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)

The enzymatic activity of bacterial beta-glucuronidase plays an essential role in the formation of calcium bilirubinate in bile. There are, however, many unsettled problems such as methodology of the assay for its enzymatic activity. In the present study (1) the azopigments from monoconjugated bilirubin (MCB) and unconjugated bilirubin (UCB) in native bile were semiquantitatively determined, (2) the deconjugation of conjugated bilirubin (CB) in bile was estimated with azopigment analysis and (3) factors affecting the deconjugation of CB in bile, especially for pH value, were investigated. CB in bile was stable at physiologic pH during 6-hr incubation at 37 degrees C, but was hydrolyzed at alkaline pH. At physiologic pH, addition of beta-glucuronidase from E. coli hydrolyzed CB in bile and increased MCB and UCB in bile. Based upon the results mentioned above, it is suggested that alkaline pH and enzymatic activity of beta-glucuronidase should cause the increase of UCB in bile. It can be said that beta-glucuronidase is essential for the formation of calcium bilirubinate gallstone at physiologic pH.
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PMID:Effects of pH on the deconjugation of conjugated bilirubin in human bile. 391 93

Human bile contains a considerable amount of endogenous beta-glucuronidase. The effects of pH and bile acids on its activity have been studied in regard to its role in the pathogenesis of cholelithiasis. beta-Glucuronidase, purified from human liver to homogeneity, was structurally stable between pH 4 and 10, but was active only over a much narrower range of pH, with a pH optimum of 5.2. The inactivation below pH 4 was due to its irreversible denaturation, whereas the inactivation at higher pH was due to a true reversible pH effect on the enzyme velocity. Kinetic studies revealed that hydrogen ion acted as a substrate-directed activator of the free enzyme, but not the enzyme-substrate complex, with a molecular dissociation constant of 4 X 10(-6). The enzyme activity was not affected by unconjugated bile acids, primarily due to their extremely low water solubility. Conjugated bile acids, on the other hand, exerted heterogeneous and pH-dependent effects on the enzyme. At pH 5.2, taurocholic acid and glycocholic acid were substrate-directed activators of the enzyme; taurochenodeoxycholic acid and taurodeoxycholic acid, competitive inhibitors; and glycochenodeoxycholic acid and glycodeoxycholic acid, mixed inhibitors. At pH 7.0 all taurine and glycine conjugates behaved as substrate-directed activators. Though beta-glucuronidase activity at pH 7 was only 23% of its maximal activity at pH 5.2, conjugated bile acids tended to restore its activity to a certain extent at pH 7. Thus, endogenous beta-glucuronidase could play a significant role in pigment cholelithiasis.
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PMID:Human beta-glucuronidase. Studies on the effects of pH and bile acids in regard to its role in the pathogenesis of cholelithiasis. 397 Sep 37

Abnormally low activity of hepatic bilirubin UDP-glucuronosyltransferase was found in 25% of 81 unselected patients with gallstones, as compared with only 3% in 35 controls. At the time of cholecystectomy, the stones were taken for analysis in 48 of 81 patients, and a bile sample was obtained in 42 of them. Among the stones, 75% were cholesterol stones, 15% pigment stones, and 10% 'intermediate' stones. Low hepatic conjugating activity was not preferentially associated with a given type of stone. No relation was found between the enzymic deficiency and the biliary cholesterol saturation index. A high proportion of biliary bilirubin monoglucuronide (over 40%) was found in four of seven patients with low transferase activity, as was earlier demonstrated in patients with overt Gilbert's syndrome. Raised biliary bilirubin monoglucuronide was also found in three patients, out of 46, who had normal transferase but raised biliary beta-glucuronidase activity. There was no evidence that deficient bilirubin conjugation could be a consequence of gallstones: the activity of another hepatic microsomal enzyme, glucose 6-phosphatase, taken as a reference, was measured in 12 patients and was always normal. Taking into account the very high frequency of a bilirubin centre in the cholesterol stones (87% of the cases in the present series), it is suggested that the increased proportion in poorly soluble biliary bilirubin monoglucuronide, which was associated with defective conjugation, could act as a trigger for gallstone initiation, regardless of the final composition of the stone.
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PMID:Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones. 625 64

