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)

Cultured normal human articular cartilage chondrocytes exhibited decreasing levels of arylsulfatase A and B activities when grown in the presence of increasing levels of ascorbic acid (0 to 90 mug/ml) in the media. That this was not a general effect on all lysosomal enzymes was supported by the increase in acid phosphatase activity and no change in beta-glucuronidase activity observed with increasing levels of vitamin C under identical culture conditions. No decrease in either arylsulfatase activity was observed when ascorbic acid was replaced by ascorbate-2-sulfate. Ascorbic acid did not inhibit either arylsulfatase activity when added directly to the assay mixture. These data, combined with results of mixing experiments, suggest that the effect of vitamin C is mediated through cellular factors produced in response to its inclusion in the growth media.
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PMID:Effect of ascorbic acid on arylsulfatase A and B activities in human chondrocyte cultures. 1 Oct 78

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

The effects of several antioxidants on the three major functions of human neutrophils--oxidative burst, secretion and leukotriene formation--were investigated with special emphasis on the lipophilicity. The most striking differences were obtained when ascorbate and the lipophilic ester ascorbyl palmitate were compared. As expected, the luminol- and lucigenin-dependent chemiluminescence was inhibited by all antioxidants to a different degree. Ascorbyl palmitate was able to block the biphasic luminol-dependent response completely with IC50 values of 10 and 25 microM for the first and second phase, respectively. In contrast, ascorbate only blocked efficiently the first phase of the response. The secretion of elastase was inhibited by ascorbyl palmitate dose-dependently with an IC50 value of around 200 microM, whereas ascorbate was completely inactive. Electron microscopy supported the assumption that inhibition was due to a block in degranulation and not to enzyme inactivation. This was further supported by a parallel, although somewhat lower, inhibition of other secretory enzymes like myeloperoxidase, beta-glucuronidase or lysozyme. Cells treated with the Ca2+-ionophore A23187 responded by LTB4-synthesis which was also inhibited by ascorbyl palmitate. A very efficient inhibition was observed in cell homogenates with an IC50 value of 1.5 microM. No inhibition by ascorbate was detected in both systems. Concomitant with the inhibition of 5-lipoxygenase the activity of 15-lipoxygenase increased. We conclude that cellular reductants may control neutrophil functions and that the inhibition by ascorbyl palmitate of the three processes relevant for inflammatory responses could be of therapeutic importance.
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PMID:The suppression of granulocyte functions by lipophilic antioxidants. 283 72

Pigment gallstones contain considerable amounts of unconjugated bilirubin (UCB) in the form of calcium bilirubinate and/or bilirubin polymers. Since more than 98% of bile pigments are excreted as conjugates of bilirubin, the source of this UCB needs to be identified. By using a rapid h.p.l.c. method, we compared the non-enzymic hydrolysis of bilirubin monoglucuronide (BMG) and bilirubin diglucuronide (BDG) to UCB in model bile and in native guinea-pig bile. Model biles containing 50 microM solutions of pure BMG and BDG were individually incubated in 25 mM-sodium taurocholate (NaTC) and 0.4 M-imidazole/5 mM-ascorbate buffer (TC-BUF) at 37 degrees C. Over an 8 h period, BMG hydrolysis produced 4-6 times more UCB than BDG hydrolysis. At pH 7.4, 25% of the BMG was converted into UCB, whereas only 4.5% of BDG was converted into UCB. Hydrolysis rates for both BMG and BDG followed the pH order 7.8 greater than 7.6 approximately equal to 7.4 greater than 7.1 Incubation with Ca2+ (6.2 mM) at pH 7.4 in TC-BUF resulted in precipitated bile pigment which, at 100 X magnification, appeared similar to precipitates seen in the bile of patients with pigment gallstones. At pH 7.4, lecithin (crude phosphatidylcholine) (4.2 mM) was a potent inhibitor of hydrolysis of BMG and BDG. The addition of a concentration of cholesterol equimolar with that of lecithin eliminated this inhibitory effect. Guinea-pig gallbladder bile incubated with glucaro-1,4-lactone (an inhibitor of beta-glucuronidase) underwent hydrolysis similar to the model bile systems. The non-enzymic hydrolysis of bile pigments, especially BMG, may be an important mechanism of bile-pigment precipitation and, ultimately, of gallstone formation.
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PMID:Non-enzymic hydrolysis of bilirubin mono- and diglucuronide to unconjugated bilirubin in model and native bile systems. Potential role in the formation of gallstones. 359 51

