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)

The authors reported previously that beta-glucuronidase in bile, especially during biliary infection with Escherichia coli, plays a substantial role in producing cium bilirubinate gallstones. In the present study, bile levels of glucaro-1:4-lactone (measured as glucaric acid) the leading inhibitor of beta-glucuronidase, were measured in both man and in rats fed high, medium, and low protein-fat diets. Glucaric acid and total bilirubin in bile correlated well in human controls but not in gallstone patients. In animal experiments, the levels of these substances in bile were high in rats on high protein-high fat and low in those on low protein-low diets. These data suggest that when bile is infected with E. coli, calcium bilirubinate gallstones seemed to form more easily in patients on low protein-low fat diet than in those consuming food rich in protein and fat. On the other hand, the ratio of lecithin to cholesterol was higher in low protein-low fat rats than in high protein-high fat rats, suggesting that cholesterol gallstones were more likely to form on the latter diet. The animal, clinical, epidemiological, and dietary data are consistent with the known trend to a decreased incidence of calcium bilirubinate and an increased incidence of cholesterol gallstones in Japan.
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PMID:Effects of diet on glucaric acid concentration in bile and the formation of calcium bilirubinate gallstones. 32 83

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

1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered to rats to study its effects on the enzyme activities of the D-glucuronic acid pathway in the liver, small intestine and kidney. 2. The UDP-glucuronosyl transferase activity of male albino rats given TCDD (80 mug/kg, one dose, i.p.) 6 days before killing was significantly increased in all tissues examined, and UDP-glucuronic acid pyrophosphatase activity was markedly decreased in the liver. D-Glucuronolactone and L-gulonate dehydrogenase activities in the liver and small intestine were slightly decreased after TCDD treatment. 3. The activities of UDP-glucose dehydrogenase and beta-glucuronidase were unchanged. 4. The 24 h urinary excretion of L-ascorbic acid was enhanced 8-fold, although no difference was detected in the excretion of D-glucaric acid between the control and experimental animals. 5. These results suggest an increased capacity for glucuronide conjugation after treatment with TCDD. 6. The lack of increase in the urinary excretion of D-glucaric acid further challenges its use as a reliable indicator of enhanced drug metabolism.
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PMID:Responses of the D-glucuronic acid pathway in rat tissues to treatment with tetrachlorodibenzodioxin. 68 88

A series of pilot studies are presented utilizing mouse and human infections with M. leprae and mouse infections with M. lepraemurium relating to the previously reported finding that hyaluronic acid seems to be a major nutrient substrate for these bacilli. The "feeding" of hyaluronic acid to the bacilli enhanced the growth of M. leprae in mouse abdominal walls and increased the Morphologic Index of M. lepraemurium infection. Saccharic acid, an inhibitor of beta-glucuronidase previously reported as present in these leprosy bacilli, caused marked regression of advanced M. lepraemurium infection, inhii. Ascorbic acid (vitamin C), also an inhibitor of beta-glucuronidase, given at a level of 1.5 gm/day for 4.5 months to one lepromatous patient without other treatment and for up to 24 months to four other lepromatous patients receiving DDS, was accompanied by lesion regression and changes in bacillary morphology similar to those seen in the inhibitor treated mice. If these observations are confirmed the possible use of beta-glucuronidase inhibitors as a useful adjunct to other leprosy therapy is raised as is also the likelihood of developing new therapies.
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PMID:Acid mucopolysaccharide metabolism in leprosy. 3. Hyaluronic acid mycobacterial growth enhancement, and growth suppression by saccharic acid and vitamin C as inhibitors of beta-glucuronidase. 109 16

A sulfatase acting upon chondroitin sulfate polymers, free of beta-glucuronidase and beta-N-acetylhexosaminidases, was isolated from extracts of the mollusc Anomalocardia brasiliana. The enzyme totally desulfates both chondroitin 4- and 6-sulfates without concomitant depolymerization of the compounds. It has no activity upon heparan sulfate, heparin, dermatan sulfate, and chondroitin sulfate disaccharides. It shows a pH of 5.0 and a temperature of 37 degrees C for optimum activity with a Km of 4 x 10(-5) M. The sulfatase is inhibited by sulfate and phosphate ions and HgCl2. The latter inhibition is reverted by sodium tetrathionate. Contrary to the sulfatases described so far the enzyme is activated by the lactone of D-saccharic acid when in the presence of beta-glucuronidase and beta-N-acetylgalactosaminidase. Several experiments indicate that the sulfatase is the first enzyme in the sequential degradation of chondroitin sulfate in the mollusc. This differs from the pathway of degradation of this compound in vertebrates and bacteria.
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PMID:Sequential degradation of chondroitin sulfate in molluscs. Desulfation of chondroitin sulfate without prior depolymerization by a novel sulfatase from Anomalocardia brasiliana. 212 69

