Galactosylceramidase Explained

Galactosylceramidase
Ec Number:	3.2.1.46
Cas Number:	9027-89-8
Go Code:	0004336

Galactosylceramidase (or galactocerebrosidase),, is an enzyme that removes galactose from ceramide derivatives (galactosylceramides) by catalysing the hydrolysis of galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride.

It is a lysosomal protein, encoded in humans by the GALC gene.^{[1] [2]} Mutations in this gene have been associated with Krabbe disease, also known as galactosylceramide lipidosis.^[1]

References

Further reading

• Lee WC, Kang D, Causevic E, etal . Molecular characterization of mutations that cause globoid cell leukodystrophy and pharmacological rescue using small molecule chemical chaperones. . J. Neurosci. . 30 . 16 . 5489–5497 . 2010 . 20410102 . 10.1523/JNEUROSCI.6383-09.2010 . 3278277.
• Wenger DA, Rafi MA, Luzi P . Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. . Hum. Mutat. . 10 . 4 . 268–279 . 1997 . 9338580 . 10.1002/(SICI)1098-1004(1997)10:4<268::AID-HUMU2>3.0.CO;2-D . 36148722 . free .
• De Gasperi R, Gama Sosa MA, Sartorato EL, etal . Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy. . Am. J. Hum. Genet. . 59 . 6 . 1233–1242 . 1996 . 8940268 . 1914878.
• Tappino B, Biancheri R, Mort M, etal . Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease. . Hum. Mutat. . 31 . 12 . E1894–1914 . 2010 . 20886637 . 10.1002/humu.21367 . 3052420.
• Formichi P, Radi E, Battisti C, etal . Psychosine-induced apoptosis and cytokine activation in immune peripheral cells of Krabbe patients. . J. Cell. Physiol. . 212 . 3 . 737–743 . 2007 . 17458901 . 10.1002/jcp.21070 . 39182882 .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129.
• Franke A, McGovern DP, Barrett JC, etal . Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. . Nat. Genet. . 42 . 12 . 1118–1125 . 2010 . 21102463 . 10.1038/ng.717 . 3299551.
• Wenger DA, Rafi MA, Luzi P, etal . Krabbe disease: genetic aspects and progress toward therapy. . Mol. Genet. Metab. . 70 . 1 . 1–9 . 2000 . 10833326 . 10.1006/mgme.2000.2990 .
• Lissens W, Arena A, Seneca S, etal . A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region. . Hum. Mutat. . 28 . 7 . 742 . 2007 . 17579360 . 10.1002/humu.9500 . 1705020 . free .
• Beier UH . Görögh T . Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells. . Int. J. Cancer . 115 . 1 . 6–10 . 2005 . 15657896 . 10.1002/ijc.20851 . 1013550 .
• Xu C, Sakai N, Taniike M, etal . Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation. . J. Hum. Genet. . 51 . 6 . 548–554 . 2006 . 16607461 . 10.1007/s10038-006-0396-3 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–2127 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928.
• De Gasperi R, Gama Sosa MA, Sartorato E, etal . Molecular basis of late-life globoid cell leukodystrophy. . Hum. Mutat. . 14 . 3 . 256–262 . 1999 . 10477434 . 10.1002/(SICI)1098-1004(1999)14:3<256::AID-HUMU9>3.0.CO;2-6 . 27655 . free .
• Furuya H, Kukita Y, Nagano S, etal . Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients. . Hum. Genet. . 100 . 3–4 . 450–456 . 1997 . 9272171 . 10.1007/s004390050532. 22928816 .
• Fu L, Inui K, Nishigaki T, etal . Molecular heterogeneity of Krabbe disease. . J. Inherit. Metab. Dis. . 22 . 2 . 155–162 . 1999 . 10234611 . 10.1023/A:1005449919660. 24368901 .
• Sakai N, Fukushima H, Inui K, etal . Human galactocerebrosidase gene: promoter analysis of the 5'-flanking region and structural organization. . Biochim. Biophys. Acta . 1395 . 1 . 62–67 . 1998 . 9434153 . 10.1016/S0167-4781(97)00140-1.
• Harzer K, Knoblich R, Rolfs A, etal . Residual galactosylsphingosine (psychosine) beta-galactosidase activities and associated GALC mutations in late and very late onset Krabbe disease. . Clin. Chim. Acta . 317 . 1–2 . 77–84 . 2002 . 11814461 . 10.1016/S0009-8981(01)00791-4 .
• Flachsbart F, Franke A, Kleindorp R, etal . Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. . Mutat. Res. . 694 . 1–2 . 13–19 . 2010 . 20800603 . 10.1016/j.mrfmmm.2010.08.006 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . free .
• Hendrickson SL, Lautenberger JA, Chinn LW, etal . Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. . PLOS ONE . 5 . 9 . e12862 . 2010 . 20877624 . 10.1371/journal.pone.0012862 . 2943476. 2010PLoSO...512862H . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Krabbe disease
• OMIM entries on Krabbe disease
  • PDBe-KB provides an overview of all the structure information available in the PDB for Mlouse Galactocerebrosidase

Notes and References

1. Web site: Entrez Gene: galactosylceramidase.
2. Lee WC, Tsoi YK, Troendle FJ, etal . Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophy . FASEB J. . 21 . 10 . 2520–2527 . August 2007 . 17403939 . 10.1096/fj.06-6169com . free . 19511563 .