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4-methylumbelliferyl beta-galactoside + H2O
methylumbelliferone + beta-D-galactose
4-methylumbelliferyl-beta-D-galactopyranoside + H2O
4-methylumbelliferone + beta-D-galactopyranose
5-bromo-3-chloro-beta-galactopyranoside + H2O
?
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside + H2O
6-hexadecanoylamino-4-methylumbelliferone + beta-D-galactopyranose
D-galactosyl-alkyl-acyl-glycerol + H2O
?
-
a precursor of the seminolipid
-
-
?
D-galactosyl-N-acylsphingosine + H2O
?
D-galactosyl-N-acylsphingosine + H2O
D-galactose + N-acylsphingosine
D-galactosylceramide + H2O
D-galactose + ceramide
-
-
-
-
?
D-galactosylsphingoside + H2O
D-galactose + sphingosine
-
i.e. psychosine
-
-
?
galactocerebroside + H2O
D-galactose + N-acylceramide
galactosylceramide + H2O
D-galactose + N-acylceramide
GM1 ganglioside + H2O
D-galactose + N-acylceramide
lactosylsphingosine + H2O
lactose + sphingosine
N-stearoyl psychosine + H2O
D-galactose + N-stearoylsphingosine
-
-
-
-
?
psychosine + H2O
D-galactose + sphingosine
additional information
?
-
-
the enzyme is required for normal sperm maturation and function, enzyme deficiency leads to degeneration of oligodendrocytes, severe demyelination, and causes sperm abnormalities in the mouse model of human globoid cell leukodystrophy or Krabbe disease, mutant twitcher mice show reduced size of testis and sperm acrosomal membrane which is redundant, detached from the nucleus and folded over
-
-
?
4-methylumbelliferyl beta-galactoside + H2O
methylumbelliferone + beta-D-galactose
-
-
-
-
?
4-methylumbelliferyl beta-galactoside + H2O
methylumbelliferone + beta-D-galactose
-
-
-
-
?
4-methylumbelliferyl-beta-D-galactopyranoside + H2O
4-methylumbelliferone + beta-D-galactopyranose
-
pH 4.0, 30 min, 37°C
-
-
?
4-methylumbelliferyl-beta-D-galactopyranoside + H2O
4-methylumbelliferone + beta-D-galactopyranose
-
pH 4.0, 30 min, 37°C
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside + H2O
6-hexadecanoylamino-4-methylumbelliferone + beta-D-galactopyranose
-
-
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside + H2O
6-hexadecanoylamino-4-methylumbelliferone + beta-D-galactopyranose
-
fluorogenic substrate
-
-
?
6-hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside + H2O
6-hexadecanoylamino-4-methylumbelliferone + beta-D-galactopyranose
-
fluorogenic substrate
-
-
?
D-galactosyl-N-acylsphingosine + H2O
?
-
-
171506, 171507, 171508, 171509, 171510, 171511, 171512, 171514, 171515, 171516, 171517, 171518, 171519, 171522 -
-
?
D-galactosyl-N-acylsphingosine + H2O
?
-
-
-
?
D-galactosyl-N-acylsphingosine + H2O
?
-
-
-
-
?
D-galactosyl-N-acylsphingosine + H2O
?
-
-
-
-
?
D-galactosyl-N-acylsphingosine + H2O
D-galactose + N-acylsphingosine
-
-
171506, 171507, 171508, 171509, 171510, 171511, 171512, 171514, 171515, 171516, 171517, 171518, 171519, 171522 -
-
?
D-galactosyl-N-acylsphingosine + H2O
D-galactose + N-acylsphingosine
-
-
-
?
D-galactosyl-N-acylsphingosine + H2O
D-galactose + N-acylsphingosine
-
-
-
-
?
D-galactosyl-N-acylsphingosine + H2O
D-galactose + N-acylsphingosine
-
-
-
-
?
galactocerebroside + H2O
D-galactose + N-acylceramide
-
-
171506, 171507, 171508, 171509, 171510, 171511, 171512, 171514, 171515, 171516, 171517, 171518, 171519, 171522 -
-
?
galactocerebroside + H2O
D-galactose + N-acylceramide
-
-
-
?
galactocerebroside + H2O
D-galactose + N-acylceramide
-
-
-
-
?
galactocerebroside + H2O
D-galactose + N-acylceramide
-
-
-
-
?
galactosylceramide + H2O
D-galactose + N-acylceramide
-
-
-
-
?
galactosylceramide + H2O
D-galactose + N-acylceramide
-
-
-
?
galactosylceramide + H2O
D-galactose + N-acylceramide
-
-
-
-
?
GM1 ganglioside + H2O
D-galactose + N-acylceramide
-
-
-
-
?
