Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

(+)--Cyanidanol, a water-soluble flavonoid, when added to cultured skin fibroblasts of a patient with I-cell disease raised the intracellular concentration of beta-galactosidase but did not affect the distribution of arylsulfatase. A, alpha-mannosidase or beta-glucuronidase. The elevated accumulation of 35SO4 by I-cell, Hunter and Maroteaux-Lamy fibroblasts was decreased by the addition of (+)--cyanidanol to the culture medium, but the degradation of previously labeled, intracellular glycosaminoglycans was not. It is concluded that (+)--cyanidanol does not produce a biochemical correction of the enzymic abnormalities existing in I-cell fibroblasts.
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PMID:The effect of (+) --cyanidanol on lysosomal enzymes of I-cell fibroblasts. 2 Jun 73

Flavonoids are naturally occurring plant compounds that have been demonstrated to possess a variety of anti-inflammatory effects. We studied the effects of flavonoids on three aspects of neutrophil function that are commonly considered to be associated with inflammation: the release of lysosomal enzymes, the chemiluminescence (CL) response, and the production of superoxide anion. Quercetin and eight other flavonoids at a 10(-5)M concentration inhibited the neutrophil CL response to opsonized zymosan particles by approximately 60% or more. In contrast, the release of lysosomal beta-glucuronidase from neutrophils stimulated with opsonized zymosan was only inhibited by two flavonoids, quercetin and chalcone, and only at concentrations of 1.5 X 10(-4)M to 2 X 10(-4)M. Quercetin also inhibited the generation of superoxide anion by neutrophils but to a lesser degree than its effect on CL. The present studies demonstrated that certain flavonoids are not uniformly active in inhibiting neutrophil CL, beta-glucuronidase release, or superoxide generation. The effects of flavonoids on neutrophil functions probably depend on many variables including the response measured, the activating stimulus, and specific flavonoid structural features.
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PMID:Flavonoid modulation of human neutrophil function. 632 91

Quercetin inhibited in a concentration-dependent manner the release of beta-glucuronidase from human polymorphonuclear leukocytes stimulated with zymosan-activated serum. 3H-arachidonic acid-prelabelled polymorphonuclear leukocytes released 3H-arachidonic acid upon stimulation with zymosan-activated serum and this was associated with a decrease of radioactivity in the phospholipid fraction as determined by thin layer chromatography. Quercetin inhibited the release of 3H-arachidonic acid. These observations suggest that the zymosan-activated serum stimulus activates phospholipase A2 and that phospholipase A2 is inhibited by quercetin. Thus, quercetin alters polymorphonuclear leukocyte phospholipid metabolism and responses to stimulation.
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PMID:Effect of quercetin on human polymorphonuclear leukocyte lysosomal enzyme release and phospholipid metabolism. 681 14

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

Quercetin is highly mutagenic in vitro, yet is not carcinogenic when administered chronically at large doses to rodents for 12 months. We hypothesized that catechol-O-methyltransferase-catalyzed O-methylation of quercetin and other mutagenic catechol-containing flavonoids may provide an efficient inactivation in vivo and may therefore prevent tumor induction by these flavonoids. After one intraperitoneal administration of 50 mg/kg quercetin to hamsters, a urinary ether extract contained 2% quercetin and 97% 3'-O-methylquercetin. When the urine was treated first with beta-glucuronidase and sulfatase, 13% quercetin and 87% 3'-O-methylquercetin were recovered. Quercetin was rapidly O-methylated by either porcine liver or hamster kidney catechol-O-methyltransferase, with Km values of 6.1 and 6.9 microM and Vmax values of 14,870 and 200 pmol/mg of protein/min, respectively. S-Adenosyl-L-homocysteine exhibited a potent feedback inhibition of the catechol-O-methyltransferase-catalyzed O-methylation of quercetin by a competitive mechanism with respect to S-adenosyl-L-methionine and by a competitive plus noncompetitive mechanism with respect to the substrate. A comparison of the O-methylation rates and kinetic characteristics (Km, Vmax, and Vmax/Km) demonstrated that rates of O-methylation of quercetin and fisetin were up to three orders of magnitude higher than those of catechol estrogens and catecholamines. In conclusion, the rapid metabolic inactivation of mutagenic flavonoids catalyzed by catechol-O-methyltransferase may be a major reason for the lack of their carcinogenic activities in vivo.
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PMID:Catechol-O-methyltransferase-catalyzed rapid O-methylation of mutagenic flavonoids. Metabolic inactivation as a possible reason for their lack of carcinogenicity in vivo. 827 10