There is now growing evidence from animal models for the possible control of different stages of the carcinogenic process by the beta-glucuronidase inhibitor D-glucaro-1,4-lactone and its precursors such as D-glucaric acid salts, D-glucarates. D-Glucaric acid is a natural, non-toxic compound produced in small amounts by mammals, including humans. It was recently found in some vegetables and fruits. D-Glucaro-1,4-lactone and D-glucarate exhibit potent antiproliferative properties in vivo. Some human subpopulations could have reduced risk of cancer development by ingesting food rich in D-glucaric acid or self-medication with D-glucarates alone or in combination with other chemopreventive agents.
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PMID:Potential use of D-glucaric acid derivatives in cancer prevention. 220 84

Dietary glucarate has previously been shown to inhibit chemical carcinogen-induced rat mammary tumorigenesis. It is demonstrated in this paper that in the mammary gland of the female Sprague-Dawley rat, feeding glucarate at a dose of 70 mmol/kg AIN76A diet for 2 weeks beginning at 35 days of age, markedly reduces [3H]thymidine labeling. Specific histochemical staining for beta-glucuronidase is used to show that the glucarate diet fed to rats for 2-4 weeks inhibits beta-glucuronidase activity in the mammary gland and has a marked antiproliferative effect on mammary epithelium. Glucarate may inhibit rat mammary carcinogenesis, in part, by changing the proliferative status of the target organ.
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PMID:Antiproliferative effect of dietary glucarate on the Sprague-Dawley rat mammary gland. 230 96

Glucarate is normally present in tissues and body fluids and is in equilibrium with D-glucaro-1,4-lactone, a natural inhibitor of beta-glucuronidase activity. Dietary calcium glucarate, a sustained-release from of glucarate, elevates the blood level of D-glucaro-1,4-lactone which suppresses blood and tissue beta-glucuronidase activity. A single dose of CaG (4.5 mmole/kg body weight) inhibited beta-glucuronidase activity in serum and liver, lung, and intestinal microsomes by 57, 44, 37, and 39%, respectively. A chronic administration of calcium glucarate (4% in diet) also decreased beta-glucuronidase activity in intestinal and liver microsomes. Maximal inhibition of beta-glucuronidase activity in serum was observed from 12 noon to 2:00 PM. In contrast, maximum inhibition of beta-glucuronidase activity in intestinal and liver microsomes occurred during mornings, although a secondary depression in intestinal microsomes also occurred around 4 PM. A 4% calcium glucarate supplemented diet also inhibited beta-glucuronidase activity by 70% and 54%, of the bacterial flora obtained from proximal (small intestine) and distal (colon) segments of intestine, respectively. Due to the potential effect of dietary glucarate on net glucuronidation and on other metabolic pathways, glucaric acid levels in various foods were determined. The glucaric acid content varied from a low of 1.12-1.73 mg/100 g for broccoli and potatoes to a high of 4.53 mg/100 g for oranges.
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PMID:Effect of calcium glucarate on beta-glucuronidase activity and glucarate content of certain vegetables and fruits. 234 74

A method for quantitation of D-glucaric acid in bile has been developed involving extraction with tetrahexylammonium chloride, boiling for 40-60 min, and determination of the percentage inhibition of beta-glucuronidase activity at 56 degrees C and pH 4. D-glucaric acid, bilirubin, bile acid, and protein were determined in 106 human gallbladder biles obtained at autopsy, including 20 with gallstones. The mean D-glucaric acid content was 1125 +/- 159 microM (mean +/- SE). Biliary beta-glucuronidase activity was not affected by D-glucaric acid because of 1) no difference in biliary D-glucaric acid content, either absolute or corrected for per unit of bilirubin, bile acid, or protein, between those with and those without gallstones; 2) no negative correlation between D-glucaric acid content and beta-glucuronidase activity in the bile; and 3) minimal conversion of D-glucaric acid to D-glucaro-1,4-lactone at the usual pH of bile. We conclude that biliary D-glucaric acid plays no role in the prevention of gallstone formation.
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PMID:Biliary D-glucaric acid: its quantitation and preventive role in gallstone formation. 235 94

The enzymes sulfatase and beta-glucuronidase from Helix pomatia were simultaneously immobilized on aminopropyl control pore glass. Once immobilized, these enzymes retained activity under varied conditions of pH, organic solvent, and temperature. To hydrolyze the sulfate and glucuronide conjugates of xenobiotics, the immobilized enzymes were either added directly to incubation mixtures for qualitative in vitro studies or packed in a short stainless steel column and placed in an HPLC system for quantitative studies. By incorporating specific inhibitors (D-saccharic acid-1,4-lactone to inhibit beta-glucuronidase or phosphate ions to inhibit sulfatase) into the incubation mixture or into the HPLC mobile phases, selective hydrolysis of either sulfate or glucuronide conjugates was achieved. Upon removal of the inhibitors from the incubation mixtures or from the mobile phases, original enzyme activity was restored. The utility of immobilized enzymes was demonstrated for quantitative analysis of sulfate and glucuronide conjugates of fenoldopam, where the liberation of the catechol aglycone moiety was necessary for electrochemical detection.
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PMID:Immobilized sulfatase:beta-glucuronidase enzymes for the qualitative and quantitative analysis of drug conjugates. 256 76


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