GM1 ganglioside + H2O
D-galactose + N-acylceramide
-
-
-
-
?
lactosylsphingosine + H2O
lactose + sphingosine
-
-
-
-
?
lactosylsphingosine + H2O
lactose + sphingosine
-
-
-
-
?
psychosine + H2O
D-galactose + sphingosine
-
-
-
-
?
psychosine + H2O
D-galactose + sphingosine
-
galactosylsphingosine
-
-
?
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diagnostics
an assay is developed that can measure small amounts of residual galactosylcerebrosidase activity in leukocytes with high accuracy and can contribute, along with genotyping, biomarker analysis, and neurological imaging, a better plan for post-newborn screening follow-up for Krabbe disease
drug development
enhancers of beta-galactocerebrosidase are identified as potential small molecules therapies for Krabbe's disease
medicine
-
twitcher mouse, a model for globoid cell leucodystrophy
medicine
-
enzymatic diagnosis
medicine
-
enzymatic diagnosis
medicine
-
enzyme deficiency in globoid cell leucodystrophy or Krabbe disease
medicine
enzyme deficiency in globoid cell leucodystrophy or Krabbe disease
medicine
-
economical and fast histochemical way to distinguish neural cells expressing galactocerebrosidase from thoses that are deficient. This method enables the assessment of enzyme activity in virally-transduced cells as well as the biodistribution of galactocerebrosidase activity in Twitcher mice under gene or cell therapy
medicine
-
electrospray mass spectrometry combined with the use of biotinylated substrate conjugates and bioaffinity purification represents a new approach for the diagnosis of lysosomal storage disease, Krabbe disease
medicine
-
findings could lead to an improved therapy for globoid cell leukodystrophy, GLD, or Krabbe disease
medicine
-
globoid cell leukodystrophy, GLD or Krabbe disease, is caused by loss-of-fuction mutations in the GALC gene, injection of GALC improves the survival of the mouse model of GLD
medicine
-
diagnosis of Krabbe disease
medicine
-
diagnosis of Krabbe disease
medicine
-
lysosomal galactocerebrosidase GALC, which is defective in globoid cell leukodystrophy, is involved in the maintenance of a functional hematopoietic stem/progenitor cell niche by contributing to the control of the intracellular content of key sphingolipids. Both insufficient and supraphysiologic GALC activity by inherited genetic deficiency or forced gene expression in patients' cells and in the disease model induce alterations of the intracellular content of the bioactive GALC downstream products ceramide and sphingosine, and thus affect hematopoietic stem/progenitor cell survival and function and the functionality of the stem cell niche
medicine
mutations involved in Krabbe's disease are widely distributed throughout the protein. Mutations that are likely to result in severe misfolding include E114K and S257F in the TIM barrel, L364R and W410G in the beta-sandwich domain, and G537R and L629R in the lectin domain. Mutation E215K is exposed on the surface of the TIM barrel. The mutation confers an opposite charge on the same face as the substrate-binding pocket suggesting that the mechanism of disease for this mutation will involve the perturbation of a binding face for an activating factor. Residue P302 that is found on the surface of GALC very close to the substrate-binding pocket is mutated to arginine in Krabbe's disease. The beta-sandwich domain of a long loop forms an integral part of the substrate-binding site. R380 at the tip of this loop directly binds the galactose molecule in the active site, its mutation to tryptophan or leucine leads to severe infantile Krabbe's disease
medicine
enhancers of beta-galactocerebrosidase are identified as potential small molecules therapies for Krabbe Disease
medicine
incubation of human fibroblasts from patients bearing nonsense mutations with PTC124 (premature termination codon, a well-characterized compound known to induce ribosomal read-through) and NMDI1 (nonsense-mediated mRNA decay inhibitor 1) increases the levels of mRNA and rescues galactocerebrosidase enzymatic activity in a dose-dependent manner. The low but sustained expression of beta-galactocerebrosidase in oligodendrocytes is sufficient to improve the morphology of the differentiated cells. The in vitro approach provides the basis for further investigation of ribosomal read-through as an alternative therapeutic strategy to ameliorate the quality of life in selected Krabbe's disease patients
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Goda, S.; Kobayashi, T.; Goto, I.
Hydrolysis of galactosylsphingosine and lactosylsphingosine by beta-galactosidases in human brain and cultured fibroblasts
Biochim. Biophys. Acta
920
259-265
1987
Homo sapiens
brenda
Kobayashi, T.; Shinnoh, N.; Kuroiwa, Y.
Metabolism of galactosylceramide in the twitcher mouse, an animal model of human globoid cell leukodystrophy
Biochim. Biophys. Acta
879
215-220
1986
Homo sapiens, Mus musculus
brenda
Kobayashi, T.; Shinnoh, N.; Goto, I.; Kuroiwa, Y.