Quercetin is a plant polyphenol which is present in the diet as an aglycone and as sugar conjugates. Despite potent vasodilatory and antioxidant effects in vitro, destruction by intestinal organisms has been assumed to limit its nutritional relevance in the rat. However, we have refined extraction techniques using beta-glucuronidase followed by acid hydrolysis. Following this with HPLC methodology with post-column derivatisation, we have detected significant concentrations of quercetin and its metabolite, isorhamnetin, in tissues of rats maintained on quercetin-rich diets. Percentage recoveries are greater than 95% and intra-batch variation does not exceed 7% suggesting that the method may be useful in further studies of the biological role of this flavonoid.
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PMID:High-performance liquid chromatographic determination of quercetin and isorhamnetin in rat tissues using beta-glucuronidase and acid hydrolysis. 1071 59

A large number of flavonoids, mostly O-glycosides, are found in foods of plant origin. The bound sugar moiety is known to influence their bioavailability. We examined here the effect of the nature of the sugar on the absorption of the glycosides. Four groups of rats (n = 6) received a meal containing 20 mg of quercetin equivalents supplied as aglycone, quercetin 3-glucoside, quercetin 3-rhamnoside or rutin. Plasma were hydrolysed by a beta-glucuronidase/sulfatase and analyzed by HPLC coupled to UV detection at 370 nm. Four hours after the beginning of the meal, the quercetin metabolites present in plasma were identical in all groups but their total concentrations were quite different. With pure quercetin the circulating levels were 1.7 +/- 1.8 microM, but this level was three fold higher when quercetin was supplied as quercetin 3-glucoside (33.2 +/- 3.5 microM). By contrast, the plasma concentrations of quercetin metabolites was quite low with the rutin meal (about 3 microM) and undetectable after the quercetin 3-rhamnoside meal. These data suggest that the 3-O-glucosylation improves the absorption of quercetin in the small intestine, whereas the binding of a rhamnose or of a glucose-rhamnose moiety to the aglycone markedly depressed its absorption. Additionnal experiments have shown that the higher plasma levels measured after the meal containing quercetin 3-glucoside compared to quercetin were maintained throughout a 24 hour period following the meal. In conclusion, the nature of the glycosylation markedly influences the efficiency of quercetin absorption in rats. Quercetin 3-glucose can be absorbed in the small intestine and is better absorbed than quercetin itself. By contrast, glycosides containing a rhamnose moiety could not be absorbed in the small intestine.
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PMID:Respective bioavailability of quercetin aglycone and its glycosides in a rat model. 1121 81

The nature of quercetin conjugates present in blood after consumption of quercetin glucosides is still unclear. In this study, we analyzed plasma of volunteers that had consumed 325 micromol of either quercetin-3-glucoside or quercetin-4'-glucoside as an oral solution. Quercetin metabolites were extracted with acetonitrile/phosphoric acid and these extracts were analyzed using a high performance liquid chromatography with Coularray detection that distinguishes between the glucuronidated and the glucosylated forms of quercetin. No intact quercetin glucosides and only trace amounts of aglycone were found in human plasma, irrespective of the glucoside ingested. This was confirmed by spiking the plasma with glucoside standards. The major components in plasma had the same retention time as quercetin glucuronide standards. These plasma components disappeared after treatment of the plasma with bovine liver beta-glucuronidase, under reformation of quercetin, and showed the same oxidation pattern as the glucuronides. These results suggest that after consumption of quercetin glucosides, quercetin glucuronides are major metabolites in plasma.
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PMID:Quercetin glucuronides but not glucosides are present in human plasma after consumption of quercetin-3-glucoside or quercetin-4'-glucoside. 1143 10

