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)

A primary route of inactivation of leukotrienes and their receptor antagonists (LTRA) is metabolism by omega oxidation. SK&F 102922 [5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid] is a LTRA that was designed to be resistant to omega oxidation. Therefore, these experiments were designed to characterize the metabolic fate of [14C]SK&F 102922. Following iv administration of SK&F 102922 (5 mg/kg), 80% of injected radioactivity was excreted in bile in 1 hr. At least five metabolites and parent (18% of administered dose) were present in bile. One metabolite (M1), which accounted for less than 10% of the excreted radioactivity, was monohydroxylated. Three metabolites (M2, M3A, and M3B), which together accounted for greater than 50% of excreted radioactivity, had mass spectra consistent with acyl glucuronides. All three metabolites were alkali labile, whereas only one metabolite (M2) was susceptible to beta-glucuronidase hydrolysis. These data indicate that M3a and M3b are nonglycosidic isomers of M2 that were formed by a nonenzymic reaction involving migration of the aglycone (SK&F 102922) from C-1 to C-2, C-3, or C-4 of glucuronic acid. The 1-O-acyl-beta-glucuronide of SK&F 102922 (M2) exhibits pH dependent rearrangement, with half-lives ranging from 1 to greater than 1000 hr. Therefore, acyl glucuronidation can account for much of the metabolic fate of SK&F 102922 and, potentially, other structurally related LTRAs or endogenous leukotrienes themselves.
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PMID:Metabolism of the leukotriene receptor antagonist 5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid (SK&F 102922) in the guinea pig. Rearrangement of the acyl glucuronide. 135 21

Lamotrigine (LTG) is a novel triazine anticonvulsant currently undergoing clinical trials. LTG N-glucuronide, the major human metabolite of LTG, was isolated from human urine by means of XAD-2 column chromatography and semi-preparative HPLC. The structure of the suspected lamotrigine 2-N-glucuronide was proven by mass spectroscopy and NMR spectroscopy, along with chemical and enzymatic hydrolysis studies. High resolution fast atom bombardment mass spectrometry and Electrospray tandem mass spectrometry of the glucuronide gave an M+ ion at 432.0 amu and a fragment ion at 256.0 (M - 176)+ amu. The proton NMR of the glucuronide indicated the presence of a glucuronic acid moiety. A downfield anomeric proton (5.35-5.60 ppm) implied direct attachment to the aromatic triazine ring. Carbon-13 NMR of the glucuronide revealed an upfield shift (delta = -7.0 ppm) of the C-3 carbon of the triazine ring compared to LTG, indicating attachment of the glucuronide to the N-2 position. Chemical degradation or rearrangement of the glucuronide occurs at neutral pH to produce an unknown product (RP-1), while at basic pH a different unknown product (RP-2) is formed. The glucuronide is unusually stable at acidic pH. Treatment of the glucuronide with beta-glucuronidase resulted in hydrolysis to LTG, and enzymatic hydrolysis was inhibited by saccharo-1,4-lactone.
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PMID:Isolation and characterization of a novel quaternary ammonium-linked glucuronide of lamotrigine. 167 89

1. A method in use for the extraction of urinary steroid conjugates has been applied to study the recovery of synthetic steroid monoglucuronides from aqueous solution. 2. In the presence of dissolved ammonium sulphate (50g./100ml.), ether-ethanol (3:1, v/v, 3x0.5vol.) extracted the monoglucuronides of steroids of the C(18), C(19) and C(21) series, quantitatively at values pH2-9. 3. The hydrolysis of the synthetic steroid monoglucuronides by beta-glucuronidase (Patella vulgata) has been examined with reference to the pH value of the medium, enzyme concentration and substrate concentration. 4. The rate of hydrolysis of steroid monoglucuronides was dependent upon steroid structure and upon site of conjugation. 5. The rate of hydrolysis of the monoglucuronides decreased in the order C-3 (phenolic) >C-3beta>C-17beta>C-3alpha.
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PMID:The extraction and hydrolysis of steroid monoglucuronides. 596 78

