with respect to their N-demethylated analogs was found to be reversed compared to that observed for codeine, dihydrocodeine, morphine and dihydromorphine, compounds that do not have an OH group at position 14. OCOD and structurally related compounds can also be distinguished from these opioids by their absorbance spectra at low wavelengths and via a characteristic neutral H2O loss at the MS2 level. Using the binary phosphate buffer, CE with UV detection is shown to be capable of monitoring OCOD, NOCOD, OMOR (after hydrolysis only) and NOMOR (after hydrolysis and in patient urine only) in alkaline liquid-liquid extracts of urines that were collected after ingestion of 10 mg OCOD hydrochloride and in a patient urine collected at steady state (80 mg OCOD hydrochloride daily). Using an aqueous pH 9 ammonium acetate buffer, these results were confirmed by CE-MS3. Based on CE-MS, MS2 and MS3 data, the absorbance spectra measured across the CE peaks and the relative position within the electropherogram, two peaks monitored in the UV absorbance electropherograms could be assigned to the two keto-reduced metabolites 6oxycodol (60COL) and nor6oxycodol, for which no standards were available. Comparison of data obtained with urines pretreated with two different enzyme products (beta-glucuronidase and beta-glucuronidase/arylsulfatase) suggest that OCOD, NOCOD and 6OCOL are mainly glucuronidated, whereas OMOR mainly forms other conjugates. Furthermore, in a first attempt to directly measure conjugates of the compounds of interest, solid-phase extracts were analyzed by CE-MS4, which revealed the presence of the acyl glucuronides of 6OCOL and OMOR and an unidentified OMOR conjugate. The quantitation of free OCOD and NOCOD by CE-MS using deuterated internal standards is also discussed briefly.
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PMID:Capillary electrophoresis and capillary electrophoresis-ion trap multiple-stage mass spectrometry for the differentiation and identification of oxycodone and its major metabolites in human urine. 1201 27