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)

Heparan sulfate (HS), a prominent component of vascular endothelial basal lamina, is cleaved into large Mr fragments and solubilized from subendothelial basal lamina-like matrix by metastatic murine B16 melanoma cells. We have examined the degradation products of HS and other purified glycosaminoglycans produced by B16 cells. Glycosaminoglycans 3H-labeled at their reducing termini or metabolically labeled with [35S]sulfate were incubated with B16 cell extracts in the absence or presence of D-saccharic acid 1,4-lactone, a potent exo-beta-glucuronidase inhibitor, and glycosaminoglycan fragments were analyzed by high speed gel permeation chromatography. HS isolated from bovine lung, Engelbreth-Holm-Swarm sarcoma, and subendothelial matrix were degraded into fragments of characteristic Mr, in contrast to hyaluronic acid, chondroitin 6-sulfate, chondroitin 4-sulfate, dermatan sulfate, keratan sulfate, and heparin which were essentially undegraded. Heparin, but not other glycosaminoglycans, inhibited HS degradation. The time dependence of HS degradation into particular Mr fragments indicated that HS was cleaved at specific intrachain sites. In order to determine specific HS cleavage points, HS prereduced with NaBH4 was incubated with a B16 cell extract and HS fragments were separated. The newly formed reducing termini of HS fragments were then reduced with NaB[3H]4, and the fragments hydrolyzed to monosaccharides by trifluoroacetic acid treatment and nitrous acid deamination. Since 3H-reduced terminal monosaccharides from HS fragments were overwhelmingly (greater than 90%) L-gulonic acid, the HS-degrading enzyme responsible is an endoglucuronidase (heparanase).
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PMID:Metastatic melanoma cell heparanase. Characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase. 669 65

We studied thyroid hormone (TH) conjugation in fasted trout by incubating isolated hepatocytes with either [125I]T4 or [125I]T3, and by analyzing bile from trout injected with either [125I]T4 or [125I]T3. Glucuronide conjugates were identified by hydrolysis with beta-glucuronidase and sulfate conjugates by acid solvolysis with ethyl acetate/trifluoroacetic acid (1%). We used Sephadex LH-20 chromatography to concentrate the conjugate fractions from hepatocyte incubates prior to HPLC analysis. Glucuronide conjugates of T4 and T3 were produced in vitro and glucuronides of T4, T3, and 3,3'-T2 were found in vivo. Sulfation of T4 occurred in vitro and in vivo. T3 sulfation was not established in vitro, but sulfate conjugates of T3 and T2 were found in bile. Significant proportions of unconjugated T4 and T3 also occurred in the bile. We conclude that (i) as in other vertebrates, iodothyronines undergo hepatic glucuronidation and are excreted as such in the bile, (ii) T4 and T3 undergo sulfation, and in contrast to mammals, are excreted in significant amounts in the bile, (iii) 3,3'-T2, a prominent deiodination product of T3, is excreted as both glucuronide and sulfate conjugates, and (iv) the isolated hepatocyte system is appropriate for studying aspects of TH metabolism in trout.
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PMID:Identification of thyroid hormone conjugates produced by isolated hepatocytes and excreted in bile of rainbow trout, Oncorhynchus mykiss. 881 56

The incorporation of eight benzodiazepines (chlordiazepoxide, diazepam, estazolam, flunitrazepam, flurazepam, medazepam, oxazepam and triazolam) into rat hair was investigated by HPLC and GC-MS. Each of the benzodiazepines was injected daily into three Dark Agouti (DA) rats for 10 days at 10mg/kg. The back hair of the rats was removed by shaving prior to the first injection and again on the 28th day after the initial administration. To investigate optimum extraction conditions, 10mg aliquots of rat hair incorporated with diazepam, flurazepam or medazepam were extracted by seven different methods (Proteinase K, methanol-ammonia, methanol-trifluoroacetic acid, Soerensens buffer, 1M NaOH, beta-glucuronidase/arylsulfatase, Biopurase). The method found to yield the highest recoveries, for all three drugs, was the acidic methanol extraction. Using this extraction procedure, the incorporation rates (ICR: the ratio of the hair concentration to the plasma AUC) of eight benzodiazepines into rat hair were investigated. The ICRs ranged from 0.002 (flunitrazepam) to 0.049 (flurazepam). The major metabolites of flurazepam were investigated in rat hair. The mean hair concentrations of desalkylflurazepam and 2-hydroxyethylflurazepam were 3.31 and 0.05 ng/mg, respectively, which are 24 and 0.36% of the parent compound in hair.
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PMID:A study into the rate of incorporation of eight benzodiazepines into rat hair. 1274 89

Taxifolin has been widely used in the treatment of cerebral infarction and sequelae, cerebral thrombus, coronary heart disease and angina pectoris. A reliable sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method with UV detection for the pharmacokinetic study of taxifolin in rabbit plasma after enzymatic hydrolysis was developed and validated for the first time. Taxifolin, with biochanin A as the internal standard, was extracted from plasma samples by liquid/liquid extraction after hydrolysis with beta-glucuronidase and sulfatase. Chromatographic separation was conducted on a Luna C18 column (4.6 mm x 150 mm, 5 microm particle size) and pre-column (2.0 mm, the same sorbent). Two-step linear gradient elution with acetonitrile and 0.03% water solution of trifluoroacetic acid as mobile phase at a flow rate of 1.0 ml/min was used. The UV detector is set at 290 nm. The elution time for taxifolin and biochanin A was approximately 7.9 and 18.3 min, respectively. The calibration curve of taxifolin was linear (r > 0.9997) over the range of 0.03-5.0 microg/ml in rabbit plasma. The limit of detection (LOD) and limit of quantification (LOQ) for taxifolin were 0.03 and 0.11 microg/ml, respectively. The present method was successfully applied for the estimation of the pharmacokinetic parameters of taxifolin following intravenous and oral administration of lipid solution to rabbits. The absolute bioavailability of taxifolin after oral administration of lipid solution was 36%.
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PMID:Determination and pharmacokinetic study of taxifolin in rabbit plasma by high-performance liquid chromatography. 1911 Apr 6