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)

Isoelectric focusing was used to study the multiple forms of acid phosphatase, arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase in lysosomes isolated from rat kidney. The isoelectric points of the main protein and hydrolase peaks were 1-1.5 units lower when electrofocusing was done in a pH 3-10 gradient than in a pH 10-3 gradient, apparently because the lysosomal constituents aggregated strongly at their isoelectric points and tended to settle somewhat in the gradient due to gravity. In the extended pH gradient the acidic form of each hydrolase occurred as asingle, relatively discrete peak. However, when pooled acidic fractions were refocused in a restricted pH gradient (pH 6-3 or 3-5) multiple acidic enzyme and protein components were resolved with isoelectric points between 2.7 and 5.1. When autolysis was minimized by extracting lysosomal fractions at alkaline pH (0.2% Triton X-100, 0.1%p-nitrophenyloxamic acid, 0.1 M glycine buffer, pH9) and including 0.1%p-NITROPHENYLOXAMIC ACID, AN INHIBITOR OF LYSOSOMAL NEURAMINIDASE AND CATHEPSIN D, in the pH gradient, arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase occurred in two forms, an acidic form with an isoelectric point of about 4.4, and a basic form with an isoelectric point close to 6.2, 6.7 and 8.0, respectively. Acid phosphatase occurred in three forms with isoelectric points of 4.1, 5.6 and 7.4. When some autolytic digestion was permitted by extracting lysosomal fractions in an acidic medium (0.2% Triton X-100, 0.1 M sodium acetate buffer, pH 5.2) AT 0-4DEGREES C and omitting p-nitrophenyloxamic acid from the gradient, the acidic form of beta-glucuronidase and the intermediate form of acid phosphatase were lost, the isoelectric points of the acidic forms of acid phosphatase, arylsulfatase and beta-N-acetylhexosaminidase were increased 0.6-1.2 units, and the isoelectric point of the basic forms of acid phosphatase, arylsulfatase and beta-glucuronidase was increased 0.5 unit. When lysosomal extracts were incubated with bacterial neuraminidase before electrofocusing, the acidic forms of acid phosphatase, arylsulfatase and beta-glucuronidase were largely lost, the isoelectric point of the acidic form of beta-N-acetylhexosaminidase was increased from 4.5 to 6.4, and the isoelectric points of the basic forms of all four hydrolases were increased 0.5-1.5 units. Autoincubation of lysosomal extracts in vitro at pH 5.2 PRODUCED SIMILAR, THOUGH LESS MARKED, effects. cont'd
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PMID:Isoelectric-focusing behavior of acid hydrolases in rat kidney lysosomes. Effects of the pH gradient, autolysis and neuraminidase. 23 55

Isoelectric focusing was used to investigate the multiple forms of acid phosphatase, arylsulfatase, beta-glucuronidase, beta-galactosidase and beta-N-acetylhexosaminidase in the following, previously characterized subcellular fractions from rat kidney: a special rough microsomal fraction, enriched up to 9-fold over the homogenate in acid hydrolases; a smooth microsomal fraction; a Golgi membrane fraction enriched about 2.5-fold in acid hydrolases and 10- to 20-fold in several glycosyl transferases; and a lysosomal fraction enriched up to 25-fold in acid hydrolases. The electro-focusing behavior of the hydrolases in these fractions was markedly sensitive to the autolytic changes that occur under acidic conditions, even at 4 degrees C. Autolysis was minimized by extracting fractions in an alkaline medium (0.2% Triton X-100, 0.1 M sodium glycinate buffer, pH 10, 0.1 % p-nitrophenyloxamic acid) and adding p-nitrophenyloxamic acid (0.1 %), AN INHIBITOR OF LYSOSOMAL NEURAMINIDASE AND cathepsin D, to the pH gradient. The enzymes in the lysosomal fraction displayed a characteristic bimodal or trimodal distribution. Arylsulfatase, beta-glucuronidase and beta-N-acetylhexosaminidase occurred in an acidic form with an isoelectric point of 4.4, and a basic form with an isoelectric point of 6.2, 6.7 and 8.0, respectively. Acid phosphatase and beta-galactosidase occurred in an acidic, intermediate and basic form with isoelectric points of about 4. 1, 5.6 and 7.4, respectively. In the special rough microsomal fraction these enzymes were mostly in a basic form with isoelectric points between 7.5 and 9; these were 1-2 units higher than the corresponding basic forms in the lysosomal fraction. Treatment of extracts of the rough microsomal fraction with bacterial neuraminidase raised the isoelectric points of all five hydrolases by 1-2.5 units, indicating the presence of some N-acetylneuraminic acid residues in these basic glycoenzymes. The hydrolases in the Golgi fraction were largely in an acidic form with isoelectric points similar to or lower than those of the corresponding acidic components in the lysosomal fraction. The hydrolases in the smooth microsomal fraction showed isoelectric-focusing patterns intermediate between those in the rough microsomal and the Golgi fractions. These findings support the following scheme for the synthesis, transport and packaging of the lysosomal enzymes. Each hydrolase is synthesized in a restricted portion of the r
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PMID:Changes in electronegativity of lysosomal hydrolases during intracellular transport. An isoelectric-focusing study in subcellular fractions of rat kidney. 23 56

