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 epithelium of caput and cauda epididymidis of the rat was studied with transmission electron microscopy (TEM) and freeze-fracture techniques. In thin sections of both zones, the tissue consisted mainly of tall columnar cells (principal cells) with long sterocilia. Clusters of small membrane-bound vesicles were located in the lumen between or immediately over the stereocilia. Freeze-fracture replicas also displayed groups of smooth-surface vesicles in the same location. Membrane-bound vesicles isolated from the lumen of the rat epididymis were studied by TEM. In thin sections, some of them contained an electron dense material and others looked empty. In addition, the hydrolases: beta-galactosidase, N-acetyl-glycosaminidase, alpha-mannosidase, aryl-sulfatase and beta-glucuronidase were detectable in pellets of vesicles treated with Triton X-100. The results presented here indicate the presence of membrane-bound vesicles observed by two different methodologies in the rat epididymal fluid and demonstrate five glycosidases in their content.
...
PMID:Morphological and enzymatic study of membrane-bound vesicles from the lumen of the rat epididymis. 775 84

Mouse colon adenocarcinoma Co38 is widely used as a screening model for human colon tumors. To understand better the influence of tumor size on the main drug-metabolizing enzyme systems, we tested 15 mouse Co38 tumors at different sizes. The average weight was 917 +/- 444 mg (range, 300-1,400 mg). Cytochromes P-450 (1A1/1A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase (EH), and glutathione-S-transferases (GST-alpha, -mu, and -pi) were assayed by immunoblotting. The activities of the following enzymes or cofactors were determined by spectrophotometric or fluorometric assays: 1-chloro-2,4-dinitrobenzene-GST (CDNB-GST), selenium-independent glutathione peroxidase (GPX), 3,4-dichloronitrobenzene-GST (DCNB-GST), ethacrynic acid-GST (EA-GST), total glutathione (GSH), uridine diphosphate-glucuronosyltransferase (UDP-GT), beta-glucuronidase (beta G), sulfotransferase (ST), and sulfatase (S). Our results showed the absence of all probed P-450s and EH in Co38 tumors. No relationship was found between the Co38 tumor weights and GPX, GST-alpha, and EA-GST (regression analysis). However, a significant correlation was found between the tumor weights and all other enzymes investigated. For certain enzymes or cofactors, a linear decrease (P < 0.05) was observed as a function of tumor weight (CDNB-GST, DCNB-GST, GST-mu, GST-pi, GSH, and beta G). Other enzymatic activities (UDP-GT, S, and ST) were found to decrease in medium-size tumors and to increase in large tumors (P < 0.05; quadratic correlation). These data demonstrate that the expression of many drug-metabolizing enzyme systems is altered during tumor growth and suggest that tumoral response to chemotherapy could be altered as a function of tumor size.
...
PMID:Influence of tumor size on the main drug-metabolizing enzyme systems in mouse colon adenocarcinoma Co38. 792 60

Following subcutaneous administration of [3H]chloramphenicol (CP) to duck, HPLC and TLC analyses showed that the two most important metabolites in 0- to 24-hr excreta were CP-oxamic acid and CP-alcohol, which together accounted for about one-third of the radioactivity therein. The remainder was due to unchanged CP (15% dose), CP-base (5% dose), and various metabolites representing < 4% dose each. Among these, CP-glucuronide and CP-sulfate have been previously isolated in mammals. In addition to these metabolites, several previously unreported in vivo CP biotransformation products were identified in this study by HPLC and MS comparison with synthetic reference compounds. These new metabolites were unequivocally identified as 1-O-monoacetyl CP, CP-1,3-diacetate, N-acetyl CP-base, CP-oxamylglycine, and CP-oxamylethanolamine. Besides these formally identified compounds, the CP-phosphate structure was tentatively assigned to a conjugate metabolite resistant to beta-glucuronidase and sulfatase hydrolysis. The possible origin of these metabolites is discussed extensively.
...
PMID:Evidence for new metabolic pathways of chloramphenicol in the duck. 795 33

