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)

Various oligosaccharides from hyaluronic acid, which have glucuronic acid or N- acetylglucosamine at the nonreducing terminal, were prepared by digestion with a combination of testicular hyaluronidase and beta-glucuronidase. These oligo saccharides were analyzed by negative-mode ion-spray mass spectrometry (MS) with an atmospheric pressure ion source. Introduction of collisionally activated dissociation tandem mass spectrometry (CAD-MS/MS) produced ions derived from cleavage of the glycosidic bonds, allowing the structure to be analyzed. The CAD-MS/MS spectrum showed an intense and characteristic fragment ion at m/z 193 for oligosaccharides having glucuronic acid at the nonreducing terminal. On the other hand, this ion was not observed in the spectra of oligosaccharides having N- acetylglucosamine at the nonreducing terminal. Therefore, the fragmentation pattern revealed by CAD-MS/MS provides useful information for distinguishing glucuronic acid and N- acetylglucosamine at the nonreducing terminal of oligosaccharides derived from hyaluronic acid and other glycosaminoglycans. This ion-spray CAD-MS/MS technique was also applied successfully to the characterization of glycosaminoglycans reconstructed by glycotechnology.
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PMID:Ion-spray mass spectrometry for identification of the nonreducing terminal sugar of glycosaminoglycan. 962 Nov 12

Involvement of enzymes catabolizing hyaluronic acid (hyaluronidase, beta-glucuronidase, N-acetyl-beta-D-hexosaminidase) in the hydroosmotic action of vasopressin on the amphibian urinary bladder Rana Ridibunda was studied. It was found that vasopressin (50 nM), agonist of V2 receptors dDAVP (1.5 mcM) and forscolin (30 mcM) induce an activation of enzymes and its release into the Ringer solution at the mucosal surface simultaneously with the increase in the osmotic water flow. Maximal effect was observed 10 min later than hydroosmotic response. Release of enzymes under vasopressin effect was found in the absence of osmotic gradient and water flow through the epithelium. The repeated substitution of the outer Ringer solution for the fresh one resulted in the increase in the both the water permeability and the release of enzymes through the mucosal surface. We suggested that involvement of hyaluronate-hydrolases in the vasopressin effect is mediated by the cAMP-dependent mechanism. It is supposed that this effect creates conditions for the increase in the permeability of glycosaminoglycan structures covering adjacent to the apical cell surface.
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PMID:[Hyaluronate-hydrolases system and hydroosmotic effect of vasopressin]. 1051 5

The involvement of enzymes catabolizing hyaluronic acid (hyaluronidase, beta-glucuronidase, N-acetyl-beta-D-hexosaminidase) in the hydroosmotic effect of vasopressin in the frog (Rana ridibunda) urinary bladder was studied. It was observed that vasopressin (50 nM), an agonist of V2 receptors, L-desamino-8-D-arginine-vasopressin (dDAVP, 1.5 microM) and forskolin (30 microM) activated the enzymes and caused their release into Ringer solution at the mucosal side, together with an increase in osmotic water flow. The effect of AVP on enzyme activity developed 10 min after the hydroosmotic response. Cytochalasin B (a specific inhibitor of actin filament elongation, 50 nM) blocked the hydroosmotic response to AVP; hyaluronate hydrolase activity increased in the bladder tissue but not in Ringer solution. It is suggested that the involvement of hyaluronate hydrolases in AVP's effect is mediated by a cAMP-dependent mechanism and provides favorable conditions for an increase in the permeability of glycosaminoglycan structures adjacent to the apical cell surface.
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PMID:Effects of vasopressin on hyaluronate hydrolase activities and water permeability in the frog urinary bladder. 1169 69

The human genome contains six hyaluronidase-like genes. Three genes (HYAL1, HYAL2 and HYAL3) are clustered on chromosome 3p21.3, and another two genes (HYAL4 and PH-20/SPAM1) and one expressed pseudogene (HYALP1) are similarly clustered on chromosome 7q31.3. The extensive homology between the different hyaluronidase genes suggests ancient gene duplication, followed by en masse block duplication, events that occurred before the emergence of modern mammals. Very recently we have found that the mouse genome also has six hyaluronidase-like genes that are also grouped into two clusters of three, in regions syntenic with the human genome. Surprisingly, the mouse ortholog of HYALP1 does not contain any mutations, and unlike its human counterpart may actually encode an active enzyme. Hyal-1 is the only hyaluronidase in mammalian plasma and urine, and is also found at high levels in major organs such as liver, kidney, spleen, and heart. A model is proposed suggesting that Hyal-2 and Hyal-1 are the major mammalian hyaluronidases in somatic tissues, and that they act in concert to degrade high molecular weight hyaluronan to the tetrasaccharide. Twenty-kDa hyaluronan fragments are generated at the cell surface in unique endocytic vesicles resulting from digestion by the glycosylphosphatidyl-inositol-anchored Hyal-2, transported intracellularly by an unknown process, and then further digested by Hyal-1. The two beta-exoglycosidases, beta-glucuronidase and beta-N-acetyl glucosaminidase, remove sugars from reducing termini of hyaluronan oligomers, and supplement the hyaluronidases in the catabolism of hyaluronan.
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PMID:The six hyaluronidase-like genes in the human and mouse genomes. 1173 Dec 67

