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)

1. The metabolism of 9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine citrate (SM-10888), a cholinesterase inhibitor was studied in rat. 2. The phase I metabolite (designated M3) was isolated from urine and identified as 1-hydroxylated SM-10888 by 1H-n.m.r. and EI-MS. 3. Two glucuronides (designated SMG and M3G) were isolated from bile and urine and their structures examined by FAB-MS/MS and beta-glucuronidase hydrolysis. 4. FAB-mass spectra of SMG and M3G showed molecular ions ([M+H]+) at m/z 405 and 421, respectively. In their daughter spectra, fragment ions of aglycones (SM-10888 and M3), generated by the loss of glucuronic acid (176 amu) were observed. The daughter spectra of these aglycones were essentially similar to those of the corresponding synthetic standards. 5. SMG was hydrolysed non-enzymically at pH 5 as is often the case with N-glucuronides of arylamines. M3G could be hydrolysed by beta-glucuronidase but proved stable at pH 5. 6. From these results, SMG and M3G were concluded to be the N-glucuronide of SM-10888 and the O-glucuronide of M3, respectively.
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PMID:Metabolism of a tetrahydroaminoacridine derivative (SM-10888) in rat: structural analysis of an N-glucuronide of SM-10888 and an O-glucuronide of hydroxylated SM-10888 by FAB-MS/MS. 813 40

Egasyn is an accessory protein of beta-glucuronidase (beta-G) in the liver microsomes. Liver microsomal beta-G is stabilized within the luminal site of the microsomal vesicles by complexation with egasyn which is one of the carboxylesterase isozymes. We investigated the effects of organophosphorus compounds (OPs) such as insecticides on the dissociation of egasyn-beta-glucuronidase (EG) complex. The EG complex was easily dissociated by administration of OPs, i.e. fenitrothion, EPN, phenthionate, and bis-beta-nitrophenyl phosphate (BNPP), and resulting beta-G dissociated was released into blood, leading to the rapid and transient increase of plasma beta-G level with a concomitant decrease of liver microsomal beta-G level. In a case of phenthionate treatment, less increase in plasma beta-G level was observed, as compared with those of other OPs. This may be explained by the fact that phenthionate was easily hydrolyzed by carboxylesterase. Similarly, carbamate insecticides such as carbaryl caused rapid increase of plasma beta-G level. In contrast, no significant increase of plasma beta-G level was observed when pyrethroid insecticides were administered to rats. This is due to the fact that pyrethroids such as phenthrin and allethrin were easily hydrolyzed by A-esterase as well as carboxylesterase. On the other hand, addition of OPs to the incubation mixture containing liver microsomes caused the release of beta-G from microsomes to the medium. From these in vivo and in vitro data, it is concluded that increase of the plasma beta-G level after OP administration is much more sensitive biomarker than cholinesterase inhibition to acute intoxication of OPs and carbamates.
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PMID:Toxicological significance in the cleavage of esterase-beta-glucuronidase complex in liver microsomes by organophosphorus compounds. 1042 85

Previous reports in animals considered beta-glucuronidase activity as a novel biomarker of anticholinesterase (organophosphates and carbamates) pesticides exposure. Acid phosphatase activity was also shown to increase after organophosphates exposure. In addition, there is evidence that the paraoxonase status influences sensitivity to specific pesticides. In this study, activities of beta-glucuronidase, acid phosphatase, cholinesterase, and paraoxonase were measured in plasma from plastic greenhouse workers exposed over the long term to different pesticides, including organophosphates and carbamates, in order to evaluate the potential chronic toxicity of pesticides at occupational level. Our results show that activities of paraoxonase and cholinesterase were decreased in applicators of pesticides compared to non-applicators. Likewise, it was found that activities of beta-glucuronidase and acid phosphatase were associated with pesticide exposure in humans, and that both biochemical parameters were related to each other. Interestingly, the paraoxonase B allele (phenotyped in plasma) was associated with a higher risk of inhibition of cholinesterase activity above a 25% level, which supports the hypothesis that paraoxonase phenotypes are associated with susceptibility of humans to anticholinesterase pesticides toxicity.
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PMID:Effect of long-term exposure to pesticides on plasma esterases from plastic greenhouse workers. 1520 26