A potential enzymic mechanism for the degradation of glycosaminogly cans was characterised using enzymes found in rheumatoid synovial fluid from the knee joint. This mechanism involves a true hyluronidase together with the concerted action of beta-glucuronidase and beta-N-acetylhexosaminidase. The contribution of the exopolysaccharidases to hyaluronate degradation was demonstrated by the use of specific inhibitors, while the distinct identity of a true hyaluronidase was shown by ammonium sulphate and agarose gel column fractionations. Only the hyluronidase fraction was capable of degrading high molecular weight hyaluronate. The exopolysaccharidase activities were shown to be markedly elevated in rheumatoid as compared to osteoarthritic synovial fluid and also normal serum. On the other hand, hyluronidase was similarly active in rheumatoid and osteoarthritic synovial fluids; both these levels were lower than that of normal human serum. Hyaluronidase in synovial fluid may thus be derived by diffusion from serum, since it is of relatively low molecular weight (60 000). The pH requirements of this enzyme system and the strong inhibition of hyaluronidase by synovial fluid make it unlikely that the mechanism operates extracellularly. It is proposed that as a lysosomal mechanism, however, it is an important contributing factor in the chronic erosion process characteristic of rheumatoid arthritis.
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PMID:The characterisation and function of the polysaccharidases of human synovial fluid in rheumatoid and osteoarthritis. 23 48

Fibroblasts were incubated in the presence of the anti-microtubular drugs colchicine, vinblastine and vincristine. In concentrations between 10nm and 1 mM these drugs stimulated the secretion of beta-N-acetylglucosaminidase, alpha-N-acetylglucosaminidase and beta-glucuronidase, but not of beta-galactosidase. The endocytosis of beta-N-acetylhexosaminidase and alpha-N-acetylglucosaminidase, but not of beta-glucuronidase, was inhibited at drug concentrations higher than 0.1 micrometer. Formation, secretion and association with the cell membrane of sulphated proteoglycans were not affected by anti-microtubular drugs. Endocytosis of sulphated proteoglycans and their subsequent degradation was inhibited by drug concentrations above 0.1 micrometer. The inhibition of intracellular glycosaminoglycan degradation led to a moderate storage of these compounds. These results suggest that microtubules participate in the control of secretion and endocytosis of lysosomal enzymes, and in the endocytosis and degradation of lysosomal substrates such as sulphated proteoglycans.
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PMID:Studies on secretion and endocytosis of macromolecules by cultivated skin fibroblasts. Effects of anti-microtubular agents on secretion and endocytosis of lysosomal hydrolases and of sulphated glycosaminoglycans. 63 45

The dodecasaccharide obtained by treating dermatan sulfate with testicular hyaluronidase, chondroitinase AC, and beta-glucuronidase was incubated with diluted, normal human serum at pH 4.5 or 7.0 followed by chondro-4-sulfatase at pH 7.0. Analyses of the reaction products indicate release of hexosamine but not further degradation of the substrate. It is concluded that normal human serum possesses an exo-beta-N-acetylhexosaminidase active on dermatan sulfate.
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PMID:Beta-N-acetylhexosaminidase active on dermatan sulfate. 109 49

Normal N-acetylglucosamine 1-phosphotransferase activity toward mono- and oligosaccharide acceptor substrates was detected in cultured skin fibroblasts from mucolipidoses II and III patients who were designated as variants (one of four mucolipidosis II and three out of six mucolipidosis III patients examined). The activity toward natural lysosomal protein acceptors was absent or deficient in cell preparations from all patients with classical as well as variant forms of mucolipidoses II and III. Complementation analysis, using fused and cocultivated mutant fibroblast combinations, revealed that, while cell lines with variant mucolipidosis III constituted a complementation group distinct from that of classical forms of mucolipidoses II and III, the variant mucolipidosis II cell line belonged to the same complementation group as did the classical forms. In contrast to the mutant enzyme from variant mucolipidosis III patients that failed to recognize lysosomal proteins as the specific acceptor substrates, the activity toward alpha-methylmannoside in the variant mucolipidosis II patient could be inhibited by exogenous lysosomal enzyme preparations (bovine beta-glucuronidase and human hexosaminidase A). These findings suggest that N-acetylglucosamine 1-phosphotransferase is composed of at least two distinct polypeptides: (1) a recognition subunit that is defective in the mucolipidosis III variants and (2) a catalytic subunit that is deficient or altered in the classical forms of mucolipidoses II and III as well as in the mucolipidosis II variant.
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PMID:Mucolipidoses II and III variants with normal N-acetylglucosamine 1-phosphotransferase activity toward alpha-methylmannoside are due to nonallelic mutations. 130 24

