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)

GM1-ganglioside hydrolysis by leukocytes and fibroblasts, tissues easily obtainable from patients, was investigated using 3H-labeled GM1 and was found to be at least as active as that reported for any other tissue. Sodium taurocholate was required for the reaction, the crude bile salt at an optimum concentration of 0.4% producing twice as much activity as pure taurocholate at its optimum concentration of 0.8%. Leukocyte GM1-ganglioside beta-galactosidase and 4-MU-beta-gal cleaving activities were similar, 134.5 +/- 23.3 and 179.8 +/- 25.4 nmol/h/mg protein, respectively. In cultured skin fibroblasts and amniotic fluid cells these enzyme activities were 4 to 5 times higher. Homozygotes for GM1-gangliosidosis showed negligible activity while in heterozygotes the leukocyte GM1-cleaving activity was reduced to one-third of control values. In leukocytes from patients with four other sphingolipid storage diseases the activity was either normal (Krabbe's, Tay-Sachs, Metachromatic leukodystrophy) or increased (adult Gaucher's).
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PMID:GM1-ganglioside beta-galactosidase in leukocytes and cultured fibroblasts. 41 12

A chromogenic substrate, 2-hexadecanoylamino-4-nitrophenyl-beta-D-galactopyranoside, has recently been described for the diagnosis of Krabbe's disease. Hydrolysis of this substrate by extracts of cultured cells and tissues was compared with the activities of lactocerebrosidase I and non-specific beta-galactosidase. Under appropriate conditions, hydrolysis of the chromogenic analogue was markedly reduced in extracts of cultured amniotic fluid cells and skin fibroblasts derived from cases of Krabbe's disease. Activity was also markedly deficient in extracts of Krabbe's brain, although only a partial reduction was measured in liver extracts. Generally activities were higher in tissues of fetal origion. Unfortunately, the new analogue proved less specific and less sensitive than the natural substrates used to diagnose Krabbe's disease. Consequently, the analogue does not provide a satisfactory alternative substrate for the prenatal diagnosis of Krabbe's disease.
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PMID:Use of a chromogenic substrate for the diagnosis of Krabbe's disease, with special reference to its application in prenatal diagnosis. 69 19

Metabolism of tritium-labelled galactosylceramide and lactosylceramide added to the culture medium was examined in cultured skin fibroblasts from 4 patients with globoid cell leukodystrophy (GLD) and 4 control individuals. The uptake of [3H]galactosylceramide and [3H]lactosylceramide by the fibroblasts continued actively at least up to 3 days. Approximately 30--40% of the galactosylceramide, which had been taken up, was released subsequently from the cells in a 4-day period, whereas only 10% of lactosylceramide was released during the same period. The GLD fibroblasts showed no abnormality in the kinetics of the uptake and in the release of these glycosphingolipids which are natural substrates of the beta-galactosidase genetically deficient in the disorder. This finding differs from that reported for fibroblasts from patients with metachromatic leukodystrophy, which showed abnormal accumulation and retention of sulfatide added to the culture media. However, degradation of added galactosylceramide to [3H]galactose by the GLD fibroblasts was only 25% of the control cells, while lactosylceramide was degraded at 70% of the normal rate. These findings are consistent with the known substrate specificities of the two acidic beta-galactosidases in human tissues; galactosylceramide is hydrolyzed almost exclusively by galactosylceramidase, while lactosylceramide can be hydrolyzed by both galactosylceramidase and GM1-ganglioside beta-galactosidase.
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PMID:Globoid cell leukodystrophy (Krabbe's disease). Metabolic studies with cultured fibroblasts. 73 Dec 65

