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

Glucuronidation and sulfation of 1-naphthol, 7-hydroxycoumarin, 4-nitrocatechol and phenolphthalein were studied in rabbit lung and liver. Pulmonary UDP-glucuronyltransferase and sulfotransferase activities in subcellular fractions were approximately 20-50% of those determined in the liver. Ethanol did not markedly induce these enzymes in either tissue. Glucuronidation and sulfation of 1-naphthol and 7-hydroxycoumarin were also studied in the isolated perfused rabbit lung as an intact cell model. Neither glucuronidation nor sulfation of 1-naphthol was observed. The absence of conjugate formation was due neither to the presence of beta-glucuronidase and/or sulfatase, nor to alternative biotransformation pathways. About 35% of the initial 7-hydroxycoumarin was conjugated, the majority being sulfate conjugate (14.4 nmol/h) with only minor amounts (0.12%) of the glucuronide. These results indicate the importance of studying both whole organ and in vitro metabolism.
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PMID:Glucuronidation and sulfation in subcellular fractions and in the isolated perfused rabbit lung: influence of ethanol. 190 11

The distribution of glucuronidation capacity along the rat intestine was investigated using mucosal cells, isolated from the small intestine, the caecum, and the colon plus rectum. The glucuronidation capacity for 1-naphthol decreases from 787 +/- 75 (duodenum) to 128 +/- 13 (colon plus rectum) pmoles/min X mg cell protein. The ratio between 1-naphthol and morphine glucuronidation was constant throughout the intestine (7.15 +/- 0.37). The distribution of maximal activity of UDP-glucuronosyltransferase in intestinal cell homogenates follows the same pattern. The maximal activity of UDPglucose dehydrogenase in homogenates corresponds closely to the glucuronidation rate in mucosal cells. The activity of beta-glucuronidase in intestinal cell homogenates is constant along the duodenum and jejunum but increases throughout the terminal ileum, caecum, colon and rectum. Subcellular fractionation studies using marker enzymes indicate that UDPglucose dehydrogenase and beta-glucuronidase are cytosolic enzymes in intestinal mucosal cells. Although UDP-glucuronosyltransferase activity is found in both the mitochondrial and the microsomal fractions, no indications for a mitochondrial localization of this enzyme can be found. Activity in the mitochondrial fraction appears to be due to endoplasmic reticulum, associated with the mitochondrial fraction.
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PMID:Distribution of glucuronidation capacity (1-naphthol and morphine) along the rat intestine. 393 47

Metabolism of benzo[a]pyrene (BP) was studied in mouse hepatocytes isolated from uninduced animals of C57BL/6 Jacobs (B6) and C3Hf/HeHa (C3) inbred strains. Conjugates with sulphate, glucuronate and glutathione were the major products of BP biotransformation in the intact cells. Their formation was measured by determining the radioactivity incorporated from [3H]BP into the appropriate metabolite, after separation on silica gel t.l.c. plates. The conjugates were identified by their susceptibility to the action of specific degrading enzymes, arylsulphatase, beta-glucuronidase and gamma-glutamyltransferase. Effects of inhibitors of conjugation were also examined. D-Galactosamine and diethyl maleate caused approximately 50% inhibition of the formation of glucuronide and glutathione derivatives of BP, respectively. The effect of salicylamide was less specific, besides an 88% decrease in sulphation of BP metabolites, a 40% decrease in the formation of glutathione conjugates was observed in the presence of this inhibitor. In hepatocytes of B6 mouse, all the above three types of BP conjugates were formed in almost equimolar quantities. The total formation of BP conjugates was 42% higher in B6 hepatocytes than in those of C3 strain. The most significant difference (1.7-fold) was in the production of BP glucuronides, despite an absence of observable differences between these mouse strains in the activity of microsomal UDP-glucuronosyltransferase and in the rate of 1-naphthol conjugation in isolated hepatocytes. Simultaneously, 2.5-fold higher accumulation of unconjugated BP metabolites was observed in the hepatocyte suspension of B6 than C3 strain and a 1.4-fold higher activity of aryl hydrocarbon hydroxylase in hepatic microsomes of this strain. The unconjugated metabolites of BP were separated into four major fractions by h.p.l.c. The retention times of the metabolites corresponded to trans 9,10-diol; trans 7,8-diol; 9-hydroxy- and 3-hydroxy-BP. Despite quantitative differences between B6 and C3 strains of mice in BP metabolism, the same degree of covalent binding of BP metabolites to cellular DNA, was observed. The results indicate a relatively high capacity of hepatocytes from uninduced mice for conjugation of BP metabolites. Hepatocytes isolated from various strains of mice, should be useful in elucidating the role of numerous factors in metabolism and biologic activity of BP and related carcinogens.
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PMID:Formation of glucuronide, sulphate and glutathione conjugates of benzo[a]pyrene metabolites in hepatocytes isolated from inbred strains of mice. 631 54

