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)

1. 14C-Flocoumafen, administered to Japanese quail as a single oral or i.p. dose, was rapidly and extensively eliminated in excreta; most was eliminated within 24 h. Extensive metabolism of the rodenticide was seen, with at least 8 metabolites detected; unchanged flocoumafen comprised 9% dose. The elimination kinetics and metabolic profiles were qualitatively similar after oral and i.p. dosing. 2. The major metabolites (60% dose) were labile to beta-glucuronidase, liberating aglycones with identical chromatographic mobilities to those of the unchanged flocoumafen isomers. 3. Radioactivity was retained mostly in the liver; largely as unchanged flocoumafen associated with the mitochondrial and microsomal fractions. Elimination of radioactivity from most tissues was biphasic with an initially rapid depletion (5 days) followed by a slow terminal elimination phase. The elimination half life from liver was greater than 100 days. 4. Livers of quail receiving extended dietary exposure to flocoumafen at 5, 15 and 50 ppm had concentrations of flocoumafen (1.0 nmol/g) that were independent of dose, indicating a capacity-limited binding site. These hepatic concentrations were similar to those after a single oral dose and were also similar to those in rats. The data indicate the presence in quail liver of a saturable high affinity flocoumafin binding site with similar characteristics and capacity to that in the rat. 5. The selective toxicity of flocoumafen to rats (highly toxic) and quail (moderately toxic) appears to arise from differences in metabolism rather than from anticoagulant binding in the liver. When hepatic binding sites of rats are saturated anticoagulant action becomes lethal, whereas quail are able to survive and extensively metabolize the compound.
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PMID:Studies on the fate of flocoumafen in the Japanese quail (Coturnix coturnix japonica). 275 17

The proenzyme form of beta-glucuronidase is compartmentalized in large quantities within the endoplasmic reticulum by binding to the esterase, egasyn. Also, the propeptide of the proenzyme form of beta-glucuronidase is likely located at the carboxyl terminus. We have, therefore, tested if this carboxyl-terminal peptide is important in binding to egasyn. A polyclonal antibody to a 30-mer synthetic peptide, corresponding to the carboxyl-terminal 30 amino acids of pro-beta-glucuronidase, provided evidence that egasyn binds to the carboxyl terminus of beta-glucuronidase. This antibody interacted with proenzyme beta-glucuronidase-egasyn complexes in which one, two, or three egasyn molecules were bound to the beta-glucuronidase tetramer, but not with those complexes (M4) which contained four egasyn molecules. We interpret these results as indicating that all available carboxyl termini of the beta-glucuronidase proenzyme tetramer are shielded by egasyn in the M4 complexes. The same antibody did not recognize the mature lysosomal form of beta-glucuronidase, indicating that only the proenzyme form of microsomal beta-glucuronidase contains the original carboxyl terminus. Also, the synthetic 30-mer was found to be a specific and potent inhibitor (50% inhibition at 1.3 microM) of the esterase activity of purified egasyn but exhibited little inhibitory activity toward other purified esterases including a rat trifluoroacetylated esterase or egasyn esterase from another species. Together, these data describe a potent interaction of the exposed carboxyl terminus of precursor glucuronidase with the esterase catalytic site of egasyn, which in turn results in the specific localization of glucuronidase within the lumen of the endoplasmic reticulum.
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PMID:Involvement of the carboxyl-terminal propeptide of beta-glucuronidase in its compartmentalization within the endoplasmic reticulum as determined by a synthetic peptide approach. 277 65

Functional state of enzymatic systems in rat liver endoplasmic reticulum was studied. Content of cytochromes P-450 and b5 as well as activities of UDP-glucuronyl transferase, glucose-6-phosphatase, beta-glucuronidase, acetylesterase, inosine-5-diphosphatase were evaluated after permanent administration of nitrosodimethylamine within 2, 5 and 10 months at concentrations of 0.1, 1.0 and 10.0 mg/l. Content of the cancerogene active metabolites in liver cells was shown to be responsible for impairment of the functional state of microsomal enzymatic systems and was also related to intensity and duration of the nitrosodimethylamine effect. The level of these cancerogene metabolites in liver cells depended on rates of the cancerogene oxidation in the monooxygenase system and elimination of active products. At the same time, the rate of nitrosodimethylamine metabolism correlated with the doses of the substance administered into rats.
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PMID:[Effect of low concentrations of nitrosodimethylamine on the functional state of enzymatic systems in the endoplasmatic reticulum of the rat liver]. 283 31