Hydrolysis of galactosylceramide is catalyzed by two genetically distinct acid beta-galactosidases
J. Biol. Chem.
260
14982-14987
1985
Homo sapiens
brenda
Kato, T.; Suzuki, Y.
Enzymatic determination of galactosylceramide galactosidase in tissues by NAD cycling
Anal. Biochem.
126
44-51
1982
Homo sapiens, Rattus norvegicus
brenda
Ben-Yoseph, Y.; Hungerford, M.; Nadler, H.L.
The interrelations between high- and low-molecular weight forms of normal and mutant (Krabbe-disease) galactocerebrosidase
Biochem. J.
189
9-15
1980
Homo sapiens
brenda
Hanada, E.; Suzuki, K.
Activation of human brain galactosylceramidase by phosphatidylserine
Biochim. Biophys. Acta
575
410-420
1979
Homo sapiens
brenda
Ben-Yoseph, Y.; Hungerford, M.; Nadler, H.L.
Galactosylceramide beta-galactosidase in Krabbe disease: partial purification and characterization of the mutant enzyme
Arch. Biochem. Biophys.
196
93-101
1979
Homo sapiens
brenda
Arora, R.C.; Lin, Y.N.; Radin, N.S.
The inhibitor-sensitive sites of galactosyl ceramide galactosidase
Arch. Biochem. Biophys.
156
77-83
1973
Rattus norvegicus
brenda
Rushton, A.R.; Dawson, G.
Glycosphinoglipid beta-galactosidases of cultured mammalian cells. Characterization of the enzymes from mouse cell line lmtk and human Lesch-Nyhan fibroblasts
Biochim. Biophys. Acta
388
92-105
1975
Homo sapiens, Mus musculus
brenda
Besley, G.T.N.
Isoelectric focusing of galactosylceramide beta-galactosylceramide beta-galactosidase in cultured skin fibroblasts of patients with Krabbes globoid-cell leucodystrophy
Biochem. Soc. Trans.
3
241-244
1975
Homo sapiens
brenda
Chiao, Y.B.; Moffitt, K.; Smallwood, Y.; Glew, R.H.
Glyconamides as inhibitors of human beta-glucosidases and beta-galactosidases
Arch. Biochem. Biophys.
192
1-9
1979
Homo sapiens
brenda
Wiederschain, G.; Raghavan, S.; Kolodny, E.
Characterization of 6-hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside as fluorogenic substrate of galactocerebrosidase for the diagnosis of Krabbe disease
Clin. Chim. Acta
205
87-96
1992
Homo sapiens, Mus musculus
brenda
Chen, Y.Q.; Wenger, D.A.
Galactocerebrosidase from human urine: purification and partial characterization
Biochim. Biophys. Acta
1170
53-61
1993
Homo sapiens
brenda
Sakai, N.; Inui, K.; Midorikawa, M.; Okuno, Y.; Ueda, S.; Iwamatsu, A.; Okada, S.
Purification and characterization of galactocerebrosidase from human lymphocytes
J. Biochem.
116
615-620
1994
Homo sapiens
brenda
Sakai, N.; Inui, K.; Fujii, N.; Fukushima, H.; Nishimoto, J.; Yanagihara, I.; Isegawa, Y.; Iwamatsu, A.; Okada, S.
Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase
Biochem. Biophys. Res. Commun.
198
485-491
1994
Homo sapiens
brenda
Luzi, P.; Rafi, M.A.; Victoria, T.; Baskin, G.B.; Wenger, D.A.
Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate
Genomics
42
319-324
1997
Macaca mulatta (O02791), Macaca mulatta
brenda
Nagano, S.; Yamada, T.; Shinnoh, N.; Furuya, H.; Taniwaki, T.; Kira, J.
Expression and processing of recombinant human galactosylceramidase
Clin. Chim. Acta
276
53-61
1998
Homo sapiens
brenda
deGasperi, R.; Raghavan, S.S.; Sosa, M.G.; Kolodny, E.H.; Carrier, C.; Rubenstein, P.; Peters, C.; Wagner, J.; Kurtzberg, J.; Krivit, W.
Measurements from normal umbilical cord blood of four lysosomal enzymatic activities: alpha-L-iduronidase (Hurler), galactocerebrosidase (globoid cell leukodystrophy), arylsulfatase A (metachromatic leukodystrophy), arylsulfatase B (Maroteaux-Lamy)
Bone Marrow Transplant.
25
541-544
2000
Homo sapiens
brenda
Zhou, X.; Turecek, F.; Scott, C.R.; Gelb, M.H.