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance has been mostly studied in vitro. In an attempt to better understand BCNU resistance in the in vivo situation, we compared the principal drug-metabolizing enzyme systems in two L1210 leukemia lines, one sensitive and one resistant to BCNU (L1210/BCNU), passaged in vivo in mice. The following enzymes were assayed by immunoblotting: cytochromes P-450 (1A1/1A2, 2B1/2B2, 2C8-10, 2E1, 3A), epoxide hydrolase (EH) and glutathione S-transferase (GST-alpha, -mu and -pi). The following enzymes and cofactors were assayed fluorometrically or spectrophotometrically: 1-chloro-2-4 dinitrobenzene-GST (CDNB-GST), total glutathione (GSH), UDP-glucuronosyltransferase, beta-glucuronidase, sulfatase and sulfotransferase. Results showed that cytochrome P-450 1A1/1A2 was the only isoenzyme detected in both L1210 and L1210/BCNU. CDNB-GST activity was significantly higher in L1210/BCNU compared with L1210. The isoenzyme GST-alpha was more abundant in L1210/BCNU compared with L1210, whereas GST-pi was expressed less in the BCNU-resistant leukemia line. GST-mu was not detected in either L1210 leukemia lines. GSH levels were similar in the two L1210 lines. No significant difference was observed between the two leukemia lines for the conjugative enzymes UDP-glucuronosyltransferase and sulfotransferase, whereas their corresponding hydrolytic enzymes beta-glucuronidase and sulfatase were about two-fold lower in the BCNU-resistant leukemia line. Epoxide hydrolase was 1.3-fold higher in L1210/BCNU compared with L1210 and this level was about three-fold higher than in mouse liver. In conclusion, these studies showed the presence of cytochrome P-450 1A1/1A2 in the two L1210 leukemia lines studied, and indicated noteworthy differences between the two leukemia lines for many enzyme systems such as GST, beta-glucuronidase, sulfatase and epoxide hydrolase. These data are of importance to better understand the mechanisms of drug resistance to nitrosoureas in vivo.
...
PMID:Principal drug-metabolizing enzyme systems in L1210 leukemia sensitive or resistant to BCNU in vivo. 796 9

The characterization and properties of a beta-galactanase and alpha- and beta-galactosidases as well as heparan sulfate and chondroitin sulfate degrading enzymes which appear during the 15 days of the embryonic development of the mollusc Pomacea sp. is reported. The beta-galactanase, which appears around day 7 of development, was separated from alpha- and beta-galactosidase which emerge at day 1 and 4 after oviposition, respectively. The galactanase seems to be responsible for the degradation of an acidic beta-galactan (which is also synthesized by the eggs around day 5) to galactose and di- and tri-galactosides. Heparan sulfate appears around day 10 of development together with a heparan sulfate endoglucuronidase responsible for the degradation of its N-acetylated region. An alpha-N-acetylglucosaminidase and a beta-glucuronidase which act upon the N-acetylated fragments formed from heparan sulfate emerge around day 4 of development. Chondroitin sulfate and a chondroitin sulfate sulfatase emerge around day 9 of development whereas a beta-N-acetylgalactosaminidase and the beta beta-galactan, heparan and chondroitin sulfate, respectively. The possible role of these elements in the migration of mesenchymal cells, in the processes of cell-cell recognition and control of cell growth is discussed.
...
PMID:Appearance and fate of a beta-galactanase, alpha, beta-galactosidases, heparan sulfate and chondroitin sulfate degrading enzymes during embryonic development of the mollusc Pomacea sp. 806 9

