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)

An earlier study of the metabolism of pentachlorophenol has shown that a metabolite, tetrachloro-p-hydroquinone, possessed pronounced inhibitory action on the activity of beta-glucuronidase from bacterial origin. Several other chlorinated hydroquinones and benzoquinones have now been studied with regard to their ability to inhibit beta-glucuronidase of various origin in vitro and in vivo. All the studied chlorinated hydroquinones and benzoquinones were found to be potent inhibitors of beta-glucuronidase of bacterial origin. D-glucaric acid-1.4-lactone was included for comparison and was found to be less active than the other studied compounds. The inhibition was found to be competitive in nature. No inhibitory effect of the benzo- and hydroquinones studied in vitro or in vivo could be demonstrated on beta-glucuronidase from livers. The result calls for precaution when using bacterial beta-glucuronidase to split urinary conjugates of glucuronic acid.
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PMID:Inhibition of beta-glucuronidase by chlorinated hydroquinones and benzoquinones. 32 81

Pentachlorophenol has earlier been shown to be metabolized in mammals to tetrachloro-p-hydroquinone. The metabolite possesses pronounced inhibitory activity on bacterial beta-glucuronidase but not on beta-glucuronidase from liver. Indirect evidence for the occurrence of both pentachlorophenol and tetrachloro-p-hydroquinone as conjugates with glucuronic acid in the urine from pentachlorophenol-treated rats is now presented. Bovine liver beta-glucuronidase has been utlizied to split the conjugates present. The in vivo metabolism of pentachlorophenol has also been studied in rats treated with phenobarbital and beta-diethylaminoethylidiphenyl propylacetate (SKF 525-A). In vitro metabolism has been studied using liver microsomes from rats pretreated with pehnobarbital. Quantitative analysis of the compounds occurring in extracts of urine or extracts from the microsomal incubates was performed by means of mass fragmentography. Pretreatment with phenobarbital increased the metabolism of pentachlorophenol to tetrachloro-p-hydroquinone both in vivo and in vitro. SKF 525-A, however, inhibited the metabolism in vitro but enhanced the metabolism in vivo when given less frequently than every 6th h. Dechlorination of pentachlorophenol is mediated by microsomal enzymes that can be induced by phenobarbital. SKF 525-A does not inhibit the dechlorination in vivo but does so in vitro.
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PMID:Metabolism of pentachlorophenol in vivo and in vitro. 58 Mar 75

After ip administration of 3-tert-butyl-4-hydroxyanisole (3-BHA) to rats, two previously undocumented metabolites 2-tert-butyl-5-methylthiohydroquinone (TBHQ-5-SMe) and 2-tert-butyl-6-methylthiohydroquinone (TBHQ-6-SMe) were identified in the urine by comparison with the authentic samples by GC/MS. In addition to these metabolites, 3-tert-butyl-4,5-dihydroxyanisole was also detected in the urine hydrolyzed by beta-glucuronidase/sulfatase. Administration of tert-butylhydroquinone (TBHQ), an O-demethylated metabolite of 3-BHA, also resulted in the formation of the S-containing metabolites, TBHQ-5-SMe and TBHQ-6-SMe. After incubation of TBHQ with rat liver microsomes in the presence of glutathione (GSH), two metabolites were isolated and purified by HPLC. The metabolites were identified as 2-tert-butyl-5-(glutathion-S-yl)hydroquinone and 2-tert-butyl-6-(glutathion-S-yl)hydroquinone by 1H- and 13C-NMR spectrometry and by fast atom bombardment-mass spectrometry. The formation of TBHQ-GSH conjugates required NADPH, molecular oxygen, and GSH. Cytochrome P-450 inhibitors such as SKF 525-A and metyrapone markedly inhibited the formation of TBHQ-GSH conjugates in vitro. These results suggest that TBHQ is converted by cytochrome P-450-mediated monooxygenases to a reactive metabolite, 2-tert-butyl-p-benzoquinone (TBQ), which then conjugates with GSH to form TBHQ-GSH conjugates. GSH S-transferase activities do not seem to play a role in GSH conjugation reaction to TBQ because cytosol fraction from rat liver homogenates did not enhance the microsome-mediated production of TBHQ-GSH conjugates.
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PMID:Identification and structure characterization of S-containing metabolites of 3-tert-butyl-4-hydroxyanisole in rat urine and liver microsomes. 168 7

