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 two human brain beta-galactosidases were solubilized and fractionated by Sephadex G-200 gel filtration, free from each other. Substrate specificities of the two enzymes were examined for galactosylceramide, lactosyl-[N-stearoyl]ceramide, lactosyl-[N-lignoceroyl]ceramide, galactosyl-N-acetylgalactosaminyl-[N-stearoyl]ceramide, lactosyl-[N-lignoceroyl]ceramide, galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]galactosyl-glucosylceramide (GMI-ganglioside), galactosyl-N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM1-ganglioside), and 4-methylumbelliferyl beta-galactoside. Under appropriately optimized conditions, either of the two beta-galactosidases could hydrolyze all of the substrates, although with widely varying rates. Relative specific activities of galactosylceramide beta-galactosidase toward galactosylceramide, lactosyl-[N-steroyl]ceramide, lactosyl-[N-lignoceroyl]ceramide. GM1-ganglioside, asialo GM1-ganglioside, and 4-methylumbelliferyl beta-galactoside were 100, 510, 250, 39, 41 and 120, respectively. Relative specific activities of GM1-ganglioside beta-galactosidase toward the same series of the substrates were 0.3, 78, 19, 100, 150 and 240; However, the optimal assay conditions for any given natural substrate were sufficiently different for each beta-galactosidase so that diagnostic assays for the two genetic diseases due to beta-galactosidase deficiencies could be carried out in whole tissues. Since the relative distribution of the two enzymes vary greatly in different tissues, contributions by the two enzymes to degradation of the natural glycosphingolipids in vivo may well vary in different organs. These findings may have an important bearing on the biochemical pathogenesis of these genetic disorders.
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PMID:Substrate specificities of the two genetically distinct human brain beta-galactosidases. 1 10

Acid beta-D-galactosidases (EC 3.2.1.23) from human urine samples have been characterized using GM1-ganglioside, asialofetuin, and 4-MU-beta-D galactopyranoside. Sepharose 6-B column chromatography of crude urine supernatant fluids resolved three forms of acid beta-D-galactosidase activity with apparent molecular weights of 500 X 10(3)--700 X 10(3) (I), 90 X 10(3)--120 X 10(3) (II), and 20 X 10(3)--27 X 10(3) (III), which hydrolyzed 4-MU-beta-D-galactopyranoside, GM1-ganglioside and asialofetuin. The crude urine supernatant fluids and the separated forms of acid beta-D-galactosidase exhibited similar apparent KM values for the respective substrates. Starch gel electrophoresis of urine samples at pH 7.0 revealed a slow anodally migrating form of acid beta-D-galactosidase which electrophoretically corresponded to form I and a faster anodally migrating form corresponding to form II. Form III migrated as a composite of forms I and II suggesting that aggregation to the larger molecular weight activity forms occurred during starch gel electrophoresis. This report represents the first characterization of urinary acid beta-D-galactosidase with respect to naturally occurring glycolipid and glycoprotein substrates. In addition, data is presented to indicate that the enzyme may be composed of an enzymatically active form with an apparent molecular weight of 20 X 10(3)--27 X10(3), which is also capable of hydrolyzing the glycolipid and glycoprotein substrates.
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PMID:Characterization of the acid beta-D-galactosidases from human urine. 2 27

The activity of GM1 beta-galactosidase in the brain and liver of patients with GM1-gangliosidosis was assayed using GM1-ganglioside tritiated in the terminal galactose. In the cases of GM1-gangliosidosis Types 1 and 2A the activity was less than 0.5% of the control. In the liver of GM1-gangliosidosis Type 2B the activity was observed to be much higher than that of Types 1 and 2A. On Sephadex G-150 gel filtration, three active fractions (I, II and III) for 4-methylumbelliferyl beta-galactopyranoside (4MU) and two active fractions (I and II) for GM1-ganglioside were obtained in the control liver. There was no active fraction for GM1-ganglioside in spite of the preserved fraction I for 4MU in the liver of GM1-gangliosidosis Type 1 or Type 2A. In any of the three cases fraction II for both 4MU and G71-ganglioside was not detected.
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PMID:The abnormalities of beta-galactosidase in GM1-gangliosidoses. 2 79

