Galactosylceramidase
From Proteopedia
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<StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''> | <StructureSection load='3zr5' size='340' side='right' caption='Galactosylceramidase scene=''> | ||
| - | Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from | + | Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase <ref>RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb</ref> that removes galactose from galactosylceramide and other sphingolipids<ref name=Zizioli>PMID: 24463171</ref>. Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy<ref name=Deane>PMID: 21876145</ref>. |
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== Disease == | == Disease == | ||
| - | Defects in this enzyme cause | + | Defects in this enzyme cause a lysosomal storage disorder known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC<ref name=Deane>PMID: 21876145</ref>. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes<ref name=Belleri>PMID: 23983033</ref><ref name=Kohlschutter>PMID: 23622382</ref>. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated<ref name=Kohlschutter>PMID: 23622382</ref>. A common authentic model for this disease is the twitcher mouse model<ref name=Belleri>PMID: 23983033</ref>. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched<ref name=Kohlschutter>PMID: 23622382 </ref>. |
== Relevance == | == Relevance == | ||
Revision as of 20:02, 3 June 2014
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References
- ↑ RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. (n.d.). RCSB Protein Data Bank - RCSB PDB - 3ZR5 Structure Summary. Retrieved June 3, 2014, from www.rcsb.org DOI:10.2210/pdb3zr5/pdb
- ↑ Zizioli D, Guarienti M, Tobia C, Gariano G, Borsani G, Bresciani R, Ronca R, Giacopuzzi E, Preti A, Gaudenzi G, Belleri M, Di Salle E, Fabrias G, Casas J, Ribatti D, Monti E, Presta M. Molecular cloning and knockdown of galactocerebrosidase in zebrafish: new insights into the pathogenesis of Krabbe's disease. Biochim Biophys Acta. 2014 Apr;1842(4):665-75. doi: 10.1016/j.bbadis.2014.01.008., Epub 2014 Jan 24. PMID:24463171 doi:http://dx.doi.org/10.1016/j.bbadis.2014.01.008
- ↑ 3.0 3.1 Deane JE, Graham SC, Kim NN, Stein PE, McNair R, Cachon-Gonzalez MB, Cox TM, Read RJ. Insights into Krabbe disease from structures of galactocerebrosidase. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15169-73. Epub 2011 Aug 29. PMID:21876145 doi:10.1073/pnas.1105639108
- ↑ 4.0 4.1 Belleri M, Ronca R, Coltrini D, Nico B, Ribatti D, Poliani PL, Giacomini A, Alessi P, Marchesini S, Santos MB, Bongarzone ER, Presta M. Inhibition of angiogenesis by beta-galactosylceramidase deficiency in globoid cell leukodystrophy. Brain. 2013 Sep;136(Pt 9):2859-75. doi: 10.1093/brain/awt215. PMID:23983033 doi:http://dx.doi.org/10.1093/brain/awt215
- ↑ 5.0 5.1 5.2 Kohlschutter A. Lysosomal leukodystrophies: Krabbe disease and metachromatic leukodystrophy. Handb Clin Neurol. 2013;113:1611-8. doi: 10.1016/B978-0-444-59565-2.00029-0. PMID:23622382 doi:http://dx.doi.org/10.1016/B978-0-444-59565-2.00029-0
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