The role of hyaluronidase, beta-glucuronidase and beta-N-acetylglucosaminidase in the penetration by mouse spermatozoa through the layers surrounding the oocyte was investigated by in vitro techniques. Myocrisin, fenoprofen, phosphorulated hesperidin and PS53 (a hydroquinone-sulfonic acid-formaldehyde polymer) inhibited fertilization when incubated with capacitated spermatozoa before the treated spermatozoa were mixed with intact oocytes but not when the inhibitor-treated, capacitated spermatozoa were added to oocytes free of follicle cells. The antifertility activity did not appear to be due to an effect on sperm motility or on the oocytes. These 4 compounds are known hyaluronidase inhibitors and, of the acrosomal enzymes tested, only share inhibition of hyaluronidase. Kinetic studies indicated that myocrisin is a reversible inhibitor of mouse sperm hyaluronidase whereas the other three are irreversible inhibitors. Adding saccharolactone, a beta-glucuronidase inhibitor, or N-acetylglucosaminolactone and N-acetylgalactosaminolactone, beta-N-acetylglucosaminidase inhibitors, to capacitated spermatozoa under the same conditions as the hyaluronidase inhibitors did not decrease fertilization. This was the case even though the beta-glucuronidase or beta-N-acetylglucosaminidase activities of the spermatozoa were completely inhibited, at least at the time that the inhibitor-treated, capacitated spermatozoa were mixed with the oocytes. The hyaluronidase activity of mouse spermatozoa remained unaltered during the incubation period required for capacitation; however, prolonged incubation caused a significant decrease in hyaluronidase. Untreated mouse spermatozoa caused hydrolysis of hyaluronic acid more effectively than did sperm extracts obtained by detergent extraction. These results are consistent with the theory of an essential role of hyaluronidase in mouse fertilization. At least in this species, the enzyme appears to be specifically involved in sperm penetration through the follicle cell layer. The data do not support an essential role for beta-glucuronidase and beta-N-acetylglucosaminidase in the penetration by mouse spermatozoa through the oocyte's investments. In contrast to some other species, sperm capacitation in mice does not result in a loss of hyaluronidase although part of the enzyme activity is lost on prolonged incubation. Mouse spermatozoa appear to be able to digest substrate (hyaluronic acid) even though hyaluronidase is not released.
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PMID:Effect of hyaluronidase, beta-glucuronidase and beta-N-acetylglucosaminidase inhibitors on sperm penetration of the mouse oocyte. 376 57

Biliary and urinary metabolites were examined after intravenous administration of 14C-coenzyme Q10 (14C-CoQ) to guinea pigs. Cumulative recovery of administered radioactivity for up to 8 hours by bile drainage was 4.8%. The greater part of radioactivity was detected in conjugate form. After hydrolyzing with beta-glucuronidase, aglycone fragments were subjected to methylation and reductive acetylation. The main metabolite was demonstrated to be Q acid-1 1,4-hydroquinone diacetate methyl ester (M-1) on HPLC. Then, the main metabolite was assumed to be glucuronide of 2,3-dimethoxy-5-methyl-6-(3'-methyl-5'-carboxy-2'-pentenyl)-1, 4-benzohydroquinone [Q acid-I hydroquinone]. The cumulative urinary recovery of the administered radioactivity over 48 hours was 8.3%. The labeled samples were treated similarly to bile. The urinary metabolites of CoQ10 consisted of unconjugated and conjugated forms. Lyophilized urine was treated as a bile sample and analyzed. The two major metabolites were assigned to be M-1 and Q acid-II 1,4-hydroquinone diacetate methyl ester (M-2). Then, the two metabolites were assumed to be composed of Q acid-I and 2,3-dimethoxy-5-methyl-6-(3'-carboxypropyl)-1,4-benzoquinone (Q acid-II) in free and corresponding hydroquinone conjugate forms. To investigate the effect of exogenous labeled CoQ10 on unlabeled CoQ10 (endogenous) metabolites in urine, simultaneous quantitative determination was performed using deuterium labeled CoQ10 (CoQ10-d5). Urine collected over a 72-hour period after intravenous administration of CoQ10-d5 was processed similarly to that described above and two derivatized metabolites (M-1 and M-2) were quantified by gas chromatography-mass fragmentography with the multi-ion detection method. The analytical results showed that the addition of exogenous labeled CoQ10 did not influence the metabolism (or breakdown) of unlabeled (endogenous) CoQ10.
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PMID:Metabolism of coenzyme Q10: biliary and urinary excretion study in guinea pigs. 1041 22