Studies on the induction of non-oxygenative detoxication enzymes in mice by anticarcinogenic thionosulfur compounds have been extended to include hepatic and pulmonary UDP-glucuronosyltransferases. Dietary administration of disulfiram and of bisethylxanthogen to female CD-1 mice enhanced microsomal glucuronidation of 4-methylumbelliferone, a characteristic GT1 substrate, and of 4-hydroxybiphenyl, a GT2 substrate. Latency of the activity toward 4-methylumbelliferone was not affected appreciably. Disulfiram also enhanced glucuronidation of 4-nitrophenol. Diethyldithiocarbamate was ineffective under the conditions used. These thionosulfur compounds caused no significant change in beta-glucuronidase activity measured in homogenates of 7 organs.
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PMID:Differential responses of mouse UDP-glucuronosyltransferases and beta-glucuronidase to disulfiram and related compounds. 283 96

Uridine diphosphoglucuronyltransferase (UDPGT) and beta-glucuronidase (beta G) activities were measured in liver, small intestine, lung, and kidney of male Fischer rats between the ages of 2 and 30 months in order to evaluate the balance between glucuronidation and deglucuronidation reactions as a function of age. Both enzyme activities were determined colorimetrically. UDPGT was measured using both p-nitrophenol (PNP) and phenolphthalein (PT) as substrates, while p-nitrophenyl-beta-D-glucuronide was used to measure BG activity. No age-related change was detected in small intestine or lung with either enzyme. UDPGT-PT activity was only detected in liver where its activity increased about 2-fold at 96 weeks of age and remained elevated. UDPGT-PNP activity displayed a maturational decrease up to 15 weeks in liver and then remained constant with age. BG activity was measured in both the microsomal and S9 fractions of these tissues. In liver, the microsomal BG activity remained constant with age. However, in the S9 fraction, this activity displayed an increasing trend after 24 weeks. BG activity in kidney microsomes also showed this increase in both fractions. UDPGT-PNP activity in kidney extract exhibited a gradual decreasing trend with age. If these results represent the in vivo situation, the changes in the balance between glucuronidation and deglucuronidation with age not only depend on the substrate, but also on the tissue. An emphasis is placed on separating out changes due to maturation or disease from those due to senescence.
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PMID:Age-related changes in glucuronidation and deglucuronidation in liver, small intestine, lung, and kidney of male Fischer rats. 285 79

Two well-known drugs that induce the liver microsomal enzyme system in man were administered to 3 different groups of healthy male volunteers. Antipyrine 1200 mg and rifampicin in two different doses of 600 mg or 1200 mg daily were given orally to each group over a period of seven days. The extent of liver microsomal enzyme induction was assessed by estimating antipyrine elimination, serum gamma-glutamyl-transferase (GGT) activity and the urinary excretion rate of 6-beta-hydroxycortisol. In addition, possible effects on renal enzymes were monitored by measuring gamma-glutamyltransferase (GGT) and beta-glucuronidase (GRS) urinary excretion rates before and after drug administration. The possibility of a direct toxic effect on the renal tubular epithelium following drug administration was assessed by the measurement of urinary beta-N-acetylglucosaminidase (AGS) activity, total protein and glucose. Antipyrine plasma clearance and 6-beta-OHF excretion rates increased significantly in the groups treated with antipyrine or rifampicin, while serum GGT activities were enhanced only following antipyrine. Antipyrine administration increased urinary GGT excretion both immediately and one week after cessation of drug administration, but no changes were found following the administration of rifampicin. GRS, AGS, total protein and glucose excretion in urine remained unchanged during and after the administration of each individual drug. Based on these findings, the increased urinary GGT excretion observed following antipyrine treatment may be due to an inducing effect on the renal tubular cells, as no evidence for a toxic renal damage was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of antipyrine and rifampicin on the excretion of renal enzymes in human urine. 289 83