This study investigates the effects of aestivation on body water content, body mass, acid mucopolysaccharide (AMPS) and some of its degrading enzymes in different tissues for some Australian desert frogs. The AMPS component of the liver, kidney, skin and cocoon alter during aestivation to help retain water, which is unchanged in most tissues of all frog species, and to protect the frogs from desiccation during extended periods of aestivation. Hepatic AMPS was unaltered in Cyclorana maini, C. platycephala and Neobatrachus sutor but increased significantly after 2 months of aestivation in C. australis. The level of AMPS in the kidney was elevated in all four frog species after 5 months of aestivation. Skin AMPS content in the skin of awake frogs decreases with aestivation period and increases in the cocoon. AMPS in the cocoon probably works as a cement between the cocoons' layers and its physical presence presumably contributes to preventing water flux. Changes in AMPS content in different tissues were accompanied by significant changes in both hyaluronidase and beta-glucuronidase activities, which play an important role in AMPS metabolism. Alcian blue staining of control and digested skin of C. australis and C. platycephala with testicular hyaluronidase indicated the presence of AMPS, concentrated in a thin layer (called ground substance, GS) located between stratum compactum and stratum spongiosum, and acid mucin concentrated in the mucous glands and in a 'tubular' structure which could be observed in the epidermal layer. Hyaluronidase digestion of the cocoon slightly changed the Alcian Blue colour, suggesting the presence of a large amount of acid mucin similar to that found in the skin mucous gland. The results of this study present data for the redistribution of AMPS, which may help in reducing water loss across the cocoon and reabsorption of water in the kidney during aestivation.
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PMID:Water content, body weight and acid mucopolysaccharides, hyaluronidase and beta-glucuronidase in response to aestivation in Australian desert frogs. 1189 99

We found a novel human gene (GenBank accession number, Kazusa DNA Research Institute KIAA1402) that possesses homology with chondroitin synthase. The full-length open reading frame consists of 772 amino acids and encodes a typical type II membrane protein. This enzyme had a domain containing beta 3-glycosyltransferase motifs, which might be a beta3-glucuronyltransferase domain, but no domain with beta 4-glycosyltransferase motifs, although both are found in chondroitin synthase. The putative catalytic domain was expressed in COS-7 cells as a soluble enzyme. Its glucuronyltransferase activity was observed when chondroitin and chondroitin sulfate polysaccharides and oligosaccharides were used as acceptor substrates. However, it was not detected when dermatan sulfate, hyaluronan, heparan sulfate, heparin, N-acetylheparosan, lactosamine tetrasaccharide, and linkage tri- and tetrasaccharide acceptors were employed. The reaction product, which was speculated to exhibit a GlcA beta 1-3GalNAc linkage structure at its non-reducing terminus, showed the following characteristics. 1) It was catabolized by beta-glucuronidase. 2) It was an acceptor for Escherichia coli K4 chondroitin polymerase (K4 chondroitin polymerase). 3) The product of K4 chondroitin polymerase was cleaved by chondroitinase ACII. On the other hand, no N-acetylgalactosaminyltransferase activity was detected toward any acceptors. Quantitative real time PCR analysis revealed that its transcripts were highly expressed in the placenta, small intestine, and pancreas, although they were ubiquitously expressed in various tissues and cell lines. This enzyme could play a role in the synthesis of chondroitin sulfate as a glucuronyltransferase.
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PMID:Molecular cloning and characterization of a novel chondroitin sulfate glucuronyltransferase that transfers glucuronic acid to N-acetylgalactosamine. 1214 78

Hyaluronan is a negatively charged, high molecular weight glycosaminoglycan found predominantly in the extracellular matrix. Intracellular locations for hyaluronan have also been documented in cytoplasm, nucleus, and nucleolus. The polymer has an extraordinarily high rate of turnover in vertebrate tissues. The focus here is to formulate a metabolic pathway for hyaluronan degradation using all available data, including the recently acquired information on the hyaluronidase gene family. Such a catabolic scheme has defied explication up to now. In somatic tissues, stepwise processing occurs, from the extracellular high molecular weight space filling, antiangiogenic approximately 107-kDa polymer, to intermediate sized highly angiogenic, inflammatory, and immune-stimulating fragments, and ultimately to tetrasaccharides that are antiapoptotic and potent inducers of heat-shock proteins. It is proposed that the high molecular weight extracellular polymer is tethered to the cell surface by the combined efforts of hyaluronan receptors and hyaluronidase-2 (Hyal-2). The hyaluronan is cleaved to a 20-kDa intermediate-sized fragment, the limit product of Hyal-2 digestion. These fragments are delivered to endosomal- and ultimately lysosomal-like structures. Further catabolism occurs there by Hyal-1, coordinated with the activity of two lysosomal beta-exoglycosidases, beta-glucuronidase and beta-N-acetyl-glucosaminidase. A membrane-associated mini-organelle is postulated, the hyaluronasome, in which coordinated synthetic and catabolic enzyme reactions occur. The hyaluronasome can respond to the physiological states of the cell by a series of membrane-bound and soluble hyaluronan-associated receptors, binding proteins, and cofactors that trigger enzymatic events and signal transduction pathways. These in turn can be modulated by the amounts and sizes of the hyaluronan polysaccharides generated in the catabolic cascade. Most of these highly dynamic interactions remain to be determined. It is also proposed that malignant cells can commandeer some of these interactions for facilitating tumor growth and spread.
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PMID:Devising a pathway for hyaluronan catabolism: are we there yet? 1451 8