Neutral beta-galactosidase was partially purified from liver of normal controls, a patient with Niemann-Pick disease type A and the previously described patient with lactosyl ceramidosis using Concanavalin A-Sepharose adsorption and Sephadex G-100 gel filtration. The partially purified fractions were essentially free of galactosyl ceramide beta-galactosidase and GM1 beta-galactosidase activities. The normal and Niemann-Pick fractions were found to hydrolyze lactosyl ceramide, in the presence of sodium taurodeoxycholate, at a pH optimum of 5.6 as well as aryl beta-galactosides and aryl beta-glucosides at pH 6.2. The corresponding fraction from the lactosyl ceramidosis liver contained only 1--4% of the normal activity towards artificial substrates and lactosyl ceramide. Cross-reacting material identical to the normal was demonstrated in this fraction with antiserum raised against purified neutral beta-galactosidase, but no activity was observed in the precipitin line when stained with naphthol AS-LC-beta-galactoside or naphthol AS-LC-beta-glucoside. A similar deficiency of neutral beta-galactosidase activity was demonstrated in cultivated fibroblasts of the patient with lactosyl ceramidosis. Following adsorption on Concanavalin A-Sepharose and anti-GM1 beta-galactosidase antibody-Sepharose conjugates and chromatography on DEAE cellulose, fibroblast lysates from the patient exhibited 3% of normal activity towards 4-methyl-umbelliferyl beta-glucoside at pH 6.2 and 12% of normal activity towards lactosyl ceramide at pH 5.6. These data suggest that neutral beta-galactosidase may have an in vivo role in the cleavage of lactosyl ceramide and that a deficiency of this activity may be related to the lactosyl ceramide accumulation observed in the patient with lactosyl ceramidosis.
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PMID:Lactosyl ceramidosis: deficient activity of neutral beta-galactosidase in liver and cultivated fibroblasts? 2 29

beta-Galactosidase activity was investigated in one case of juvenile GM1-gangliosidosis. This patient exhibited normal activity of the neutral form of beta-galactosidase (measured as beta-glucosidase activity) and normal pH curve of residual acid beta-galactosidase activity in leucocytes and fibroblasts. A shift towards more neutral pH optimum was seen in the beta-galactosidase enzyme occurring in serum. The communication also presents a study of the relationship of the different beta-galactosidases in human liver using isolated urine oligosaccharide from this patient as a beta-galactoside substrate. The other natural beta-galactoside substrates used in this investigation were different oligosaccharides, one glycopeptide and ceramide-beta-galactosidase. The beta-galactosidase forms with acidic pH optimum towards synthetic substrate (A forms) exhibit activity towards the natural substrate (except ceramide-beta-galactoside). The "neutral" beta-galactosidase with broad substrate specificity (B form) which includes beta-glucosides had no activity towards the natural substrates used. It could also be shown that the activity towards ceramide-beta-galactoside was a third type of beta-galactosidase different from A and B forms.
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PMID:beta-D-galactosidase activities in juvenile GM1-gangliosidosis. 3 Oct 52

The residual liver acid beta-galactosidase (beta-gal) activity from a case of feline GM1 gangliosidosis was partially purified and characterized with respect to its pH optimum, kinetic properties, thermostability, isoelectric point, molecular weight, and antigenicity. In comparison to the normal enzyme, the mutant enzyme had the same pH optima for the three substrates tested, a reduced Km for 4-methylumbelliferyl-beta-gal, elevated Km's for GM1 and asialofetuin (ASF), and increased thermolability. In addition, the mutant beta-gal had a higher isoelectric point, a reduced molecular weight, and appeared to be antigenically different from normal. The results suggest that the mutation in the Birmingham GM1 cat is structural and that the residual enzyme activity is a structurally altered acid beta-gal. The apparent lack of antigenic identity between the mutant and normal enzymes, in contrast to the situation in many human GM1 patients, is most unusual.
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PMID:Feline GM1 gangliosidosis: characterization of the residual liver acid beta-galactosidase. 8 95