HPLC analysis of bile obtained from rats given aflatoxin B1 (AFB) demonstrates the presence of numerous polar metabolites. The glutathione conjugate derived from AFB 8,9-epoxide and the glucuronide conjugate of aflatoxin P1 (AFP) have previously been identified as the two major polar metabolites. The most polar peak present in bile from AFB-treated rats is converted to a less polar peak upon incubation with beta-glucuronidase, which has a parent ion m/e of 314 amu. Treatment of this aglycon with diazomethane produced a product which cochromatographs with aflatoxin M1 (AFM). From these data it is concluded that the most polar peak in bile from AFB-treated rats is the glucuronide conjugate of 4,9a-dihydroxyaflatoxin B1. This dihydroxy AFB metabolite was produced in vitro in mouse microsomal incubations, and time-course studies of its production suggest that it is largely formed by 9a-hydroxylation of AFP, although some may be formed by 4-O-demethylation of AFM. Direct incubation of AFP and AFM with mouse microsomes confirmed that this metabolite can be formed from both AFP and AFM. An HPLC method is described which is capable of base line resolution of this novel dihydroxyaflatoxin metabolite and eight other hydroxylated metabolites of AFB, as well as the glutathione conjugate of AFB 8,9-epoxide.
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PMID:Identification of a novel dihydroxy metabolite of aflatoxin B1 produced in vitro and in vivo in rats and mice. 297 17

The following enzymes have been studied (subcellular fractions are shown between parentheses): NAG and beta-glucuronidase (lysosomes); SDH (mitochondrial); glucose-6-phosphatase (endoplasmic reticulum); 5'-nucleotidase and (Na+, K+)Mg2+ ATPase (plasma membranes). Alterations on their activities were observed after subcutaneous injection of sex hormones, compared with controls. NAG activity from liver was always significantly decreased in lysosomal and microsomal fractions after the hormonal treatment. In the same conditions, NAG from brain was always increased. beta-Glucuronidase behaves like NAG in brain; in liver it was not modified by testosterone and it was slightly increased in lysosomal fraction after oestradiol treatment. SDH activity was not modified in mitochondrial fractions from liver, but this activity was always significantly increased in brain. Glucose-6-phosphatase activity was always significantly decreased in microsomal fractions from liver. It was increased in brain after oestradiol and testosterone injection, but medroxyprogesterone treatment caused a decreased activity. 5'-Nucleotidase and (Na+, K+)Mg2+ ATPase from brain were significantly increased in microsomal fractions by oestradiol and testosterone. Medroxyprogesterone, however, caused an increase in ATPase, but did not affect 5'-nucleotidase. Both activities in liver were decreased by oestradiol and increased by testosterone, but medroxyprogesterone caused (Na+, K+)Mg2+ ATPase to rise and 5'-nucleotidase to fall.
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PMID:Effects of oestradiol, testosterone and medroxyprogesterone on subcellular fraction marker enzyme activities from rat liver and brain. 298 29

The accumulation of the relatively large amounts of beta-glucuronidase in microsomal fractions of normal mice depends on formation of complexes with the protein egasyn. Unexpectedly, it was found that the egasyn gene also affects the processing of beta-glucuronidase, which is segregated to lysosomes. In egasyn-positive mice lysosomal beta-glucuronidase from liver has a mean pI of 5.9 with a minor proportion at pI 5.4, whereas in egasyn-negative mice the proportion of the two lysosomal forms is reversed. Combined experiments measuring susceptibility to neuraminidase and to endoglycosidase H and specific binding to Ricinus communis lectin-agarose columns showed that the alterations in isoelectric point were associated with a decrease in complex oligosaccharides of lysosomal beta-glucuronidase in egasyn-positive mice. Since this alteration occurs not only in a congenic strain carrying the Eg0 gene but also in several other inbred strains that are homozygous for this gene, it is considered to be a genuine effect of the Eg gene rather than other genes that might regulate oligosaccharide processing. Also, the alteration is likely to be a result of direct physical interaction of the egasyn protein and lysosomal beta-glucuronidase, since a second lysosomal enzyme, beta-galactosidase, which does not form complexes with egasyn, is unaffected. The results suggest a model in which egasyn not only causes accumulation of beta-glucuronidase in the microsomal compartment but also acts upon the precursor to lysosomal beta-glucuronidase to alter its interaction with trans-Golgi-apparatus processing enzymes.
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PMID:The egasyn gene affects the processing of oligosaccharides of lysosomal beta-glucuronidase in liver. 310 73

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.
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PMID:The effects of immunomodulating peptidoglycan monomer and muramyl dipeptide on hepatic microsomal UDP-glucuronyltransferase and beta-glucuronidase. 311 33


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