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)

Hyaluronic acid was purified from the horny layer of guinea pigs and its biochemical and physical properties were studied. The horny layer, obtained by applying n-hexadecane to guinea pig skin, was digested with pronase, and glycosaminoglycans in the digest were separated from UV-absorbing material by Sephadex G-75 chromatography (sample A, 17.5 mg). On DEAE-Sephadex chromatography, the fraction obtained with 0.5 M NaCl was found to contain 94% of the total uronic acid. This fraction, consisting mainly of hyaluronic acid, was dialyzed and lyophilized (sample B, 12.5 mg). Sample B, consisting of 26.1% uronic acid and 27.0% glucosamine on a dry weight basis, could be digested completely with Streptomyces hyaluronidase. Sample B had a low reduced viscosity which showed almost no concentration dependence. The intrinsic viscosity of sample B was 0.83 dl/g and its molecular weight, calculated from its viscosity, was 34,000. Sample B was eluted from Sepharose CL-6B as a broad peak between the void volume and the total column volume. The enzyme levels of hyaluronidase, beta-glucuronidase, and beta-N-acetylglucosaminidase in the n-hexadecane treated guinea pig skin increased to 1.7 to 2.5 fold those of controls after 6 days of the experiment. These results suggested that hyaluronic acid in the horny layer of n-hexadecane treated guinea pig skin might be degraded by hyaluronic acid degrading enzymes in the hyperkeratinized tissue.
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PMID:Purification and characterization of hyaluronic acid from the horny layer of guinea pigs. 674 9

We have isolated from monkey (Macaca radiata) brain lysosomal fraction by phosphomannan-Sepharose chromatography a protein that binds four different lysosomal enzymes, beta-hexosaminidase, beta-glucuronidase, alpha-L-fucosidase and arylsulfatase. The isolated protein which appeared in an aggregated homogeneous form on gel electrophoresis under non-denaturing conditions at both pH 8.3 and pH 5.0 was found to be heterogeneous on SDS-gel electrophoresis with molecular weights less than 67,000. Binding was partly abolished by periodate treatment or by alkaline phosphatase treatment of the lysosomal enzymes. Binding was completely abolished by pronase digestion of the binding protein. Of the different sugars tested for inhibition of binding, mannose-6-phosphate was most effective followed by mannose and N-acetyl glucosamine while glucose and fucose were ineffective.
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PMID:A binding protein for lysosomal enzymes isolated from brain by phosphomannan-sepharose chromatography. 684 56

Ligatin, a receptor that recognizes phosphorylated sugars, was isolated from plasma membranes of mouse macrophages, rat ileum, and rat brain. Several acidic hydrolases including N-acetyl beta-D-glucosaminidase (beta-NAG) were solubilized with this receptor. The solubilized beta-NAG bound to ligatin in vitro as demonstrated by affinity chromatography using the immobilized receptor. beta-N-Acetyl D-glucosaminidase-ligatin complexes were dissociated by low concentrations of mannose 6-phosphate (Man6P) and/or glucose 1-phosphate (Glc 1P). The effectiveness of these two phosphomonosaccharides varied depending on the source of the enzyme: ileal beta-NAG-ligatin complexes showed a four-fold preferential dissociation with Man6P; macrophage complexes showed a 160-fold preferential dissociation with Glc 1P. Brain complexes dissociated with nearly equal preference for Man6P and Glc 1P. Heterologous complexes displayed the specificity characteristic of the source of the enzyme regardless of the source of the ligatin. Treatment of the solubilized hydrolases with endoglucosaminidase H released phosphorous-32 label from these enzymes and prevented binding of beta-NAG to ligatin. However, treatment of the solubilized hydrolases with alkaline phosphatase reduced the binding of beta-NAG to ligatin by no more than 30%. This apparent resistance of beta-NAG to dephosphorylation was consistent with the chromatographic behavior of QAE of 3H-labeled acidic oligosaccharides isolated from the solubilized hydrolases. The oligosaccharides that contain phosphorylated hexose were less acidic than phosphomonoesters and were insensitive to alkaline phosphatase until subjected to acid hydrolysis. These results suggested the presence of a phosphodiester on beta-NAG analogous to the NAC glucosamine 1 P6 mannose present on beta-glucuronidase isolated from mouse lymphoma cells (Tabas I, Kornfield, S: J Biol Chem 255: 6633, 1980).
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PMID:Ligatin binds phosphohexose residues on acidic hydrolases. 729 41