A 28-month-old child was found to have several clinical features of lysosomal storage diseases, including: coarse facies, hepatosplenomegaly, lumbar kyphosis due to hypoplastic beaked L1 and L2 vertebral bodies, vacuolated lymphocytes in blood smears and rare foamy hystiocytes in bone marrow. However, no signs of neurological or ocular abnormalities were detected. A beta-galactosidase deficiency was demonstrated in leukocytes and cultured skin fibroblasts, with a residual activity toward 4-methylumbelliferyl-beta-galactopyranoside ranging between 5 and 15% of the normal mean. Normal activities were found for several other lysosomal acid hydrolases. beta-Galactosidase activities in leukocytes and cultured skin fibroblasts from both parents were within the normal ranges. The patient seems to represent an atypical expression of acid beta-galactosidase deficiency, since his clinical picture does not exaclty correspond to that of either the two classical types of GM1-gangliosidosis or other atypical patients reported in the literature havining beta-galactosidase deficiency.
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PMID:Atypical expression of beta-galactosidase deficiency in a child with Hurler-like features but without neurological abnormalities. 9 48

Uptake of radioactivity from 14C-galactose into gangliosides by cultured skin fibroblasts was studied. GM3 was the major ganglioside in control human fibroblasts. An increase of GM1 was demonstrated in GM1-gangliosidosis fibroblasts. The degree of GM1 accumulation was correlated with the clinical types of this disease. The fibroblasts from an infantile-type patient showed a marked increase of GM1. In late-onset types the amount of total gangliosides was only slightly increased, but the distribution of individual gangliosides was definitely abnormal; a relative increase of GM1 was demonstrated in these cases. GM1 beta-galactosidase activities were not detectable in either infantile or late-onset cases.
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PMID:GM1-gangliosidosis: accumulation of ganglioside GM1 in cultured skin fibroblasts and correlation with clinical types. 9 63

A prenatal diagnosis of GM1-gangliosidosis was made in a pregnancy at risk, on the basis of a deficiency of beta-galactosidase activity demonstrated in cultured amniotic fluid cells. Biochemical analyses were performed in the aborted fetus. GM1-ganglioside beta-galactosidase activity was reduced to 1% of the control value in both the brain and liver of the affected fetus. Lamellar bodies suggestive of membranous cytoplasmic bodies were found in cells of basal ganglions, while the accumulation of GM1-ganglioside in the brain was not remarkable.
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PMID:Prenatal diagnosis of GM1-gangliosidosis: biochemical manifestations in fetal tissues. 10 1

Cultured skin fibroblasts from a 2-year-old boy with an atypical form of beta-galactosidase deficiency have been studied. With the artificial substrate 4-methylumbelliferyl-beta-D-galactopyranoside, 5--15% residual activity was found in fibroblasts from this patient. Most of this activity was in the monomeric A form of the enzyme, very little in the multimeric B form. Km value, pH profile, and heat lability of the mutant enzyme were similar to those of beta-galactosidase from control fibroblasts. Immunological studies showed that the mutant enzyme cross-reacted with an antiserum raised against human liver beta-galactosidase, but the catalytic activity per unit antigenic activity was lower than normal. It was demonstrated by somatic cell hybridization that the gene mutation in this patient is different from that in patients with type 1 or type 2 GM1-gangliosidosis. No genetic complementation was found after fusion of fibroblasts from this patient with those from two other clinical variants of GM1-gangliosidosis formerly designated type 3 and adult type 4.
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PMID:A two-year-old patient with an atypical expression of GM1-beta-galactosidase deficiency: biochemical, immunological, and cell genetic studies. 10 14


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