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 effects of short-term treatment with orally-administered zinc sulphate and/or a mixture of cholesterol/choleate on serum lipoprotein and hepatic enzyme levels were studied. Administration of graded doses of zinc sulphate (20 or 40 mg/kg, as zinc ion) for 5 days, dose-dependently increased serum and hepatic zinc levels but depressed the serum high-density lipoprotein-cholesterol (HDL-C) concentration and liver cytochrome P-450 activity. However, it did not affect hepatic concentrations of malondialdehyde and free beta-glucuronidase. Cholesterol/choleate treatment for 5 days markedly damaged the liver, as reflected by elevations of hepatic concentrations of malondialdehyde (both in the mitochondrial and microsomal fractions) and of free beta-glucuronidase; total cholesterol and low-density lipoprotein-cholesterol in the blood were increased, whereas HDL-C was decreased significantly. Concomitant administration of zinc sulphate with cholesterol/choleate further lowered HDL-C levels, but reversed the high hepatic concentrations of both malondialdehyde and free beta-glucuronidase. The present study indicates that both zinc ions and cholesterol can decrease circulatory HDL-C levels and that zinc protects against cholesterol-induced hepatic damage by reducing lysosomal enzyme release and preventing lipid peroxidation in the liver.
...
PMID:Effects of zinc and cholesterol/choleate on serum lipoproteins and the liver in rats. 273 9

Significant increases in activities of epoxide hydrolase, UDP-glucuronosyltransferase, and glutathione S-transferase, and marked reductions in cytochrome P-450 mixed-function oxidase systems occur in hyperplastic nodules induced in rat liver by chemical mutagens. In contrast, activities of both oxidative (Phase I) and conjugative (Phase II) enzymes are decreased in hepatocellular carcinomas induced by peroxisome proliferators. The present work compares alterations induced by chemical mutagens or peroxisome proliferators with changes in enzyme activities that occur in primary and secondary hepatic tumors in man. The above activities, along with beta-glucuronidase and arylsulfatase, were measured in liver samples from 6 normal livers obtained at immediate autopsy, and liver specimens obtained by surgical biopsy from the following patients: 8 with hepatomas, 5 with nonmetastatic colorectal carcinomas, and 14 with metastatic colorectal carcinomas. Cytochromes P-450MP and P-450NF in addition to epoxide hydrolase were measured by immunoquantitation. Enzymes involved in conjugation reactions were either assayed fluorometrically (UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase) or spectrophotometrically (glutathione S-transferase) using umbelliferyl substrates or 1-chloro-2,4-dinitrobenzene. Secondary hepatic tumors showed no significant change in drug-metabolizing enzymes, in contrast to primary hepatomas, which displayed decreases in all of the measured drug metabolizing enzymes. Arylsulfatase was markedly depressed in primary hepatomas (14% of normal values). Thus, activities of drug-metabolizing enzymes in human primary tumors resemble those associated with altered hepatic foci induced by peroxisome proliferators such as ciprofibrate. The marked decreases in sulfatase that occurred in primary but not in secondary human tumors suggest that sulfation of endogenous compounds and xenobiotics may differ in patients with primary and secondary hepatic tumors.
...
PMID:Hepatic drug-metabolizing enzymes in primary and secondary tumors of human liver. 302 21

The effects of immunomodulating peptidoglycans, peptidoglycan monomer (PGM) and muramyl dipeptide (MDP), on hepatic microsomal UDP-glucuronyltransferase (uridine diphosphoglucuronate glucuronosyl transferase, EC 2.4.1.17) and beta-glucuronidase (beta-D-glucuronide glucuronohydrolase, EC 3.2.1.31) were tested in female C57Bl mice. 4-Methylumbelliferone and p-nitrophenol were used as representative substrates for one functional form of UDP-glucuronyltransferase (GT1) and testosterone for the second functional form (GT2) of the enzyme. Both PGM and MDP were found to transiently inhibit the activity of UDP-glucuronyltransferase. There was no significant difference in the magnitude of inhibition of the two functionally different enzyme forms. The activity of microsomal beta-glucuronidase was tested using 4-methylumbelliferyl glucuronide and p-nitrophenyl glucuronide as substrates. Time dependent transient inhibition of beta-glucuronidase activity was observed with both peptidoglycans. In addition, the effect of MDP on cytochrome P-450 was tested, since we have shown previously that PGM affected this system. MDP decreased the content of cytochrome P-450 and inhibited the activity of related enzymes.
...
PMID:The effects of immunomodulating peptidoglycan monomer and muramyl dipeptide on hepatic microsomal UDP-glucuronyltransferase and beta-glucuronidase. 311 33

Identifying individuals with a deficient capacity for oxidative drug metabolism is of increasing clinical importance. Dextromethorphan (DM) is gaining wide acceptance as a probe drug to characterize individual expression of a specific cytochrome P-450 isozyme. The thin-layer chromatography (TLC) technique described in the present study is a rapid and inexpensive alternative to the methods currently available for assessing the urinary metabolic profile of DM. Sixty-five healthy volunteers participated in the study by ingesting 213 mmol DM and collecting all urine for the ensuing 8 h. Urine samples were analyzed by TLC and high-performance liquid chromatography (HPLC) after treatment with beta-glucuronidase. Based on the relative color intensities of DM and its O-demethylated metabolite, dextrorphan, the TLC analysis provided an accurate phenotype assessment. A greater intensity of the parent drug relative to the metabolite indicates a poor metabolizer phenotype whereas a reversed relative intensity indicates the extensive metabolizer phenotype. The phenotype assignments made by TLC were verified by comparison with the quantitative results (based on metabolic ratios) obtained from HPLC analysis. Complete agreement was found between the two methods. The routine implementation of phenotype determination into clinical protocols can be realized with this facile TLC technique.
...
PMID:Simplified phenotyping with dextromethorphan by thin-layer chromatography: application to clinical laboratory screening for deficiencies in oxidative drug metabolism. 320 36

