Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The optimal reaction conditions and kinetic properties of eleven leukocyte acid hydrolases determined with the use of fluorigenic derivatives of 4-methyl-umbelliferone are described. The enzymes studied were acid phosphatase, aryl sulfatase, alpha- and beta-glucosidase, alpha- and beta-galactosidase, alpha-mannosidase, N-acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucuronidase and alpha-fucosidase. More than 90% of the activity of each enzyme was released into a 27,000 X g supernatant by a double sonication procedure employing 0.9% sodium chloride and 0.1% Triton X-100. The Km values obtained were similar to those previously reported for chromogenic subtrates. A single Km value could not be derived for beta-galactosidase because its double reciprocal plot was not linear. All enzymes could be measured with less than 10 mug of protein within 15 min. Activators and inhibitors studied included the chloride salts of Na+, K+, Zn2+, Ca2+, Mg2+, Hg2+, and Fe2+ as well as p-chloromercuriphenysulfonate, glutathione, BAL, EDTA, EGTA, Triton X-100 and sodium taurocholate. The reaction conditions described in this report can be used for the diagnosis of various lysosomal storage diseases and should facilitate the development of automated procedures for the analysis of these eleven enzyme activities with small quantities of blood.
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PMID:Human leukocyte acid hydrolases: characterization of eleven lysosomal enzymes and study of reaction conditions for their automated analysis. 0 26

Endo-beta-galactosidase was purified 4400-fold from a culture filtrate of Escherichia freundii with 45% recovery. The enzyme preparation was practically free of exoglycosidases, sulfatase, and proteases. This enzyme hydrolyzed several keratan sulfates, endoglycosidically releasing oligosaccharides of various molecular sizes. Among the digestion products of the corneal keratan sulfate, the structure of a disaccharride and a tetrasaccharride were shown to be 2-acetamido-2-deoxy-6-O-sulfo-beta-D-glucosyl-(1 leads to 3)-D-galactose and 2-acetamido-2-deoxy-6-O-sulfo-beta-D-glucosyl-(1 leads to 3)-6-O-sulfo-beta-D-galactosyl-(1 leads to 4)-2-acetamido-2-deoxy-6-O-sulfo-beta-D-glucosyl-(1 leads to 3)-D-galactose, respectively. These oligosaccharide structures indicate that this enzyme specifically hydrolyzes the galactosidic bonds in which nonsulfated galactose residues participate. The enzyme could also hydrolyze a small oligosaccharide such as lacto-N-neotetraitol as follows: Gal(beta 1 leads to 4)GlcNAc(beta 1 leads to 3)Gal(beta 1 leads to 4) sorbitol leads to Gal(beta 1 leads to 4)GlcNAc(beta 1 leads to 3)Gal + sorbitol AB active blood group substance could be hydrolyzed by this enzyme only after Smith degradation. After enzymatic digestion small oligosaccharides and resistant macromolecules were produced. These findings indicate that the enzyme should be useful in studying the precise structures of keratan sulfates, related glycoproteins, and oligosaccharides.
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PMID:Endo-beta-galactosidase of Escherichia freundii. Purification and endoglycosidic action on keratan sulfates, oligosaccharides, and blood group active glycoprotein. 13 62

A 6-sulfatase specific for sugasr of the galactose configuration was purified 81-fold from the crude extract of Actinobacillus sp. IFO-13310. This preparation contained activity towards both N-acetylgalactosamine 6-sulfate and galactose 6-sulfate (relative activity, 2.4 : 1). The enzyme also release inorganic sulfate from the non-reducing galactose 6-sulfate end group of a trisaccharide disulfate prepared from keratan sulfate by sequential degradation with endo-beta-galactosidase, N-acetylglucosamine-6-sulfatase and exo-beta-N-acetylglucosaminidase. In addition, a tetrasaccharide trisulfate bearing the non-reducing N-acetylglucosamine 6-sulfate end group, also enzymatically prepared from keratan sulfate, was degraded to give rise to inorganic sulfate, N-acetylglucosamine and galactose by the sequential action of this enzyme, N-acetylglucosamine-6-sulfatase, exo-beta-N-acetylglucosaminidase and exo-beta-galactosidase (Charonia lampas).
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PMID:Galactose-6-sulfatase from Actinobacillus sp. IFO-13310 and its action on sulfated oligosaccharides from keratan sulfate. 15 51