High mannose-type oligosaccharides of acid hydrolases are phosphorylated by the transfer of N-acetyl-glucosamine 1-phosphate to the 6 position of mannose. This is followed by removal of the covering N-acetyl-glucosamine residue to expose a phosphomonoester. We have examined the kinetics of this phosphorylation pathway in the murine macrophage line P388D1. Cells were labeled with [2-3H]mannose for 15-20 min and then chased with unlabeled mannose for various times up to 5 h. The lysosomal enzyme beta-glucuronidase was immunoprecipitated and its oligosaccharide units examined for extent of phosphorylation and uncovering. The first phosphorylated oligosaccharides were detected after 20 min of labeling. Most of the phosphorylation occurred during the first 40 min of the chase period, and a maximum of 30% of the oligosaccharide units were eventually phosphorylated. Oligosaccharides with one and two phosphodiesters were found. The earliest detectable phosphorylated species were devoid of the glucose residues known to be present on the lipid-linked oligosaccharide precursor. Uncovering of the phosphodiesters began shortly after the oligosaccharides were phosphorylated and occurred concomitantly with the removal of outer mannose residues. Taken together, these data demonstrate that phosphorylation of lysosomal enzyme oligosaccharides is a post-translational event. Proteolytic fragmentation of [3H]mannose-labeled beta-glucuronidase and partial digestion of [3H]leucine-labeled beta-glucuronidase with endo-beta-N-acetylglucosaminidase H suggest that there are 3 glycosylation sites per subunit. Each glycosylation site is partially phosphorylated. A portion of the high mannose oligosaccharides at one site are processed to complex-type units.
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PMID:The phosphorylation of beta-glucuronidase oligosaccharides in mouse P388D1 cells. 730 50

1. The disaccharide sequences of a heparan sulfate isolated from Anomantidae sp. was determined with the aid of heparitinase I, heparitinase II from Flavobacterium heparinum, mollusc beta-glucuronidase and alpha-N-acetylglucosaminidase besides nitrous acid degradation and chemical analyses. 2. Like the mammalian heparan sulfates the mollusc heparan sulfate is composed of different oligosaccharide blocks of N-acetylated disaccharides, N-sulfated disaccharides and N,6-sulfated disaccharides and has in its nonreducing end the monosaccharide glucosamine 2,6-disulfate. 3. The oligosaccharides produced by heparitinase I degradation contain at their reducing ends a N-acetylated, 6-sulfated disaccharide. 4. These and other results lead to the conclusion that the general structure of the heparan sulfate is maintained through evolution.
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PMID:Structure of heparan sulfate from the fresh water mollusc Anomantidae sp: sequencing of its disaccharide units. 822 65

To determine the effects of lipid accumulation on proteoglycan synthesis, we studied proteoglycan biosynthesis in rabbit aortic smooth muscle cells in culture. Cholesterol-enrichment was accomplished by incubating confluent smooth muscle cells with cationized low-density lipoprotein. Control and cholesterol-enriched cells were incubated with [35S]sulphate, [3H]glucosamine, or [3H]serine. Metabolically labelled proteoglycans in the cell layer and medium were quantified. During a 20 h incubation period, proteoglycan synthesis in cholesterol-enriched cells increased by 40-50% above that in control cells. A similar increase in precursor incorporation into proteoglycans was also noted following a short 15 min pulse. The cholesterol-enriched cells also showed a 45-50% increase over control rates in the intralysosomal accumulation of a large chondroitin sulphate proteoglycan and a small dermatan sulphate proteoglycan. The enhanced synthesis of proteoglycans in cholesterol-enriched cultures was inhibited by cycloheximide and actinomycin D, which are inhibitors of protein synthesis and transcription respectively. Proteoglycan turnover was investigated by pulse-chase analysis. Following a 2-h pulse, intracellular proteoglycans in cholesterol-enriched cells disappeared, having a half-life of 26.5 h compared with 2.8 h for those in the control cells. The amount of trypsin-releasable proteoglycan was significantly reduced in cholesterol-enriched cells. In addition, the degradation of proteoglycans was severely retarded in cholesterol-enriched cultures. The activities of three acid hydrolases, N-acetyl-beta-hexosaminidase, beta-glucuronidase and cathepsin C, were significantly reduced in cholesterol-enriched cells compared with activities in control cells. The results indicate that proteoglycan metabolism is altered in cholesterol-enriched smooth muscle cells.
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PMID:Enhanced synthesis and accumulation of proteoglycans in cholesterol-enriched arterial smooth muscle cells. 837 76

The use of specific enzymes (heparinase and heparitinases from Flavobacterium heparinum, endoglucuronidase, alphaN-acetylglucosaminidase and beta-glucuronidase from the mollusc Anomalocardia brasiliana) and chemical methods (nitrous acid degradation, hydrazine N-deacetylation and borohydride reduction), led to the proposal of the total sequence of a heparan sulfate derived from bovine pancreas and partial sequences of heparan sulfates from different origins (bovine: lung, liver, brain; hog: liver, brain; rabbit liver; dog liver). It was shown that all the heparan sulfates contain common structural features such as: a N-acetylated and a N-sulfated domain made of glucuronic acid-containing disaccharides and a more sulfated region made of iduronic acid-containing disaccharides. Separating the two domains a peculiar tetrasaccharide made of GlcNAc-(alpha1-4)-IdoUA-(alpha1-4)-GlcNS-(alpha1-4)-IdoUA was identified in all the heparan sulfates analyzed. It was also shown that the non-reducing ends of the heparan sulfates contain the monosaccharides glucosamine N-sulfate and/or glucosamine 2,6 disulfate.
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PMID:Structure of heparan sulfate: identification of variable and constant oligosaccharide domains in eight heparan sulfates of different origins. 962 Apr 37