We studied the bioavailability and the plasma transport of flavonols in rats fed quercetin or rutin diets. Wistar rats were fed one of the following purified diets for 10 d: control; 16.4 or 8.2 mmol rutin/kg diet; or 16.4, 8.2 or 4.1 mmol quercetin/kg diet. Flavonol concentrations were determined in plasma, ileal and cecal contents, and feces. In rats fed diets containing 16.4 mmol quercetin or rutin/kg, the concentration of circulating flavonols was approximately 115 mumol/L. Quercetin or rutin administration resulted in similar concentrations of quercetin in cecal contents. By HPLC analysis and beta-glucuronidase/sulfatase treatment, plasma flavonols have been identified as conjugated quercetin itself, or a conjugated form (4.5-fold as abundant) of an aglycone less polar than quercetin. Rats fed quercetin or rutin diets had a green/yellow-colored plasma that exhibited a peak absorbance at 411 nm, vs. 363 or 375 nm for pure rutin or quercetin solutions, respectively. This shift of band I absorption was obtained when pure quercetin was in the presence of albumin or added to a plasma fraction. The bathochromic properties of flavonoids in the presence of albumin are highly dependent on the presence of the C-2/C-3 double bond on the C-ring and are influenced by the degree of B-ring hydroxylation. The existence of intermolecular bonds between albumin and quercetin is supported by in vitro absorbance and fluorescence studies. With human albumin, the fluorescence intensity and the shift of quercetin absorbance increased in parallel to the albumin/quercetin molar ratio. Conjugated diene formation, resulting from Cu(2+)-catalyzed oxidation of human LDL or rat VLDL+LDL was effectively inhibited in vitro by 0.5 mumol/L quercetin. These results show that dietary flavonols are recovered in rat plasma as conjugated metabolites in non-negligible concentrations, and that these flavonols may be interesting antioxidant micronutrients with a variety of biological effects.
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PMID:Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. 761 8

Enzymatic hydrolyses were described for three variants of glycosidic conjugated bile acids with one beta-glucuronidase (Helix pomatia), three beta-glucosidase (almonds, sweet almonds, and Escherichia coli), and four beta-N-acetylglucosaminidase (jack beans, bovine kidney, human placenta, and Diplococcus pneumoniae) preparations. The substrates include the beta-glucuronide, beta-glucoside, and beta-N-acetylglucosaminide conjugates of bile acids related to hyodeoxycholic, murideoxycholic, chenodeoxycholic, and ursodeoxycholic acids possessing a sugar moiety at position C-3, C-6 or C-7. The comparative abilities and optimal conditions for the beta-glycosidases to catalyze the hydrolyses of the substrates were clarified by changing pHs and incubation times. Hydrolysis rates of the bile acid glycosides with beta-glycosidase treatments were influenced by both the source of the enzyme preparations and the conjugated position of a sugar moiety in the substrates, and the 3-glucoside and 3-N-acetylglucosaminide conjugates were usually hydrolyzed more efficiently than their corresponding 6- and 7-analogs. Escherichia coli and jack bean enzymes were chosen to hydrolyse the glucosidic and N-acetylglucosaminidic conjugated bile acids, respectively.
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PMID:Comparative abilities and optimal conditions for beta-glycosidase enzymes to hydrolyse the glucuronide, glucoside, and N-acetylglucosaminide conjugates of bile acids. 930 Jan 25