A 14-year-old white girl with mild dysostosis multiplex, odontoid hypoplasia, short stature, cloudy corneas, keratansulfaturia, but without detectable central nervous system abnormalities was referred with the diagnosis of Morquio syndrome. Clinical and roentgenographic findings were minimal compared to those of typical patients with the Morquio syndrome, MPS IV. Beta-Galactosidase activity in extracts of the patient's cultured fibroblasts was deficient, while that of galactosamine-6-sulfate sulfatase was normal. Conjunctival biopsy revealed intracytoplasmic vacuoles typical of lysosomal storage diseases. It is postulated that in this patient the deficiency of a beta-galactosidase is responsible for inadequate degradation of keratan sulfate and the appearance of a mild form of the Morquio syndrome (MPS IVB).
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PMID:Morquio-like syndrome with beta galactosidase deficiency and normal hexosamine sulfatase activity: mucopolysacchariodosis IVB. 41 14

A female child of healthy, unrelated parents presented at 12 months of age with a history of moderately severe developmental delay, macrocephaly, dysmorphic facies, hypotonia, hepatosplenomegaly, mild generalized dysostosis multiplex, mucopolysacchariduria (dermatan and heparan sulfates), and Alder-Reilly bodies in peripheral blood leukocytes. Iduronate sulfatase activity in plasma was markedly depressed: 0.11 units/ml/h (normal, 1.75 +/- 0.56, N = 6). Analyses of arylsulfatases A, B, and C, heparan N-sulfatase, alpha-mannosidase, beta-mannosidase, beta-glucuronidase, beta-hexosaminidase, beta-galactosidase, and alpha-fucosidase activities in plasma, leukocytes, and/or cultured skin fibroblasts were all normal. Urinary sulfatide excretion was also within normal limits. Karyotypes of peripheral blood leukocytes and cultured skin fibroblasts were normal. Serum iduronate sulfatase activities in the parents were in the normal range (father, 1.63 units/ml/h; mother, 1.25 units/ml/h). The results of analyses of restriction fragment length polymorphisms (RFLP) of DNA from cultured skin fibroblasts with the use of probes for loci extending from Xpter to Xq28 showed X chromosome heterozygosity and confirmed the paternal origin of one of the X chromosomes. Studies on sulfur-35 uptake in mixed fibroblast cultures showed cross-correction of [35S]-glycosaminoglycan accumulation between cells from the patient and normal cells or cells from a patient with Hurler disease; however, there was no cross-correction between cells from the patient and those from boys affected with classical Hunter disease. This represents only the second confirmed case of Hunter disease reported in a karyotypically normal girl.
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PMID:Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl. 211 88

The existence of lysosomes and acid hydrolase activity was demonstrated in an in vitro blood-brain barrier (BBB) model comprising primary cultures of bovine brain microvessel endothelial cell (BMEC) monolayers. BMEC lysosomes were observed by the uptake of acridine orange and fluorophore-labeled acetylated low-density lipoprotein by fluorescence microscopy. Cytochemical localization of the acid hydrolase, sulfatase, and acid phosphatase (AcP) activities with light microscopy also revealed hydrolase-positive vacuoles or lysosomes that varied in number from cell to cell. BMEC monolayers were fractionated and biochemical assays of the sulfatase, AcP, and beta-galactosidase were performed. Significant activities of the acid hydrolases were found to be associated with lysosome and microsome fractions (69-77%). The majority of beta-galactosidase (approximately 48%) and total sulfatase (approximately 58%) activity was associated with the lysosome fraction of the BMECs. In contrast, approximately 52% of AcP activity was associated with the microsome fraction of the cells. The results of this study are consistent with the demonstration in vivo of acid hydrolases as potential factors in the endocytic pathway for transport of proteins through the BBB and as contributors to the BBB's enzymatic barrier function.
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PMID:Demonstration of acid hydrolase activity in primary cultures of bovine brain microvessel endothelium. 249 11

Urine specimens from two sibs affected with cerebroside sulfatase activator deficiency were examined to ascertain whether the deficiency of the supplementary activator protein required for the enzymatic hydrolysis of cerebroside sulfate was also evident in urine. Material from chromatographic fractionations was examined for the activator activity to avoid ambiguities resulting from protein inhibition. There were substantial deficits in all chromatographic fractions corresponding to activator-containing fractions of control urines. Since patient urines contained elevated amounts of lactosylceramide, digalactosylceramide, and globotriaosylceramide and since similarities between activators for cerebroside sulfate and GM1 ganglioside hydrolyses had been noted previously, the chromatographic fractions were also examined for activators in other glycosphingolipid hydrolase systems. There was coincidence of activators for the GM1 ganglioside/beta-galactosidase and the globotriaosylceramide/alpha-galactosidase A reactions with the cerebroside sulfatase activator in control urine fractions, and the patients' urines were deficient in activator activities for the three reactions. Identity of the three activators was suggested and antiserum to purified GM1 ganglioside activator was used to test this possibility. There were depressed levels of cross-reacting material in fractions of patient urines by Ouchterlony double diffusion and in unfractionated urine by enzyme-linked immunosorbent assay. Purified activators for the cerebroside sulfate and GM1 ganglioside systems showed lines of identity with no spurring on Ouchterlony double diffusion, identical mobility on immunoelectrophoresis, and similar stimulatory activities toward hydrolysis of the three glycosphingolipid species by their respective enzymes. Finally, the three activator activities were retained by anti-GM1-activator IgG coupled to Sepharose 4B. The results suggest strongly that the same protein entity serves as activator for the enzymatic hydrolysis of cerebroside sulfate, GM1 ganglioside, and globotriaosylceramide.
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PMID:Activator protein required for the enzymatic hydrolysis of cerebroside sulfate. Deficiency in urine of patients affected with cerebroside sulfatase activator deficiency and identity with activators for the enzymatic hydrolysis of GM1 ganglioside and globotriaosylceramide. 298 75