It has previously been shown that in the mollusc Anomalocardia brasiliana the desulphation of chondroitin sulphate precedes its depolymerisation by beta-glucuronidase and beta-N-acetylgalactosaminidase (Sousa Jr. et al. J. Biol. Chem. 1990;265:20150-20155). This led us to investigate whether in molluscs, sulphatases also act on heparan sulphate before its depolymerisation by glycosidases. Radioactively labelled [35S]heparan sulphate was extensively degraded by enzyme extracts prepared from the mollusc Tagelus gibbus. Several enzymes acting in concert degrade the compound to inorganic sulphate, glucosamine N-sulphate, N-acetylglucosamine-6 sulphate and other oligosaccharide products. These results indicate the presence of iduronate sulphatase, N-sulphoglucosamine 6-sulphatase alpha-N-sulphoglucosaminidase, beta-glucuronidase and alpha-L-iduronidase. The di- and mono-saccharide composition of the oligosaccharides were analysed with the aid of heparitinase II from Flavobacterium heparinum. These analyses led to the characterisation of two sulphatases that act on the polymer chain removing sulphates from the C-2 position of iduronic acid residues and the C-6 position of the glucosamine moieties, respectively. The different enzymes were partially fractionated by ion exchange chromatography and molecular sieving. These results led to the proposition of a new pathway of degradation of heparan sulphate where sulphatases act directly on the polymer chain which is then depolymerised by several glycosidases.
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PMID:New pathway of heparan sulphate degradation. Iduronate sulphatase and N-sulphoglucosamine 6-sulphatase act on the polymer chain prior to depolymerisation by a N-sulpho-glucosaminidase and glycuronidases in the mollusc Tagelus gibbus. 973 37

A new pathway of intermediary metabolism is described involving the catabolism of hyaluronan. The cell surface hyaluronan receptor, CD44, two hyaluronidases, Hyal-1 and Hyal-2, and two lysosomal enzymes, beta-glucuronidase and beta-N-acetylglucosaminidase, are involved. This metabolic cascade begins in lipid raft invaginations at the cell membrane surface. Degradation of the high-molecular-weight extracellular hyaluronan occurs in a series of discreet steps generating hyaluronan chains of decreasing sizes. The biological functions of the oligomers at each quantum step differ widely, from the space-filling, hydrating, anti-angiogenic, immunosuppressive 10(4)-kDa extracellular polymer, to 20-kDa intermediate polymers that are highly angiogenic, immuno-stimulatory, and inflammatory. This is followed by degradation to small oligomers that can induce heat shock proteins and that are anti-apoptotic. The single sugar products, glucuronic acid and a glucosamine derivative are released from lysosomes to the cytoplasm, where they become available for other metabolic cycles. There are 15 g of hyaluronan in the 70-kg individual, of which 5 g are cycled daily through this pathway. Some of the steps in this catabolic cascade can be commandeered by cancer cells in the process of growth, invasion, and metastatic spread.
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PMID:Hyaluronan catabolism: a new metabolic pathway. 1550 55

A GlcNase (exo-beta-D-glucosaminidase) was purified from culture supernatant of Amycolatopsis orientalis subsp. orientalis grown in medium with chitosan. The enzyme hydrolysed the terminal GlcN (glucosamine) residues in oligomers of GlcN with transglycosylation observed at late reaction stages. 1H-NMR spectroscopy revealed that the enzyme is a retaining glycoside hydrolase. The GlcNase also behaved as an exochitosanase against high-molecular-mass chitosan with K(m) and kcat values of 0.16 mg/ml and 2832 min(-1). On the basis of partial amino acid sequences, PCR primers were designed and used to amplify a DNA fragment which then allowed the cloning of the GlcNase gene (csxA) associated with an open reading frame of 1032 residues. The GlcNase has been classified as a member of glycoside hydrolase family 2 (GH2). Sequence alignments identified a group of CsxA-related protein sequences forming a distinct GH2 subfamily. Most of them have been annotated in databases as putative beta-mannosidases. Among these, the SAV1223 protein from Streptomyces avermitilis has been purified following gene cloning and expression in a heterologous host and shown to be a GlcNase with no detectable beta-mannosidase activity. In CsxA and all relatives, a serine-aspartate doublet replaces an asparagine residue and a glutamate residue, which were strictly conserved in previously studied GH2 members with beta-galactosidase, beta-glucuronidase or beta-mannosidase activity and shown to be directly involved in various steps of the catalytic mechanism. Alignments of several other GH2 members allowed the identification of yet another putative subfamily, characterized by a novel, serine-glutamate doublet at these positions.
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PMID:Two exo-beta-D-glucosaminidases/exochitosanases from actinomycetes define a new subfamily within family 2 of glycoside hydrolases. 1631 14


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