Quantification of cellular acid sphingomyelinase and galactocerebroside beta-galactosidase activities by electrospray ionization mass spectrometry
Clin. Chem.
47
874-881
2001
Homo sapiens
brenda
Dolcetta, D.; Perani, L.; Givogri, M.I.; Galbiati, F.; Orlacchio, A.; Martino, S.; Roncarolo, M.G.; Bongarzone, E.
Analysis of galactocerebrosidase activity in the mouse brain by a new histological staining method
J. Neurosci. Res.
77
462-464
2004
Mus musculus
brenda
Luddi, A.; Strazza, M.; Carbone, M.; Moretti, E.; Costantino-Ceccarini, E.
Galactosylceramidase deficiency causes sperm abnormalities in the mouse model of globoid cell leukodystrophy
Exp. Cell Res.
304
59-68
2005
Mus musculus
brenda
Lee, W.C.; Tsoi, Y.K.; Troendle, F.J.; DeLucia, M.W.; Ahmed, Z.; Dicky, C.A.; Dickson, D.W.; Eckman, C.B.
Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophy
FASEB J.
21
2520-2527
2007
Mus musculus
brenda
Zhang, X.Y.; Dinh, A.; Cronin, J.; Li, S.C.; Reiser, J.
Cellular uptake and lysosomal delivery of galactocerebrosidase tagged with the HIV Tat protein transduction domain
J. Neurochem.
104
1055-1064
2008
Mus musculus
brenda
Martino, S.; Tiribuzi, R.; Tortori, A.; Conti, D.; Visigalli, I.; Lattanzi, A.; Biffi, A.; Gritti, A.; Orlacchio, A.
Specific determination of beta-galactocerebrosidase activity via competitive inhibition of beta-galactosidase
Clin. Chem.
55
541-548
2009
Homo sapiens, Mus musculus
brenda
Visigalli, I.; Ungari, S.; Martino, S.; Park, H.; Cesani, M.; Gentner, B.; Sergi Sergi, L.; Orlacchio, A.; Naldini, L.; Biffi, A.
The galactocerebrosidase enzyme contributes to the maintenance of a functional hematopoietic stem cell niche
Blood
116
1857-1866
2010
Homo sapiens, Mus musculus
brenda
Deane, J.E.; Graham, S.C.; Kim, N.N.; Stein, P.E.; McNair, R.; Cachon-Gonzalez, M.B.; Cox, T.M.; Read, R.J.
Insights into Krabbe disease from structures of galactocerebrosidase
Proc. Natl. Acad. Sci. USA
108
15169-15173
2011
Mus musculus (P54818)
brenda
Liao, H.C.; Spacil, Z.; Ghomashchi, F.; Escolar, M.L.; Kurtzberg, J.; Orsini, J.J.; Turecek, F.; Scott, C.R.; Gelb, M.H.
Lymphocyte galactocerebrosidase activity by LC-MS/MS for post-newborn screening evaluation of Krabbe disease
Clin. Chem.
63
1363-1369
2017
Homo sapiens (P54803)
brenda
Scott-Hewitt, N.J.; Folts, C.J.; Hogestyn, J.M.; Piester, G.; Mayer-Proeschel, M.; Noble, M.D.
Heterozygote galactocerebrosidase (GALC) mutants have reduced remyelination and impaired myelin debris clearance following demyelinating injury
Hum. Mol. Genet.
26
2825-2837
2017
Mus musculus (P54818)
brenda
Saavedra-Matiz, C.A.; Luzi, P.; Nichols, M.; Orsini, J.J.; Caggana, M.; Wenger, D.A.
Expression of individual mutations and haplotypes in the galactocerebrosidase gene identified by the newborn screening program in New York State and in confirmed cases of Krabbes disease
J. Neurosci. Res.
94
1076-1083
2016
Homo sapiens (P54803), Homo sapiens
brenda
Jang, D.S.; Ye, W.; Guimei, T.; Solomon, M.; Southall, N.; Hu, X.; Marugan, J.; Ferrer, M.; Maegawa, G.H.
Cell-based high-throughput screening identifies galactocerebrosidase enhancers as potential small-molecule therapies for Krabbes disease
J. Neurosci. Res.
94
1231-1245
2016
Homo sapiens (P54803), Homo sapiens
brenda
Luddi, A.; Crifasi, L.; Capaldo, A.; Piomboni, P.; Costantino-Ceccarini, E.
Suppression of galactocerebrosidase premature termination codon and rescue of galactocerebrosidase activity in twitcher cells
J. Neurosci. Res.
94
1273-1283
2016
Homo sapiens (P54803), Homo sapiens, Mus musculus (P54818), Mus musculus
brenda