1. A partially purified lysosomal preparation was obtained from mouse liver sucrose homogenates by differential and discontinuous gradient centrifugation. 2. Triton X-100 or repeated freezing and thawing of the lysosomal suspension (subfraction B) allowed comparison of free and activated values for acid phosphohydrolase, beta-glucuronidase and N-acetylglucosaminidase in the presence and absence of ascorbate. 3. The distribution of hydrolase activities between supernatant and pellet after high-speed centrifugation was measured and the percentages of total enzyme found in the supernatant were: acid phosphohydrolase, 40.7; beta-glucuronidase, 51; N-acetylglucosaminidase, 39.4. 4. Differential rates of elution of the three hydrolases from the membrane fraction occurred with increasing Na(+) and K(+) concentrations, whereas complex biphasic elution curves were obtained as a function of bivalent cation concentration with Ca(2+) and Mg(2+). 5. Sucrose-density-gradient centrifugation of frozen-and-thawed subfraction B demonstrated highly significant changes in the protein gradient profile in the presence of a low concentration of bivalent cation, indicating membrane aggregation and enzyme-membrane association. 6. The data provide further evidence for the nature of lysosomal enzyme binding and indicate the presence of different enzyme-membrane bonds conferring structure-linked latency upon individual lysosomal enzymes.
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PMID:Effect of cations on structure-linked sedimentability of lysosomal hydrolases. 566 44

2-Hydroxyethynyloestradiol (2-OHEE2), a major biliary metabolite of 17 alpha-ethynyloestradiol in female rats, is conjugated largely with glucuronic acid. Accurate quantitation of [3H]2-OHEE2 deconjugated by enzymic hydrolysis depends upon co-incubation with ascorbate (5-10 mM). In the absence of ascorbate, the proportion of [3H]2-OHEE2 declines by 30 +/- 7% (x +/- SD, n = 4) during a 3 h incubation of bile with arylsulphohydrolase and beta-glucuronidase. Over 16 h, decomposition of the catechol leads to a decrease in ether-extractable 3H labelled components.
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PMID:Protection of catechol oestrogen from oxidation during enzymic hydrolysis of biliary conjugates. 631 Feb 65

Severance of the anterior cruciate ligament in the knees of mature beagles caused instability and resulted in the slow onset of changes comparable to those present in human osteoarthritis (OA). Heightened cellular activities were reflected in increased levels of arylsulfatase, acid phosphatase, and beta-glucuronidase in the articular cartilage. Similar increases in these lysosomal enzyme activities were found in the synovial fluid of the operated joints. Dietary supplementation with vitamin C resulted in increased serum protein content and increased cartilage formation, although ascorbate had no effect on enzyme activities. The early stages of OA in mature beagles, therefore, were characterized by interference with normal chondrocyte metabolism which resulted in staggered elevation of different lysosomal enzymes.
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PMID:Metabolic response during early stages of surgically-induced osteoarthritis in mature beagles. 720 21

