Alpha-galactosidase

Galactosidase, alpha
PDB rendering based on 1r46.
Available structures PDB 1R46, 1R47, 3GXN, 3GXP, 3GXT, 3HG2, 3HG3, 3HG4, 3HG5, 3LX9, 3LXA, 3LXB, 3LXC
Identifiers
Symbols	GLA; GALA
External IDs	OMIM: 300644 MGI: 1347344 HomoloGene: 90852 GeneCards: GLA Gene
EC number	3.2.1.22
Gene Ontology Molecular function • catalytic activity • hydrolase activity, hydrolyzing O-glycosyl compounds • alpha-galactosidase activity • alpha-galactosidase activity • receptor binding • protein binding • hydrolase activity • protein homodimerization activity • cation binding • raffinose alpha-galactosidase activity Cellular component • extracellular region • extracellular region • cytoplasm • lysosome • lysosome • Golgi apparatus Biological process • oligosaccharide metabolic process • glycoside catabolic process • negative regulation of nitric oxide biosynthetic process • glycosylceramide catabolic process • glycosylceramide catabolic process • glycosphingolipid catabolic process • negative regulation of nitric-oxide synthase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2717	11605
Ensembl	ENSG00000102393	ENSMUSG00000031266
UniProt	P06280	Q3TLY5
RefSeq (mRNA)	NM_000169.2	NM_013463.2
RefSeq (protein)	NP_000160.1	NP_038491.2
Location (UCSC)	Chr X: 100.65 – 100.66 Mb	Chr X: 131.12 – 131.14 Mb
PubMed search	[1]	[2]

alpha-galactosidase
Identifiers
EC number	3.2.1.22
CAS number	9025-35-8
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles

Alpha-galactosidase is a glycoside hydrolase enzyme that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. It is encoded by the GLA gene.

Function

This enzyme is a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. It predominantly hydrolyzes ceramide trihexoside, and it can catalyze the hydrolysis of melibiose into galactose and glucose.

Pathology

A variety of mutations in this gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry's disease, a rare lysosomal storage disorder and sphingolipidosis that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties.

Two enzyme replacement therapies are available to functionally compensate for alpha-galactosidase deficiency. Agalsidase alpha and beta are both recombinant forms of the human α-galactosidase A enzyme and both have the same amino acid sequence as the native enzyme. Agalsidase alpha and beta differ in the structures of their oligosaccharide side chains.

Agalsidase alpha

The pharmaceutical company Shire manufactures agalsidase alpha under the brand name Replagal as a treatment for Fabry's disease., and was granted marketing approval in the EU in 2001. As of 2010, FDA approval is still pending before the drug can be marketed in the United States.

Agalsidase beta

The pharmaceutical company Genzyme produces synthetic agalsidase beta under the brand name Fabrazyme for treatment of Fabry's disease. In 2009, contamination at Genzyme's Allston, Massachusetts plant caused a worldwide shortage of Fabrazyme, and supplies were rationed to patients at one-third the recommended dose. Some patients have petitioned to break the company's patent on the drug under the "march-in" provisions of the Bayh–Dole Act.

See also

• Beano (dietary supplement)
• Beta-galactosidase
• Classification of α-galactosidases (according to CAZy)