Hepatolithiasis is associated with bile stasis and bacterial infection. Gallstones found in the intrahepatic bile duct are mostly calcium bilirubinate stones, the presence of which is closely related to the presence of bacteria. In the present study, a high incidence of bile infection was found in hepatolithiasis: 52 of 54 cases (96.3%). This is in concordance with the other reports from Japan as well as from East Asia. E coli was the most frequent isolate followed by Klebsiella, Streptococcus (D), and Pseudomonas. Because of the frequent isolation of E coli in calcium bilirubinate stone cases, beta-glucuronidase from E coli has been thought to be responsible for the formation of calcium bilirubinate stones by effecting hydrolysis of bilirubin glucuronide to free bilirubin, which is insoluble in water. The recent introduction of improved anaerobic culture techniques has led to an increasing number of reports on the presence of anaerobes in the biliary tract. Anaerobes were isolated in 6 of 29 cases of hepatolithiasis (20.7%) in our series but more frequently in Kaohsiung, Taiwan (25 of 57 cases, or 44.4%). Bacteroides and Clostridium were the most frequent isolates from the biliary tract and were shown to have beta-glucuronidase activity. Anaerobes were often found together with aerobes, suggesting the possibility of a synergistic effect that may influence the occurrence and development of cholangitis, which is often associated with hepatolithiasis. Though the biliary tract and liver are usually sterile, when an infection of the biliary tract occurs the route by which bacteria reach the region is thought to be hematogenous, lymphatic, or direct intraluminal ascending infection, the last being the most likely. Treatment of cholangitis associated with hepatolithiasis should be directed toward the removal of stones and termination of bile stasis. When cholangitis ensues, control of bacterial infection by antibiotics should be started without delay. The choice of antibiotics in controlling cholangitis is presented.
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PMID:Bacteriology of hepatolithiasis. 638 75

Pigment gallstones are of two major types, black and earthy brown, each consisting of calcium salts of bilirubin and other anions, along with an unmeasured residue that is largely mucin glycoproteins. Studies in model systems indicate that the small proportion of unconjugated bilirubin in bile is solubilized by bile salts and that the ionized bilirubin is more soluble than the protonated diacid. Solubility is decreased by added lecithin but is unaffected by cholesterol. At the pH of bile, unconjugated bilirubin exists mainly as a monoanion with sufficient solubility in mixed micelles not to precipitate, were it not for the presence of calcium, which forms highly insoluble salts with unconjugated bilirubin anions. Supersaturation of bile with calcium bilirubinates is inhibited by bile salts, which bind calcium, reducing the activity of free calcium ions. When supersaturation occurs, usually due to increased concentrations of bilirubinate anion, nucleation may be initiated by binding of calcium bilirubinate to mucin glycoproteins in bile. In earthy brown stones, which form mainly in the bile ducts, the pigment is mostly calcium bilirubinate, combined with calcium palmitate. These components form due to hydrolysis, by enzymes in infecting bacteria, of conjugated bilirubin and lecithin, respectively. In black stones, which form mainly in the gallbladder, the pigment is mostly a highly cross-linked network polymer of bilirubin, which is insoluble in all solvents. Concomitant polymerization and oxidation of calcium bilirubinate probably occur in the solid state, after precipitation of the pigment due to hydrolysis of conjugated bilirubin by endogenous beta-glucuronidase from the biliary tract and/or liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The etiology of pigment gallstones. 643 94

A new possible pathogenesis of gallstones is described. The theory is based on the presence of indolic melanin precursors in biological fluids. It is proposed that the increased concentration of these compounds in bile could lead to the formation of melanin polymer as a network nucleus for a future concrement. An activation of the pigmentary system (e.g. insolation, gravidity) and the presence of hydrolytic enzymes (beta-glucuronidase and/or arylsulphatase) in biliary tract might belong to the risk factors of gallstone formation. The detection of 5-hydroxy-6-methoxyindolyl-2-carboxylic acid in bile and 5,6-dihydroxyindole in the extract of an alkali fused gallstone provided the first support of this theory.
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PMID:A new possible pathogenesis of some gallstones. 647 56

The calcium bilirubinate stone is the typical gallstone found in patients with hepatolithiasis; a series of studies on the formation of stones have been performed by Maki [1966, 1982]. Results of chemical analysis and clinical factors lend support to Maki's bacterial beta-glucuronidase theory [Maki, 1966]. However, besides calcium bilirubinate these stones also contain other components such as fatty acids and free bile acids. The presence of these components indicates bacterial involvement, which is proved by the decomposition of the lecithine in bile to fatty acids by phospholipase A and the formation of free bile acids by deconjugation of the conjugated bile acids. In the formation of calcium bilirubinate stones, it is believed that diet [Matsushiro et al, 1977] and bacterial infections accompanying biliary stasis are important inducing elements. Since these stones are formed mainly in the bile ducts and recurrence rates are likely to be high, it is important from the therapeutic viewpoint to remove these inducing factors. However, it is still uncertain whether bacterial infection accompanying biliary stasis should be considered as an inducing factor in the development of fatty acid-calcium stones. More than 90% of all cholesterol and black stones are found in the gallbladder. However, when these stones are found in the intrahepatic bile ducts, it is still not clear whether they are expelled from the gallbladder or formed initially in the intrahepatic bile ducts. In patients who have cholesterol stones filling the entire biliary tract, it is difficult to conceive that these gallstones are first expelled from the gallbladder. In addition, in patients with black stones, the stones are located only in the dilated bile ducts, and stenosis of the bile duct is often recognized in the excisional stump of the liver at lateral segmentectomy. In these cases, the expulsion of stones from the gallbladder seems rather improbable. Different types of gallstones show a tendency to occur in certain regions; however, gallstones may be formed in almost any part of the biliary system if conditions are favorable. It can be concluded that the pathogenesis of hepatolithiasis may not be clarified only by analysis of the intrahepatic gallstones. In addition, an understanding of the formation of different types of gallstones may contribute to elucidation of the pathogenesis of hepatolithiasis.
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PMID:Types and chemical composition of intrahepatic stones. 647 92