Hyaluronidases are endo-glycosidases that degrade both hyaluronan (hyaluronic acid) (HA) and chondroitin sulfates. Deficiency of hyaluronidase activity has been predicted to result in a phenotype similar to that observed in mucopolysaccharidosis (MPS). In the present study, we surveyed a variety of patients with phenotypes similar to those observed in MPS, but without significant mucopolysacchariduria to determine if some are based on aberrations in serum hyaluronidase (Hyal-1) activity. The study included patients with well-characterized dysmorphic disorders occurring on genetic basis, as well as those of unkown etiology. The purpose of the study was to establish how wide spread were abnormalities in levels of circulating Hyal-1 activity. A simple and sensitive semi-quantitative zymographic procedure was used for the determination of activity. Levels of both beta-N-acetylglucosaminidase and beta-glucuronidase whose activities contribute to the total breakdown of hyaluronan (HA) were also measured, as well as the concentration of circulating HA. Among 48 patients with bone or connective tissue abnormalities, low levels of Hyal-1 activity were found in six patients compared to levels in 100 healthy donors (2.0-3.2 units/microL vs 6(+/- 1 SE) units/microL). These six patients exhibited a wide spectrum of clinical abnormalities, in particular shortened extremities: they included three patients with unknown causes of clinical symptoms, one patient with Sanfilippo disease, one of the seven patients with achondroplasia, and one with hypophosphotemic rickets. Normal levels of serum Hyal-1 activities were found in patients with Morquio disease, GM1 gangliosidosis, I cell-disease, 6 of the 7 patients with achondroplasia, Marfan's-syndrome and Ehlers-Danlos syndrome. No patient totally lacked serum Hyal-1 activity. Serum HA concentration was elevated in patients with Sanfilippo A and I-cell disease. Determination of serum and leukocyte Hyal-1 and serum HA may be useful to evaluate patients with metabolic and morphogenetic disorders.
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PMID:Serum hyaluronidase aberrations in metabolic and morphogenetic disorders. 1631 83

1. Nine acid hydrolases, cytochrome oxidase, alkaline phenylphosphatase and catalase were demonstrated in 0.25m-sucrose homogenates of newborn-rat calvaria. The acid hydrolases were: acid phenylphosphatase, acid beta-glycerophosphatase, beta-glucuronidase, beta-N-acetylglucosaminidase (beta-N-acetylaminodeoxyglucosidase), acid ribonuclease and acid deoxyribonuclease, showing optimum activity at about pH5; cathepsin, beta-galactosidase and hyaluronidase, with optimum activity at about pH3.6. 2. The main kinetic characters of these enzymes have been studied and methods for their quantitative assay have been worked out. The activities present in bone are given and compared with those found in liver. 3. Acid-phosphatase activity was assayed with phenyl phosphate and beta-glycerophosphate as substrates: activities with these two substrates appeared to be due to two different enzymes. Acid phenylphosphatase is particularly labile and is readily inactivated by various physical or chemical agents.
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PMID:Studies on bone enzymes. The assay of acid hydrolases and other enzymes in bone tissue. 1674 42

In the K/BxN mouse model of rheumatoid arthritis, autoantibodies specific for glucose-6-phosphate isomerase (GPI) can transfer joint-specific inflammation to most strains of normal mice. Binding of GPI and autoantibody to the joint surface is a prerequisite for joint-specific inflammation. However, how GPI localizes to the joint remains unclear. We show that glycosaminoglycans (GAGs) are the high affinity (83 nm) joint receptors for GPI. The binding affinity and structural differences between mouse paw/ankle GAGs and elbows/knee GAGs correlated with the distal to proximal disease severity in these joints. We found that cartilage surface GPI binding was greatly reduced by either chondroitinase ABC or beta-glucuronidase treatment. We also identified several inhibitors that inhibit both GPI/GAG interaction and GPI enzymatic activities, which suggests that the GPI GAG-binding domain overlaps with the active site of GPI enzyme. Our studies raise the possibility that GAGs are the receptors for other autoantigens involved in joint-specific inflammatory responses.
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PMID:High affinity glycosaminoglycan and autoantigen interaction explains joint specificity in a mouse model of rheumatoid arthritis. 1894 58


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