Marine mussels (Mytilus edulis, a bivalve mollusc) are increasingly used as environmental sentinels in pollution biomonitoring. Pathological reactions of the lysosomal system in hepatopancreatic cells have proven to be sensitive bioindicators of pollutant effect. However, if such reactions are to be used as biomarkers, then they must be clearly distinguishable from any hormonally-induced changes linked to normal seasonal activity such as the reproductive cycle. The aim of the present study was to test the effects of several cell-to-cell signalling compounds on the lysosomes of the hepatopancreatic digestive cells. In vitro incubation of tissue slices showed that epinephrine, acetylcholine and prostaglandin F2 alpha reduced lysosomal membrane stability and latency of beta-N-acetylhexosaminidase and beta-glucuronidase. These results indicate the presence of cell surface receptors for all three hormones. The observed changes in lysosomal fragility were less pronounced than those induced by pollutants and when considered together with other published data, indicate that hormonal regulation of digestive cell lysosomes is unlikely to pose a problem for the use of lysosomal reactions as biomarkers for chemical insult.
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PMID:Lysosomal changes in the response of molluscan hepatopancreatic cells to extracellular signals. 183 69

Oligosaccharides of a non-oligomannoside type were released from porcine alpha-mannosidase by hydrazinolysis, and were fractionated into at least 15 homogeneous oligosaccharides. Most of them are oligosaccharides with galactose and N-acetylglucosamine residues attached to a common core, alpha Man2 beta Man beta GlcNAc(+/- alpha-L-Fuc)beta GlcNAc. About 50% of the oligosaccharides contain one or two outer chains composed of one beta-linked N-acetylglucosamine and two beta-linked galactose residues attached to the core portions, and the others seem to be metabolic intermediates. Based on the results of studies on the binding of alpha-mannosidase to RCA (Ricinus communis agglutinin) I-agarose and MBP (mannan-binding protein)-Sepharose, which are specific for glycoproteins possessing N-acetyllactosamine-type and oligomannoside-type (including oligomannosides with N-acetylglucosamine at the reducing termini) oligosaccharides, respectively, about 85% of the enzyme molecules were found to have both types of oligosaccharides. Similarly, it was shown that of the several acid hydrolases present in the lysosomes purified from rat liver, only alpha-mannosidase has both types of oligosaccharides, and the greater parts of beta-glucuronidase, acid phosphatase and beta-N-acetylhexosaminidase seem to have only oligomannoside-type oligosaccharides.
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PMID:Structures of galactose-containing oligosaccharides of alpha-mannosidase from porcine kidney. 309 80

A method was developed for the analysis of non-reducing terminal structure of radiolabelled chondroitin sulphate chains with the aid of N-acetylgalactosamine 4-sulphatase ('terminal 4-sulphatase'), N-acetylgalactosamine 6-sulphatase ('terminal 6-sulphatase'), beta-glucuronidase and beta-N-acetylhexosaminidase. Studies with this method on the non-reducing terminal structure of [35S]sulphate- and [3H]glucose-labelled chondroitin sulphate chains from rat and chick-embryo cartilages showed that the presence of a high proportion of 4-sulphated hexosamine residues is a common feature of the termini of newly synthesized chondroitin sulphate chains. Of the non-reducing terminal 4-sulphated hexosamine residues, about 14% (chick embryo) or 46% (rat) contained an additional sulphate group at position 6. The internal portion of the chondroitin sulphate chains, in contrast, contained little or no 4,6-bis-sulphated hexosamine residue, suggesting that 4,6-bis-sulphated structure may play a role in biosynthetic control at the level of chain termination.
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PMID:A distinct terminal structure in newly synthesized chondroitin sulphate chains. 315 11

A panel of 42 rodent x cat somatic cell hybrids has been used to assign seven structural genes for lysosomal enzymes to specific chromosomes in the domestic cat. The assignments include alpha-glucosidase (GANAB) to chromosome D1, alpha-galactosidase (GLA) to the X chromosome, beta-galactosidase 1 (GLB1) to chromosome B3, beta-glucuronidase (GUSB) to chromosome E3, alpha-mannosidase A (MANA) to chromosome B3, alpha-L-fucosidase (FUCA) to chromosome C1, and hexosaminidase A (HEXA) to chromosome B3. In all cases, the feline lysosomal enzyme genes were located in linkage groups which were syntenic with their homologous positions in the human gene map. These assignments expand the genetic map of the cat and reaffirm the extensive syntenic homology between the chromosome maps of man and cat.
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PMID:Chromosomal mapping of lysosomal enzyme structural genes in the domestic cat. 322 Apr 74


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