In view of recent conflicting reports from two laboratories, activities of lactosylceramide beta-galactosidase were reinvestigated in detail in brains and livers of normal individuals and of patients with globoid cell leukodystrophy or GM1-gangliosidosis. Both sets of the apparently totally contradictory results were readily reproduced simply by using the different assay systems of the respective laboratories. With our own assay system, hepatic lactosylceramide beta-galactosidase appeared deficient only in Gm1-gangliosidosis, while it appeared deficient only in globoid cell leukodystrophy when the assay system of Wenger et al. (Wenger, D.A., Sattler, M., Clark, D., and McKelvey, H. (1974) Clin. Chim. Acta 56, 199-206) was used. Analyses of individual constitutents in the two assay systems revealed their complex effects on measured activities of the enzyme. The findings were strongly indicative of the existence of two genetically distinct lactosylceramide-cleaving enzymes. One enzyme (lactosylceramidase I) may be identical with galactosylceramide betal-galactosidase, and the other (lactosylceramidase II) is closely related to nonspecific 4-methylumbelliferyl beta-galactosidase. Normal human brain contains mostly lactosylceramidase I, while normal liver contains predominantly lactosylceramidase II. Lactosylceramidase I is genetically lacking globoid cell leukodystrophy, and lactosylceramidase II in GM1-gangliosidosis. Lactosylceramidase I is activated by either pure or crude taurocholate and by oleic acid and is only slightly activated by chloride ions. Lactosylceramidase II is activated by crude taurocholate but not by pure taurocholate. As activators, oleic acid is less effective and chloride more effective than for lactosylceramidase I. Citrate-phosphate buffer is more favorable to lactosylceramidase I than citrate buffer, while lactosylceramidase II responds in reverse. The standard assay system used by Wenger et al. determines almost exclusively lactosylceramidase I, while our own standard system is optimal for lactosylceramidase II and is less favorable for lactosylceramidase I. With a highly purified human hepatic beta-galactosidase preparation, exxentially free of galactosylceramide beta-galactosidase activity, lactosylceramide-cleaving activity determined by the Wenger system was less than 2 per cent of that determined by our system. If lactosylceramide beta-balactosidase assays are to be used for diagnosis of globoid cell leukodystrophy, it is absolutely essential to use an appropriate assay system in order to avoid errors of serious consequences.
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PMID:Lactosylceramide beta-galactosidase in human sphingolipidoses. Evidence for two genetically distinct enzymes. 80 71

The effect of bile salts on the hydrolysis of lactosylcermide by human beta-galactosidases in vitro was studied using cultured skin fibroblasts, liver and brain tissue. The evidence for two distinct enzymes that can catalyze the hydrolysis of lactosylceramide was observed when the bile salt was changed from pure sodium taurocholate to either crude taurocholate, or pure glycodeoxycholate, taurodeoxycholate or taurochenodeoxycholate. Tissues from patients with Krabbe's disease were found to be deficient in lactosylceramide beta-galactosidase activity (lactosylceramidase I) when pure taurocholate was used in the assay. When crude taurocholate was used in the assay, the Krabbe patients appeared to have normal activity for this enzyme. In place of crude taurocholate the pure salts of glycodeoxycholate, taurodeoxycholate and taurochenodeoxycholate worked even better to stimulate the second lactosylceramide beta-galactosidase activity and GM1 gangliosidosis patients exhibiting little if any activity. Therefore, lactosylcermidase I is stimulated by crude taurocholate or pure glycodeoxycholate, taurodeoxycholate and taurochenodeoxycholate. The use of pure bile salts to assay lactosylceramidase I and II will result in better reproducibility for these enzyme activities between laboratories.
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PMID:Effect of bile salts on lactosylceramide beta-galactosidase activities in human brain, liver and cultured skin fibroblasts. 81 51

Galactosylceramide beta-galactosidase (cerebrosidase) and nonspecific beta-galactosidase activities were measured in both cultured skin fibroblasts and leucocytes from a family with Krabbe's globoid cell leucodystrophy (GLD). The activities of these enzymes were also determined in cultured skin fibroblasts of a patient with GM1 gangliosidosis and in cultured amniotic fluid cells. While cerebrosidase activity was deficient in GLD fibroblasts and leucocytes, its activity in GM1 gangliosidosis fibroblasts was increased. Two forms of each enzyme were found on isoelectric focusing, but in the GM1 gangliosidosis fibroblasts, cerebrosidase activity occurred as a single but intermediate peak. The use of cultured cells in assessing isoenzyme abnormalities associated with certain neurolipidoses is discussed.
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PMID:Krabbe's globoid cell leucodystrophy. Studies on galactosylceramide beta-galactosidase and non-specific beta-galactosidase of leucocytes, cultured skin fibroblasts, and amniotic fluid cells. 81 52

Krabbe's infantile cerebral sclerosis with a prolonged course was present in a boy who became increasingly hypertonic during infancy and had an increased protein level in the spinal fluid. At 4 years he showed significant growth failure, profound mental retardation, spastic quadriplegia, bilateral optic atrophy, and depressed tendon reflexes. Conduction velocity in motor fibers of the median nerve had become progressively impaired. Autopsy at 5 years 10 months showed severe leukodystrophy with demyelination and gliosis. No stored breakdown products or globoid cells were seen in the brain. Galactosyl ceramide beta-galactosidase was virtually absent, and hardly any myelin was demonstrable on chemical and electron microscopic studies. The presence of globoid cells may not be essential for the pathologic diagnosis of Krabbe's leukodystrophy in the presence of appropriate enzyme deficiency.
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PMID:Krabbe's leukodystrophy without globoid cells. 98 9