1. Cutaneous UDP-glucuronosyltransferase activity (E.C.2.4.1.17) was demonstrated in rat- and hairless mouse-skin microsomes using 1-naphthol as substrate. 2. Addition of the detergent Brij 35 increased the activity by approximately twofold in both species. 3. Inhibitor studies demonstrated that under the assay conditions used any UDP-glucuronic acid pyrophosphatase or beta-glucuronidase present did not interfere with the conjugation reaction. 4. Substrate inhibition was observed in hairless mouse-skin preparations and biphasic response to increasing naphthol concentration was seen in rat-skin microsomes. 5. The apparent Km values were considerably lower than those reported for liver. The sp. activity (per mg microsomal protein) in unactivated rat-skin microsomes was about 50% of that reported in unactivated rat-liver microsomes. 6. Pretreatment with 3-methylcholanthrene resulted in a small increase in cutaneous UDP-glucuronosyltransferase activities in both species.
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PMID:UDP-glucuronosyltransferase activity in rat-and hairless mouse skin-microsomes. 681 5

Cunninghamella elegans oxidized naphthalene to ethyl acetate-soluble and water-soluble metabolites. Experiments with [14C]-naphthalene indicated that 21% of the substrate was converted into metabolites. The ratio of organic-soluble metabolites to water-soluble metabolites was 76:24. The major ethyl acetate-soluble naphthalene metabolites were trans-1,2-dihydroxy-1,2-dihydro-naphthalene, 4-hydroxy-1-tetralone, and 1-naphthol. Enzymatic treatment of the aqueous phase with either arylsulfatase or beta-glucuronidase released metabolites of naphthalene that were extractable with ethyl acetate. In both cases, the major metabolite was 1-naphthol. The ratio of water-soluble sulfate conjugates to water-soluble glucuronide conjugates was 1:1. Direct analysis of the aqueous phase by high-pressure liquid and thin-layer chromatographic and mass spectrometric techniques indicated that 1-naphthyl sulfate and 1-naphthyl glucuronic acid were major water-soluble metabolites formed from the fungal metabolism of naphthalene. C. elegans oxidized biphenyl primarily to 4-hydroxy biphenyl. Deconjugation experiments with biphenyl water-soluble metabolites indicated that the glucuronide and sulfate ester of 4-hydroxy biphenyl were metabolites. The data demonstrate that sulfation and glucuronidation are major pathways in the metabolism of aromatic hydrocarbons by fungi.
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PMID:Glucuronide and sulfate conjugation in the fungal metabolism of aromatic hydrocarbons. 710 74

7-Ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), a potent anticancer agent for lung and gynecological cancers, is metabolized in vivo to the active compound, 7-ethyl-10-hydroxycamptothecin (SN-38), which is subsequently conjugated to SN-38-glucuronide by UDP-glucuronosyltransferase (UDP-GT). Three purified aglycons of natural glucuronides, baicalein, luteolin and glycyrrhetic acid, inhibited UDP-GT activity towards SN-38 as a substrate. The inhibitory potencies of these aglycons toward UDP-GT were similar to that of 1-naphthol. Based on these results, together with our previous finding that the corresponding glucuronides used in the present study strongly inhibited beta-glucuronidase in gut flora, we propose that materials in Kampo (Japanese herbal) medicines containing these aglycons of natural glucuronides could be used in vivo to decrease the enterohepatic circulation of SN-38 and other drugs.
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PMID:Inhibition of UDP-glucuronosyltransferase by aglycons of natural glucuronides in kampo medicines using SN-38 as a substrate. 749 19

Two fluorimetric HPLC methods are described for the quantification of naphthols, phenanthrols and 1-hydroxypyrene (1-OHP) in urine specimens obtained from male Wistar rats exposed to naphthalene, phenanthrene and pyrene. The polycyclic aromatic hydrocarbons (PAHs) were given intraperitoneally, either alone (1.0 mmol/kg body weight) or as an equimolar mixture (0.33 mmol/kg), using the same dosages for repeated treatments on week 1 and week 2. Between these treatments, PAH-metabolizing activities encoded by aryl hydrocarbon (Ah) receptor-controlled genes were induced in the rats with beta-naphthoflavone (betaNF). Chromatographic separation of five phenanthrols (1-, 2-, 3-, 4-, and 9-isomers) was accomplished using two different RP C-18 columns. Despite selective detection (programmable wavelengths), the quantification limits in the urine ranged widely: 1-OHP (0.18 microg/l) <phenanthrols (0.34-0.45 microg/l) <2-naphthol (1.5 microg/l) <1-naphthol (4 micro g/l). The relative standard deviation of the methods was good, as also was the reproducibility. The molar fraction of the dose excreted in 24-h urine as naphthols (<or=4.0%), phenanthrols (<or=1.1%), and 1-OHP (<or=2.4%) was low. Urinary disposition increased differentially in betaNF-induced rats: naphthols, 9-phenanthrol (1- to-2-fold); 2-, 3-, and 4-phenanthrols (4- to 5-fold); 1-phenanthrol and 1-OHP (over 11-fold). The OH-metabolites were analyzed before and after enzymatic hydrolysis (beta-glucuronidase/arylsulfatase). The percentage excreted as a free phenol in urine varied for 1-OHP (2-11%), 1-naphthol (36-51%), 2-naphthol (59-65%), and the phenanthrols (29-94%). 1-Naphthyl- and 1-pyrenyl beta- d-glucuronide served as measures for the completeness of enzymatic hydrolysis. Characteristic differences observed in the urinary disposition of naphthalene, phenanthrene, and pyrene are described, as well as important factors (dose, metabolic capacity, relative urinary output) associated with biomarker validation. This intervention study clarifies intraindividual variation in PAH metabolism and provides useful information for the development of new methods applicable in the biomonitoring of PAH exposure in humans.
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PMID:Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention with beta-naphthoflavone induction in the rat. 1269 33