The cytotoxic compound, virgaureasaponin 1, was converted using several optimized enzymecatalysed hydrolyses to the 28-O-beta-D-xylopyranosyl (1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-fucopyranoside (2), and the 28-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha- L- rhamnopyranosyl-(1-->2)-beta-D-fucopyranoside (3) and 28-O-beta-D-xylyopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2) - beta-D-fucopyranoside (4) both lacking the glucose moiety at C-3 of the aglycone. The terminal rhamnose of the acylglycosidic bonded tetrasaccharide was cleaved by naringinase to give compound 2. The new acylglycosides 3 and 4 were obtained with the help of a relatively crude beta-glucuronidase preparation, but the cleavage of the sapogenin bonded glucose was impossible using several beta-glucosidase preparations directly. These derivatives were used for the investigation of the relationship between the saponin carbohydrate structure and their cytotoxic activity.
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PMID:Enzymatic hydrolysis of the cytotoxic triterpenoid glycoside virgaureasaponin 1. 974 66

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of MeA alpha C in rats was investigated. Rats were dosed with tritium-labeled MeA alpha C, and urine and feces were collected over 3 days. The metabolites of MeA alpha C were identified by high performance liquid chromatography-mass spectrometry and quantified by liquid scintillation counting. Conjugated metabolites were characterized by enzymatic hydrolyzes with beta-glucuronidase or arylsulfatase. The data showed that the metabolic pattern of MeA alpha C was similar in all rats. About 65% of the dose was excreted in urine and feces, and the major amount of MeA alpha C-metabolites was excreted during the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeA alpha C and two phase I metabolites, 6-OH-MeA alpha C and 7-OH-MeA alpha C, the following conjugated metabolites were identified: MeA alpha C-N(2)-glucuronide, A alpha C-3-CH(2)O-glucuronide, 3-carboxy-A alpha C and 3-carboxy-A alpha C-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeA alpha C and 7-OH-MeA alpha C. Also, a large amount of a rather unstable compound proposed to be of MeA alpha C-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h, and MeA alpha C and 7-OH-MeA alpha C were the only compounds identified in feces. Any activated metabolites of MeA alpha C were not detected in rat urine or feces.
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PMID:Identification of metabolites in urine and feces from rats dosed with the heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C). 1515 58

PA-457 [3-O-(3',3'-dimethylsuccinyl)-betulinic acid] represents a new class of anti-HIV drug candidates termed maturation inhibitors. After oral administration to rats, PA-457 was metabolized to several glucuronide conjugates and mainly eliminated into rat bile. Liquid chromatography-electrospray ionization-mass spectrometry analysis showed that the glucuronidation products of PA-457 were acyl glucuronides including one di-glucuronide, di-PA-457G, and two mono-glucuronides, referred to as mono-PA-457G (I) and mono-PA-457G (II), respectively. In-source fragmentation of MS spectra supported the conclusion that mono-PA-457G (I) was glucuronidated at the C-28 carboxyl of PA-457, whereas mono-PA-457G (II) was conjugated at the dimethylsuccinic acid side chain of the C-3 position. Quantification demonstrated that the predominant glucuronide of PA-457 in rat bile was mono-PA-457G (I) with lower amounts of mono-PA-457G (II) and di-PA-457G. In vitro stability indicated that the mono-acyl glucuronides of PA-457 were not degraded after incubation with 0.1 M phosphate buffer (pH 4, 7.4 and 9), plasma (human, rat, and mouse), and UDP-glucuronosyltransferase reaction media (without uridine 5'-diphosphoglucuronic acid) with microsomes (human, rat, and mouse liver microsomes), respectively, whereas the minor diglucuronide was unstable in rodent liver microsomes. All glucuronides of PA-457 could be hydrolyzed both by beta-glucuronidase and alkaline (1 M NaOH). Minor putative acyl migration products were slowly formed at pH 9, suggesting that the acyl glucuronides of PA-457 have relatively high in vitro stability.
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PMID:Structural characterization of anti-HIV drug candidate PA-457 [3-O-(3',3'-dimethylsuccinyl)-betulinic acid] and its acyl glucuronides in rat bile and evaluation of in vitro stability in human and animal liver microsomes and plasma. 1675 Dec 62