Further reading

• Naumoff DG (2004). "Phylogenetic analysis of α-galactosidases of the GH27 family". Molecular Biology (Engl Transl) 38 (3): 388–399. PMID 15285616.  PDF
• Eng CM, Desnick RJ (1994). "Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene.". Hum. Mutat. 3 (2): 103–11. doi:10.1002/humu.1380030204. PMID 7911050. 
• Caillaud C, Poenaru L (2002). "[Gaucher's and Fabry's diseases: biochemical and genetic aspects]". J. Soc. Biol. 196 (2): 135–40. PMID 12360742. 
• Germain DP (2002). "[Fabry's disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects]". J. Soc. Biol. 196 (2): 161–73. PMID 12360745. 
• Schaefer E, Mehta A, Gal A (2005). "Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey.". Acta paediatrica (Oslo, Norway : 1992). Supplement 94 (447): 87–92; discussion 79. doi:10.1080/08035320510031045. PMID 15895718. 
• Levin M (2006). "Fabry disease.". Drugs Today 42 (1): 65–70. doi:10.1358/dot.2006.42.1.957357. PMID 16511611. 
• Lidove O, Joly D, Barbey F, et al. (2007). "Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature.". Int. J. Clin. Pract. 61 (2): 293–302. doi:10.1111/j.1742-1241.2006.01237.x. PMID 17263716. 
• Dean KJ, Sweeley CC (1979). "Studies on human liver alpha-galactosidases. I. Purification of alpha-galactosidase A and its enzymatic properties with glycolipid and oligosaccharide substrates.". J. Biol. Chem. 254 (20): 9994–10000. PMID 39940. 
• Ishii S, Sakuraba H, Suzuki Y (1992). "Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease.". Hum. Genet. 89 (1): 29–32. doi:10.1007/BF00207037. PMID 1315715. 
• Ioannou YA, Bishop DF, Desnick RJ (1992). "Overexpression of human alpha-galactosidase A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion.". J. Cell Biol. 119 (5): 1137–50. doi:10.1083/jcb.119.5.1137. PMC 2289730. PMID 1332979. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2289730. 
• von Scheidt W, Eng CM, Fitzmaurice TF, et al. (1991). "An atypical variant of Fabry's disease with manifestations confined to the myocardium.". N. Engl. J. Med. 324 (6): 395–9. doi:10.1056/NEJM199102073240607. PMID 1846223. 
• Koide T, Ishiura M, Iwai K, et al. (1990). "A case of Fabry's disease in a patient with no alpha-galactosidase A activity caused by a single amino acid substitution of Pro-40 by Ser.". FEBS Lett. 259 (2): 353–6. doi:10.1016/0014-5793(90)80046-L. PMID 2152885. 
• Kornreich R, Bishop DF, Desnick RJ (1990). "Alpha-galactosidase A gene rearrangements causing Fabry disease. Identification of short direct repeats at breakpoints in an Alu-rich gene.". J. Biol. Chem. 265 (16): 9319–26. PMID 2160973. 
• Sakuraba H, Oshima A, Fukuhara Y, et al. (1990). "Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease.". Am. J. Hum. Genet. 47 (5): 784–9. PMC 1683686. PMID 2171331. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683686. 
• Bernstein HS, Bishop DF, Astrin KH, et al. (1989). "Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene.". J. Clin. Invest. 83 (4): 1390–9. doi:10.1172/JCI114027. PMC 303833. PMID 2539398. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=303833. 
• Kornreich R, Desnick RJ, Bishop DF (1989). "Nucleotide sequence of the human alpha-galactosidase A gene.". Nucleic Acids Res. 17 (8): 3301–2. doi:10.1093/nar/17.8.3301. PMC 317741. PMID 2542896. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317741. 
• Bishop DF, Kornreich R, Desnick RJ (1988). "Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region.". Proc. Natl. Acad. Sci. U.S.A. 85 (11): 3903–7. doi:10.1073/pnas.85.11.3903. PMC 280328. PMID 2836863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=280328. 
• Quinn M, Hantzopoulos P, Fidanza V, Calhoun DH (1988). "A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A.". Gene 58 (2-3): 177–88. doi:10.1016/0378-1119(87)90374-X. PMID 2892762. 
• Bishop DF, Calhoun DH, Bernstein HS, et al. (1986). "Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme.". Proc. Natl. Acad. Sci. U.S.A. 83 (13): 4859–63. doi:10.1073/pnas.83.13.4859. PMC 323842. PMID 3014515. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=323842. 
• Lemansky P, Bishop DF, Desnick RJ, et al. (1987). "Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease.". J. Biol. Chem. 262 (5): 2062–5. PMID 3029062. 
• Tsuji S, Martin BM, Kaslow DC, et al. (1987). "Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A.". Eur. J. Biochem. 165 (2): 275–80. doi:10.1111/j.1432-1033.1987.tb11438.x. PMID 3036505. 

External links

• MeSH alpha-Galactosidase

This article incorporates text from the United States National Library of Medicine, which is in the public domain.