Urine and plasma concentrations of methoxyphenamine (MP) and three of its metabolites were determined after a single oral 60.3 mg dose of MP hydrochloride to healthy subjects of known debrisoquin (D) phenotype. Urine was collected from five extensive (EM) and five poor (PM) metabolizers of D for 12 hours and analyzed after treatment with beta-glucuronidase/sulfatase. There were marked interphenotype differences in the total urinary excretion of O-demethylmethoxyphenamine (ODMP) and 5-hydroxymethoxyphenamine (5HMP), as well as in MP/ODMP and MP/5HMP ratios. In contrast, the urinary output of N-demethylmethoxyphenamine (NDMP) or MP/NDMP ratios showed no interphenotype differences. Plasma data from two EMs and two PMs showed that the mean values for maximum concentration t1/2, and total AUC for MP were two-, three-, and sixfold greater, respectively, in PMs than in EMs. The plasma levels of ODMP and 5HMP were higher in EMs than in PMs, whereas the converse was true for NDMP. Thus, O-demethylation and aromatic 5-hydroxylation of MP are defective in PMs of D, resulting in increased MP and NDMP plasma levels. The form of cytochrome P-450 involved in the N-demethylation of MP is different from that responsible for O-demethylation and aromatic 5-hydroxylation.
...
PMID:Metabolism of methoxyphenamine in extensive and poor metabolizers of debrisoquin. 401 14

The activities of several enzymes involved in hepatic ascorbic acid synthesis and the requirement of dietary ascorbic acid were investigated in the OD (osteogenic disorder) rat, which has a hereditary defect in ascorbic acid-synthesizing ability. No activity of hepatic L-gulonolactone oxidase was detected in OD rats. However, OD rats maintained the normal activities of hepatic UDPglucose dehydrogenase, UDPglucuronyl transferase and beta-glucuronidase. Hemorrhage in muscle and leg joints, lower hepatic content of cytochrome P-450 and lower activities of hepatic drug-metabolizing enzymes, higher serum and adrenal levels of corticosterone and lower urinary excretion of hydroxyproline were observed in ascorbic acid-deficient OD rats than in OD rats fed 300 mg ascorbic acid/kilogram diet. Consequently, we conclude that OD rats cannot synthesize ascorbic acid because of the lack of activity of hepatic L-gulonolactone oxidase and that the dietary addition of about 300 mg ascorbic acid (per kilogram diet) is enough to prevent signs of vitamin C deficiency and to achieve maximum growth, and that more than 300 mg ascorbic acid per kilogram diet may be required for the maximum activity of hepatic drug-metabolizing enzymes.
...
PMID:Requirement for ascorbic acid in a rat mutant unable to synthesize ascorbic acid. 406 54

A method is described for preparing and maintaining an isolated perfused and ventilated mouse lung. The preparation is especially suited for studying xenobiotic metabolism or toxicological interactions, in a species with a broad spectrum of studies in pulmonary toxicology. The preparation is viable with respect to drug metabolism for up to two hours, as judged from studies of aniline oxidation to p-aminophenol. With [14C]-benzo(a)pyrene as substrate for the lungs of male ICR Swiss mice, the major ethyl acetate-extractable metabolites are the 3-hydroxy, 9,10-dihydrodiol, 7,8-dihydrodiol, and 4,5-dihydrodiol derivatives. The rates of individual BaP metabolite production are increased in lungs from mice pretreated with Aroclor 1254 or beta-naphthoflavone, substances known to induce increased synthesis of cytochrome P-450. Small amounts of water-soluble BaP metabolites were hydrolyzed by beta-glucuronidase and aryl sulfatase, suggesting the presence of enzymes required for these conjugations. These results support the existence of significant cytochrome P-450-dependent and conjugative BaP metabolism in the intact mouse lung, similar to that examined in other species, and capable of contributing to the systemic metabolism of this carcinogen.
...
PMID:Benzo(a)pyrene metabolism in the isolated perfused mouse lung. 631 13

Chronic alcohol intoxication led to an increase in activity of alcohol dehydrogenase and to decrease -- of aldehyde dehydrogenase and the microsomal ethanol oxidizing system (MEOS) with simultaneous activation of cytochrome P-450 in liver tissue of rats during ontogenesis. Ethanol, which did not affect the enzymatic status of lysosomes within ontogenesis (alpha- and beta-glucosidases, alpha- and beta-galactosidases, alpha-mannosidase, beta-N-acetylglucosaminidase, beta-xylosidase, beta-glucuronidase, beta-N-acetyl galactosaminidase acid RNAase, arylsulfatases A and B, cathepsin D), activated the majority of hydrolases in both embryonal and postnatal periods of development. Distinct increase in lipoperoxidation was detected under conditions of chronic alcohol intoxication.
...
PMID:[Enzyme characteristics of the rat liver in ontogeny in chronic alcohol intoxication]. 720 88

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

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)
...
PMID:Increased renal drug metabolism in treadmill-exercised Fischer-344 male rats. 810 May 4


<< Previous 1 2 3 4 Next >>

---