Galactosylceramide beta-galactosidase and lactosylceramide beta-galactosidase activities were investigated in normal human brain, leu-kocytes and amniotic fluid cells. The enzymatic assays were performed on brains from 11 patients with Krabbe's disease, on leukocytes from 16 patients and 18 obligate heterozygotes, and on amniotic fluid cells from 9 foetuses at risk. The brain enzyme was solubilized from a 900 g-100000 g pellet. With this enzyme preparation a profound deficiency of galactosylceramide beta-galactosidase activity in brain, approximately 1% of that in age-matched controls was shown. The lactosylceramide beta-galactosidase activity of brain was also strongly reduced, but not to the same extent as the other beta-galactosidase. Galactosylceramide beta-galactosidase activity in leukocytes from patients with Krabbe's disease was generally less than 5% of that in age-matched controls and there was no overlap between the patients and the obligate heterozygotes. Carrier detection by the leukocyte enzyme was, however, not possible because of considerable overlap between heterozygotes and normal controls. The lactosylceramide beta-galactosidase activity was only moderately reduced in leukocytes, but strongly reduced in cerebral tissue from patients with Krabbe's disease. The changes in the glycolipid pattern of cerebral tissue, recently described by us in patients with Krabbe's disease, offers an explanation to the serious glycolipid beta-galactosidase deficiency in CNS.
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PMID:Chemical pathology of krabbe's disease. IV. Studies of galactosylceramide and lactosylceramide BETA-galactosidases in brain, white blood cells and aminotic fluid cells. 115 85

Prenatal diagnosis of globoid cell leukodystrophy using amniocentesis and enzyme studies of amniotic fluid cells is described. The 23-year-old patient had previously borne a child with the disorder. Amniocentesis was performed in the 17th week of pregnancy. Normal activity of cerebroside-beta-galactosidase was found in the amniotic fluid, but a 25% defect of the enzyme was found in 2 cultures of amniotic fluid cells. Diagnosis was confirmed by autopsy after the abortion of the fetus, by enzymatic tests and observation of globoid cells in the spinal cord. Enzymatic examination of amniotic fluid cells is recommended for the prenatal diagnosis of Krabbe's disease; enzyme levels in the amniotic fluid have no diagnostic value.
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PMID:[Prenatal diagnosis of globoid-cell leukodystrophy (Krabbe's disease) (author's transl)]. 126 11

A series of 6- and 8-acylamino-4-methylumbelliferyl beta-D-galactopyranosides, beta-D-glucopyranosides, and alpha-L-fucopyranosides having various fatty acid residues were synthesized; 6-(9) and 8-hexadecanoylamino-4-methylumbelliferyl beta-D-galactopyranoside (10) were shown to be substrates for human galactocerebrosidase. Analogs of 9 with shorter acyl residues (octanoyl and butanoyl) were substrates for another type of beta-D-galactosidase, i.e., GM1-ganglioside-beta-D-galactosidase. The specificity of various beta-D-galactosidases for synthetic D-galactopyranosides, differing in the length and position of their acylamide residue, tested with enzyme preparations from patients with two types of glycolipidosis, Krabbe's disease (galactocerebrosidase deficiency) and GM1-beta-galactosidase deficiency), suggested that 9 is a specific substrate for galactocerebrosidase in biochemical tests for Krabbe's disease. Fluorogenic 6-octanoyl- and 6-hexadecanoyl-amino-4-methylumbelliferyl beta-D-glucopyranoside were much less readily hydrolyzed by both human and animal glucocerebrosidase than chromogenic 2-hexadecanoylamino-4-nitrophenyl beta-D-glucopyranoside. Comparison of the hydrolysis of 4-methylumbelliferyl alpha-L-fucopyranoside with that of 6-hexadecanoylamino-4-methylumbelliferyl alpha-L-fucopyranoside by multiple forms of human alpha-L-fucosidase showed that the enzyme is capable of hydrolyzing not only hydrophilic but also synthetic, lipid-like substrates.
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PMID:The use of glycosides of 6- and 8-acylamino-4-methylumbelliferone in studies of the specificity and properties of human lysosomal glycolipid hydrolases. 159 66


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