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

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

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

Progressive spasticity, blindness, loss of skills, and neuropathy developed in a 4.5-month-old boy. When examined at 13 months, galactocerebrosidase and galactosylceramide-beta-galactosidase activities were deficient in leukocytes. Intramuscular nerves and a sural nerve biopsy specimen showed loss of nerve fibers, interstitial fibrosis, and axonal degeneration, rather than the segmental demyelination that predominates in most cases. A muscle biopsy specimen showed congenital muscle fiber-type disproportion (CMFTD). This case confirms a previous report of CMFTD in Krabbe's disease and supports a neurogenic mechanism as the basis for CMFTD.
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PMID:Congenital muscle fiber-type disproportion in Krabbe's leukodystrophy. 727 38

Three to nine days after administration of suramin, 500 mg/kg intravenously in rats, a small amount of the drug (about 0.25 micromoles/g tissue) was retained by the liver and spleen, and a larger amount (about 1.2 micromoles/g tissue) was retained by the kidneys. The activities of the sphingolipid hydrolases beta-hexosaminidase and GM3-sialidase were strongly inhibited by suramin in vitro. The activity of beta-hexosaminidase was inhibited 70% by 10(-5M) and 85% by 10(-4M) suramin, and the activity of GM3-sialidase was inhibited 80% by 10(-4M) suramin. The activities of sphingomyelinase and beta-galactosidase were also inhibited by suramin but at higher concentrations of the drug. Suramin, in vitro is a weak inhibitor of glucocerebrosidase, galactocerebrosidase, alpha-galactosidase and arylsulfatase A (less than 50% inhibition at 10(-3M) concentration of the drug). The inhibition of beta-hexosaminidase by suramin was non-competitive. Inhibition of beta-hexosaminidase and GM3-sialidase may explain the accumulation of GM2 and GM3 gangliosides in the brains of rats treated intracerebrally with suramin (Constantopoulos et al, 1980).
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PMID:Effect of suramin on the activities of degradative enzymes of sphingolipids in rats. 729 29