Quercetin glucuronides are the main circulating metabolites of quercetin in humans. We hypothesise that the potential availability of the aglycone within tissues depends on the substrate specificity of the deconjugating enzyme beta-glucuronidase towards circulating flavonoid glucuronides. Human tissues (small intestine, liver and neutrophils) exhibited beta-glucuronidase against quercetin glucuronides. The various quercetin glucuronides were deconjugated at similar rates, but liver cell-free extracts were the most efficient and the activity was completely inhibited by saccharo-1,4-lactone (a beta-glucuronidase inhibitor). Furthermore, pure recombinant human beta-glucuronidase hydrolysed various flavonoid glucuronides, with a 20-fold variation in catalytic efficiency (k(cat)/K(m)=1.3x10(3) M(-1) s(-1) for equol-7-O-glucuronide and 26x10(3) M(-1) s(-1) for kaempferol-3-O-glucuronide). Similar catalytic efficiencies were obtained for quercetin O-glucuronides substituted at different positions. These results show that flavonoid glucuronides can be deconjugated by microsomal beta-glucuronidase from various human cells.
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PMID:Flavonoid glucuronides are substrates for human liver beta-glucuronidase. 1151 63

Quercetin-3- and quercetin-7-glucuronides are major products of small intestine epithelial cell metabolism (J. Nutr. 130 (2000) 2765) but it is not known if quercetin glucuronides can be further processed in the liver or if they are excreted directly. Using the HepG2 hepatic cell model, we show that highly purified quercetin-7- and quercetin-3-glucuronides can follow two pathways of metabolism: (i) methylation of the catechol functional group of both quercetin glucuronides (44% of quercetin-7-glucuronide at a rate of 2.6 nmol/hr/10(6) cells, and 32% of quercetin-3-glucuronide at a rate of 1.9 nmol/hr/10(6) cells, over 48 hr) or (ii) hydrolysis of the glucuronide by endogenous beta-glucuronidase followed by sulfation to quercetin-3'-sulfate (7% of quercetin-7-glucuronide at a rate of 0.42 nmol/hr/10(6) cells and 10% of quercetin-3-glucuronide at a rate of 0.61 nmol/hr/10(6) cells, over 48 hr). In contrast, quercetin-4'-glucuronide was not metabolised, and interestingly this is not a major product of the small intestine absorption process. The conversion of the quercetin-7- and quercetin-3-glucuronide to the mono-sulfate conjugate shows intracellular deglucuronidation by beta-glucuronidase activity, allowing transient contact of the free aglycone with the cellular environment. Inhibition of methylation using a catechol-O-methyltransferase inhibitor shifted metabolism towards sulfation, as indicated by an increase in quercetin-3'-sulfate formation (increase in rate to 1.13 and 1.43 nmol/hr/10(6) cells for quercetin-7-glucuronide and quercetin-3-glucuronide, respectively). Efflux of quercetin metabolites from HepG2 cells (methylated glucuronide and sulfate conjugates) was not altered by verapamil, a p-glycoprotein inhibitor, but efflux was competitively inhibited by MK-571, a multidrug resistant protein inhibitor, indicating a role for multidrug resistant protein in the efflux of quercetin conjugates from HepG2 cells. These results show that HepG2 cells can absorb and turnover quercetin glucuronides and that human endogenous beta-glucuronidase activity could modulate the intracellular biological activities of dietary antioxidant flavonoids.
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PMID:Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: the role of human beta-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multi-resistant protein 2 (MRP2) in flavonoid metabolism. 1252 41


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