A cross-sectional study was conducted to investigate the effects of acute and chronic pesticide exposure on the plasma beta-glucuronidase enzyme activity among five patients of acute pesticide poisoning in Tengku Ampuan Rahimah Hospital, Klang, 230 farmers in the MADA area, Kedah and 49 fishermen in Setiu, Terengganu. The duration of pesticide exposure among the patients was unknown, but the plasma samples from patients were collected on day one in the hospital. The duration of pesticide exposure among the farmers was between 1 and 45 years. The beta-glucuronidase activity was compared with plasma cholinesterase activity in the same individual. The plasma cholinesterase activity was measured using Cholinesterase (PTC) Reagent set kit (Teco Diagnostics, UK) based on colorimetric method, while the plasma beta-glucuronidase activity was measured fluorometrically based on beta-glucuronidase assay. The plasma cholinesterase activity was significantly reduced (p<0.05) among the patients (1386.786+/-791.291 U/L/min) but the inhibition in plasma cholinesterase activity among the farmers (7346.5+/-1860.786 U/L/min) was not significant (p>0.05). The plasma beta-glucuronidase activity among the farmers was significantly elevated (p<0.05) (0.737+/-0.425 microM/h) but not significant among the patients (p>0.05). The plasma cholinesterase activity was positively correlated with the plasma beta-glucuronidase activity among the farmers (r=0.205, p<0.01) but not among the patients (r=0.79, p>0.05). Thus, plasma beta-glucuronidase enzyme activity can be measured as a biomarker for the chronic exposure of pesticide. However, further studies need to be performed to confirm whether plasma beta-glucuronidase can be a sensitive biomarker for anticholinesterase pesticide poisoning.
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PMID:Is plasma beta-glucuronidase a novel human biomarker for monitoring anticholinesterase pesticides exposure? A Malaysian experience. 1714 Jun 16

Acetylcholinesterase and butyrylcholinesterase (BChE) activities in blood are widely used as the biomarkers for organophosphorus insecticide (OP) exposure. In the present study, we conducted a cross-sectional study to evaluate plasma beta-glucuronidase (BG), a sensitive biomarker candidate for OP exposure, BChE activities and urinary dialkyl phosphates (DAPs), OP metabolites. We assessed the relationship between these biomarker levels in the following groups: 32 controls (control), 21 pest control operators and their co-workers who had not sprayed OPs within 3 days prior to sample collection (PCO1), and 21 pest control operators who sprayed OPs within those 3 days (PCO2). Logarithmically transformed age-adjusted means of DAPs were 3.88, 5.62 and 6.45 nmol/g creatinine for control, PCO1 and PCO2, respectively (P<0.001 for difference, P<0.001 for trend). Logarithmically transformed age-adjusted means of BG were 1.40, 1.52 and 1.85 micromol/L/h for control, PCO1 and PCO2, respectively. BG activity, but not BChE, was increased according to their OP exposure level (P=0.038 for difference, P=0.026 for trend). It was concluded that plasma BG activity is more sensitive biomarker as well as urinary OP metabolites than BChE for low-level exposure in humans.
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PMID:Beta-glucuronidase activity is a sensitive biomarker to assess low-level organophosphorus insecticide exposure. 2002 93

Plasma levels of valproic acid (VPA) are decreased by concomitant use with carbapenem antibiotics, such as panipenem (PAPM). One of the plausible mechanisms of this interaction is the inhibition of VPA glucuronide (VPA-G) hydrolysis by carbapenems in the liver. To elucidate this interaction mechanism, we purified VPA-G hydrolase from human liver cytosol, in which the hydrolytic activity was mainly located. After chromatographic purification, the VPA-G hydrolase was identified as acylpeptide hydrolase (APEH). APEH-depleted cytosol, prepared by an immunodepletion method, completely lacked the hydrolytic activity. These results demonstrate that APEH is a single enzyme involved in PAPM-sensitive VPA-G hydrolysis in cytosol. In addition, the hydrolytic activity of recombinant human APEH was inhibited by PAPM and the inhibition profile by typical esterase inhibitors (diisopropyl fluorophosphate, 5,5'-dithiobis(2-nitrobenzoic acid), p-chloromercuribenzoic acid, and d-saccharic acid 1,4-lactone) was similar to that of human liver cytosol. Cytosolic VPA-G hydrolase activity was slightly inhibited by cholinesterase and carboxylesterase inhibitors. beta-Glucuronidase activity remained in APEH-depleted cytosol, whereas VPA-G hydrolase activity was completely abolished. Thus, either cholinesterase, carboxylesterase, or beta-glucuronidase in cytosol would not be involved in VPA-G hydrolysis. Taken together, APEH plays a major role in the PAPM-sensitive VPA-G hydrolysis in the liver. These findings suggest that APEH could be a key enzyme for the drug interaction of VPA with carbapenems via VPA-G hydrolysis.
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PMID:Identification of valproic acid glucuronide hydrolase as a key enzyme for the interaction of valproic acid with carbapenem antibiotics. 2055 Dec 38


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