Further clinical heterogeneity of Morquio disease, mucopolysaccharidosis IV (MPS IV), is delineated by the observation of a 30-year-old man with unusually mild clinical manifestations. He is 156 cm tall, has comparatively mild skeletal abnormalities and fine corneal deposits. Keratosulfaturia is absent. N-Acetylgalactosamine-6-sulfate (GalNAc-6-S) sulfatase (E.C. 3.1.6.-) was markedly reduced in his fibroblasts. The residual enzyme activity exhibited a pH profile comparable to that of patients with the "classical" form of the disorder. From our observation and a review of the literature it is concluded that Morquio disease can be divided in several subgroups: besides the severe ("classical") type A there exist an intermediate and a mild form that are also caused by a GalNAc-6-S sulfatase deficiency. A late-onset variant of Morquio disease, which is due to a deficiency of beta-galactosidase, has been classified as type B. In addition, patients with mild manifestation of the disease and normal activities in fibroblasts of GalNAc-6-S sulfatase and beta-galactosidase have been observed (type C). The genetic nature of the broad clinical variability of Morquio disease is incompletely understood: it is partially caused by different enzyme defects. Other factors thought to influence the clinical expression include the pH profile of the residual enzyme activity and an additional neuraminidase defect.
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PMID:Heterogeneity of Morquio disease. 308 64

Activator protein for galactosylceramide sulfatase (GSase) was purified from human liver. The activator has an approximate molecular weight of 22,000, is glycoprotein in nature, and is most probably a trimer consisting of an 8,000 dalton monomer. Monospecific rabbit antiserum raised against the activator strongly inhibited the activity of the activator. In the presence of a 10-fold or more excess of galactosylceramide sulfate (GS) on a molar basis, GS binding to the GSase activator occurred, and was saturated at an equimolar ratio. Binding studies on the GSase activator were conducted using affinity chromatography on derivatives of GS as ligands, and gel filtration of mixtures containing glycolipids and the activator. A "GS-acid" derivative, which was prepared by oxidative cleavage of sphingosine moiety in GS, and a sulfonamide derivative of GS as ligands still retained affinity for the GSase activator, while a hydrophobic ligands, an aminohexyl group did not bind completely the activator. A ligand of "galactosylceramide-acid" had weak affinity for GSase activator. These results suggest that the sulfate group and one of the two hydrocarbon chains in GS are not essential for the binding of the activator. The affinity of galactosylceramide for the GSase activator was confirmed by the detection of the lipid-protein complex on gel filtration. The activator weakly stimulated porcine GM1-beta-galactosidase activity.
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PMID:Purification and properties of galactosylceramide sulfatase activator from human liver. 408 63

Sphingolipidoses are an heterogeneous group of inherited disorders of lipid metabolism affecting primarily the central nervous system. These disorders occur chiefly in the pediatric population, and the degenerative nature of the disease processes is generally characterized by diffuse and progressive involvement of neurones (gray matter) with psychomotor retardation and myoclonus or of fiber tracts (white matter) with weakness and spasticity. Biochemical research has identified the defects in the sphingolipidoses to specific lysosomal enzymes. For example, Niemann-Pick disease lacks sphingomyelinase; Krabbe's disease lacks galactocerebrosidase; Gaucher's disease lacks beta-D-glucosidase; metachromatic leukodystrophy lacks sulfatase; Tay-Sachs disease lacks hexosaminidase A; and generalized gangliosidosis lacks beta-galactosidase. Although there are no currently available modes of rendering corrective therapy in these disorders, a definitive diagnosis is possible both antepartum as well as postpartum. This information provides a sound and accurate basis for genetic counseling.
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PMID:Sphingolipidoses. 555 2


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