Currently, the incidence of the upper stenotic type and intrahepatic stenotic type have been increasing in number. These changes may be attributed to the improvements of the diagnostic tools for hepatobiliary diseases, especially in the progress of imaging methods. In view of the type of gallstone, most intrahepatic gallstones are the calcium bilirubinate stones generated on the basis of bile stasis and bacterial infection. For the formation of calcium bilirubinate stones the mutual relationship of bacterial beta-glucuronidase and glucaro-1, 4-lactone in the bile is thought to important. Free bile acids and fatty acids are detected in fairly large amount in calcium bilirubinate stones. This suggests that precipitation of calcium bilirubinate in the bile may coincidently occur with the deconjugation of the conjugated bile acids and decomposition of lecithin. In the formation of calcium bilirubinate stones, it is believed that diet and bacterial infection accompanying biliary stasis are important inducements. Since these stones are formed mainly in bile ducts and recurrence rates are likely to high, it is important to remove these inducements from therapeutic viewpoint.
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PMID:[Infected bile and intrahepatic gallstones]. 650 69

Bile pigment gallstones were produced in six of six mongrel dogs by narrowing the cystic duct with ligature after a postoperative interval of seven days. beta-Glucuronidase producing group G Streptococcus and Staphylococcus aureus were found in the bile, the gallbladder wall, and the liver. In another trial similar gallstones were produced in four of eight dogs after mere injection of beta-glucuronidase producing Escherichia coli into the spleen resp. in six of eight dogs after injection of E. coli into the colon without ligature of the cystic duct. In an additional series gallstones were produced in six dogs after injection of beta-glucuronidase producing E. coli into the colon plus ligature of the cystic duct. The injected strain of E. coli was found in the bile, the gallbladder wall, the liver, and even within the produced gallstones. In a control group in none of six dogs gallstones were present. beta-Glucuronidase producing group G Streptococcus was found in the gallbladder of one dog, Pseudomonas aeruginosa was found in the gallbladder of another dog and Staphylococcus aureus in the liver and gallbladder wall of a third dog. We conclude from our experiments that merely bacterial infection of the biliary tract can lead to gallstone formation. The bacterial colonization of the liver and the biliary tract is promoted by biliary tract obstruction. beta-Glucuronidase producing bacteria increase the amount of beta-glucuronidase in the bile thus leading to calcium bilirubinate precipitation and gallstone formation by deconjugation of bilirubindiglucuronide.
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PMID:[Experimental gallstone formation. Etiological significance of beta-glucuronidase producing bacteria and biliary obstruction]. 685 81

Two hundred consecutive gallstone cases have been subjected to bacteriological study employing improved anaerobic culture techniques. In addition to Clostridia species, species of anaerobes such as Bacteroides fragilis, Peptococcus, Veillonella, and Eubacterium are found to be present, some of which possessed beta-glucuronidase activity. This finding has a certain bearing on the etiology of bile pigment calcium stones. In addition to Escherichia coli, Bacteroides and Clostridium often found in the biliary tract may contribute to the formation of bile pigment calcium stones by producing beta-glucuronidase and thus deconjugating bilirubin diglucuronide to form free unconjugated bilirubin which in turn combines with calcium, leading to stone formation. In contrast, very low bacterial incidence was associated with cholesterol stones and so-called black stones--sometimes called pure pigment stones--and thus bacteria play little role, if any, in their formation. Therefore, bile pigment calcium stones and so-called black stones, which are often classified as pigment stones indiscriminately, should be differentiated not only because of their difference in their appearance and composition but also in their etiological background. Regardless of the kind of stones present in the common duct, the incidence of bacteria was found to be increased.
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PMID:Bacteria and gallstones. Etiological significance. 723 47


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