The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isolated from the aerial flowering parts of Helichrysum picardii Boiss. & Reuter (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in stimulated rat peritoneal leukocytes, and for its effects on leukocyte granular enzyme release, cell viability and interactions with reactive oxygen species. Gnaphalin dose-dependently inhibited generation of the cyclo-oxygenase metabolite thromboxane B2 (IC50 = 39.9 +/- 3.9 microM), and of the 5-lipoxygenase metabolite leukotriene B4, although the potency was two-fold less (IC50 = 81.8 +/- 12.9 microM). At concentrations of 6 to 320 microM, gnaphalin did not affect secretion of the pro-inflammatory enzymes lysozyme, myeloperoxidase and beta-glucuronidase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged superoxide radicals generated in the hypoxanthine/xanthine oxidase system (IC50 = 40 microM) and by PMA-stimulated leukocytes (> 60% at 500 microM), directly inhibited xanthine oxidase (85% at 395 microM) and inhibited Fe(3+)-ascorbate-induced liposomal peroxidation (IC50 = 215 microM). Thus, like some other flavonoids found in medicinal herbs, gnaphalin possesses an array of potentially beneficial anti-eicosanoid and free-radical scavenging properties which may alongside other constituents contribute to the claimed medicinal properties of the plant from which it is derived.
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PMID:Inhibition of leukocyte eicosanoid generation and radical scavenging activity by gnaphalin, a lipophilic flavonol isolated from Helichrysum picardii. 1048 68

The physiological function of microsomal beta-glucuronidase is unclear. Substrates may be either glucuronides produced in the lumen of endoplasmic reticulum (ER) or those taken up by hepatocytes. In the latter case, efficient inward transport of glucuronides at the plasma membrane and the ER membrane would be required. Therefore, the potential role of beta-glucuronidase in ER was investigated. Isolated mouse hepatocytes and mouse and rat liver microsomal vesicles were used in the experiments. Selective permeabilization of the plasma membrane of isolated hepatocytes with saponin or digitonin resulted in an almost 4-fold elevation in the rate of beta-nitrophenol glucuronide hydrolysis, while the permeabilization of plasma membrane plus ER membrane by Triton X-100 caused a further 2-fold elevation. In microsomal vesicles, the p-nitrophenol glucuronide or phenolphthalein glucuronide beta-glucuronidase activity showed about 50% latency as revealed by alamethicin or Triton X-100 treatment. A light-scattering study indicated that the microsomes are relatively impermeable to both glucuronides and to glucuronate. On the basis of our results, the role of liver microsomal beta-glucuronidase in the deconjugation of glucuronides taken up by the liver seems unlikely. Hydrolysis of the glucuronides produced in the ER lumen may play a role in substrate supply for ascorbate synthesis or in "proofreading" of glucuronidation.
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PMID:Beta-glucuronidase latency in isolated murine hepatocytes. 1071 38

The influence of oxidized frying oil (OFO) on the guinea pig hepatic microsomal xenobiotic-metabolizing enzyme system in the presence of different amounts dietary vitamin C was investigated. Weanling male guinea pigs were divided into four groups and were fed 15% oxidized frying oil diets supplemented with vitamin C at 300, 600, or 1,500 mg/kg (experimental diets) or a control diet that contained 15% fresh untreated soybean oil with 300 mg/kg of vitamin C, respectively. After 60 d, guinea pigs were euthanized and phase I and phase II xenobiotic-metabolizing enzymes in the liver were determined. Compared with the fresh oil diet fed the control group, the relative liver weight was higher in the OFO-fed groups. Hepatic microsomal protein and cytochrome P450 contents were significantly higher in OFO-fed guinea pigs than in the control group. Both values increased in response to increased intake of vitamin C. The activities of phase II relative components, including UDP-glucuronyl transferase, UDP-glucuronyl dehydrogenase and beta-glucuronidase, of guinea pigs fed the OFO diets supplemented with 300 mg vitamin C/kg were significantly higher than those of guinea pigs fed the control diet. However, the phase II relative components decreased with increasing vitamin C content in the diet. The results demonstrate that both dietary OFO and vitamin C in guinea pigs induce hepatic xenobiotic-metabolizing enzymes, but the level of induction is modulated by the dietary vitamin C level.
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PMID:Effect of oxidized frying oil and vitamin C levels on the hepatic xenobiotic-metabolizing enzyme system of guinea pigs. 1095 80


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