Fumonisin B1 (FB1) and fumonisin B2 (FB2) were determined in milk by liquid chromatography (LC) following immunoaffinity column cleanup. Recoveries from milk spiked with 5-50 ng each fumonisin/ml averaged 79-109%. The aminopentol hydrolysis product of FB1 (AP1) was determined by LC after cleanup on a C18 solid phase phase extraction column; mean recoveries were 69-83% at spiking levels of 50-100 ng AP1/ml milk. Detection limits were of the order 3-7 ng/ml for FB1 and FB2, and 20-25 ng/ml for AP1. A stability study showed no losses of FB1 and FB2 in milk under conditions of freezing, refrigeration and boiling. A transmission study using four cows dosed with pure FB1 either orally (1.0 and 5.0 mg FB1/kg b.w.) or by i.v. injection (0.05 and 0.20 mg FB1/kg b.w.) showed no detectable residues of FB1 or AP1 in the milk, with or without hydrolytic treatment with beta-glucuronidase/sulfatase to liberate any conjugates.
...
PMID:Determination of fumonisins in milk. 808 34

A new method was developed for the simultaneous detection and quantitation of 6-acetyl-morphine (MAM), amphetamine, benzoylecgonine (BZE), cocaine, codeine, dihydrocodeine, EDDP (methadone metabolite), methadone and morphine in hair. The hair samples were washed, cut into 2-cm segments, pulverized, incubated with phosphate buffer and beta-glucuronidase/aryl-sulfatase. After solid phase extraction and derivatization with pentafluoropropionic anhydride/pentafluoropropanol, the drugs were identified and measured by gas chromatography/mass spectrometry using their deuterated analogues as internal standards. The method is reproducible with detection limits under 0.1 ng/mg hair for almost all substances tested. Fifteen hair samples from five subjects of a methadone treatment program were collected in a 6-month period. The hair samples were segmented and examined for methadone, its main metabolite EDDP, and drugs of abuse. Of the 96 segments analysed, 95% were positive for methadone (mean value, 10.9 ng/mg), 76% for the metabolite EDDP (mean value, 1.2 ng/mg), 69% for opiates (mean values, MAM, 7.3 ng/mg; morphine, 2.9 ng/mg; codeine, 1.0 ng/mg) and 43% for cocaine (mean values, cocaine, 2.6 ng/mg; BZE, 1.1 ng/mg). A correlation of 0.63 was found between administered methadone dosages and concentrations measured by hair analysis. Further investigation is needed to clarify interindividual differences.
...
PMID:Simultaneous determination of drugs of abuse (opiates, cocaine and amphetamine) in human hair by GC/MS and its application to a methadone treatment program. 813 20

Di(2-ethylhexyl) terephthalate (DEHT) is a commercially produced chemical (Kodaflex DOTP) that is used as a general purpose, low-volatility plasticizer for polyvinyl chloride and other polymeric materials. Less than 30 million kilograms of DEHT are produced annually. DEHT is isomeric with di(2-ethylhexyl) phthalate (DEHP), a nongenotoxic rodent carcinogen whose mode of action has been suggested to derive from its ability to produce hepatocellular proliferation and/or hepatic peroxisome proliferation. Thus it is important to know the behavior of DEHT in genotoxicity assays in order to compare it with that of DEHP and other phthalate ester plasticizers. It is known from previously published studies that rats fed DEHT in the diet at 2,000 mg/kg produce urine that is negative in the Ames Salmonella bacterial mutagenicity assay in the presence and absence of induced rat liver S-9 and in the presence and absence of beta-glucuronidase/aryl sulfatase. Reported here are the results of direct testing of DEHT in the Ames plate incorporation assay, the Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) in vitro mammalian cell mutagenicity assay, and an in vitro chromosome aberrations assay using CHO cells. The results for mono(ethylhexyl) terephthalate (MEHT), a metabolite of DEHT, in the Ames Salmonella bacterial mutagenicity assay are also presented. All test results for both DEHT and MEHT were found to be negative, and it is therefore concluded that DEHT, like its isomeric relative DEHP, is not genotoxic.
...
PMID:Genetic toxicology testing of di(2-ethylhexyl) terephthalate. 816 97

Since drug-metabolizing enzymes may influence the toxic response of tissues or organs to drugs, we studied their expression in human and colon tumor tissues, in an attempt to find new targets for chemotherapy and also to explain the intrinsic drug-insensitivity of most colon tumors to anticancer drugs. In the present work, we compared human colorectal tumors and peritumoral tissues to a mouse colorectal tumor (Co38) and normal murine colon with regard to their main drug-metabolizing enzyme systems. We investigated cytochromes P-450 (1A1/1A2, 2B1/B2, 2C, 2E1, 3A) and epoxide hydrolase (EH) by immunoblotting. Total glutathione (GSH) and the activities of the following enzymes: total GST, selenium-independent glutathione peroxidase (GPX), 1,2-dichloro-4-nitrobenzene-GST (DCNB-GST), ethacrynic acid-GST (EA-GST), UDP-glucuronosyltransferase 1 (UDPGT), beta-glucuronidase (beta G), sulfotransferase (ST) and sulfatase (S) were investigated by fluorometric and spectrophotometric assays. Results obtained by immunoblotting showed that mouse colon tumor Co38 did not express any of the probed cytochromes P-450, whereas human tumors showed the presence of cytochrome P-450 3A. EH was not expressed in either mouse colon tumor Co38 or normal mouse colon, whereas it was expressed in human peritumoral and tumoral colon tissues at similar levels. GPX and EA-GST were detected in all tumoral and non tumoral tissues of both species. DCNB-GST was expressed in all murine tissues investigated, but was not found in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzymes levels, whereas mouse colon tumor Co38 had a lower expression of DCNB-GST and EA-GST compared to normal mouse colon. No significant difference was observed between human tumors and peritumoral tissues for total GST, UDPGT1, beta G, ST and S activities. For murine colon tissues, the conjugation pathways (total GST, UDPGT1 and ST) were lower in Co38, whereas the opposite was observed for the hydrolytic enzymes (beta G and S). In conclusion, despite similarities between human and murine colon tumors, mouse colon tumor Co38 appears different from human colon tumors for many drug-metabolizing enzyme systems. These interspecies differences may have implications with regard to drug screening methodologies and preclinical evaluation of candidate anticancer drugs useful in the chemotherapy of human colorectal tumors.
...
PMID:[Screening of principal enzymes involved in the metabolism of anticancer drugs in human and murine colonic tumors]. 817 93

A benztropine RIA based on polyclonal antisera raised in New Zealand white rabbits has been developed. The drug-protein conjugates employed had a variety of moles of benztropine hemisuccinate coupled per mole of protein (bovine serum albumin or bovine thyroglobulin). Six antisera were developed and the one with the highest titer was further evaluated for its cross reactivity to N-desmethylbenztropine (4%) and the antipsychotic agents fluphenazine, flupenthixol, chlorpromazine, and haloperidol (all < 1%). The selected antiserum demonstrated sufficient sensitivity to measure benztropine from 0.156 to 100 ng/mL plasma in a 200-microL plasma sample, with a mean CV of < 6%. The RIA was applied to the analysis of steady-state plasma samples obtained from patients undergoing treatment with benztropine and plasma samples obtained from human volunteers and dogs orally dosed with the drug. Both the human and dog plasma samples, when analyzed after hydrolysis with beta-glucuronidase/sulfatase, demonstrated increments in benztropine concentrations, suggesting the drug may be undergoing biotransformation to phase II metabolite(s). In addition, when benztropine was selectively extracted from the unhydrolyzed plasma samples, there was a significant decrease in drug level, which further suggested that the antiserum cross reacted with phase II metabolite(s). The shape of the plasma concentration versus time profile obtained from the dog studies suggested that the drug might also undergo enterohepatic recycling.
...
PMID:Development of a sensitive and specific radioimmunoassay for benztropine. 825 87


<< Previous 1 2 3 4 5 6 7 8 9 10

---