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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{enzyme
| Name = alpha-galactosidase
| EC_number = 3.2.1.22
| CAS_number = 9025-35-8
| IUBMB_EC_number = 3/2/1/22
| GO_code = 0004557
| image =
| width =
| caption =
}}
 
'''Alpha-galactosidase''' is a [[glycoside hydrolase]] [[enzyme]] that hydrolyses the terminal alpha-galactosyl [[moiety (chemistry)|moieties]] from glycolipids and glycoproteins.  It is encoded by the ''GLA'' gene.<ref name="pmid2997789">{{cite journal |vauthors=Calhoun DH, Bishop DF, Bernstein HS, Quinn M, Hantzopoulos P, Desnick RJ |title=Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=82 |issue=21 |pages=7364–8 |year=1985 |pmid=2997789 |pmc=391345 |doi=10.1073/pnas.82.21.7364 |bibcode=1985PNAS...82.7364C }}</ref> Two [[recombinant DNA|recombinant]] forms of alpha-galactosidase are called '''agalsidase alpha''' ([[International Nonproprietary Name|INN]]) and '''agalsidase beta''' (INN).
 
== 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 disease]], a rare [[lysosomal storage disorder]] and [[sphingolipidosis]] that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties.<ref>{{cite web | title = Entrez Gene: GLA galactosidase, alpha| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2717| accessdate = }}</ref>
 
Two [[enzyme replacement therapy|enzyme replacement therapies]] are available to functionally compensate for alpha-galactosidase deficiency. Agalsidase alpha and beta are both [[Recombinant DNA|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.<ref name="pmid19707461">{{cite journal | vauthors = Fervenza FC, Torra R, Warnock DG | title = Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease | journal = Biologics | volume = 2 | issue = 4 | pages = 823–43 |date=December 2008 | pmid = 19707461 | pmc = 2727881 | doi = 10.2147/btt.s3770| url = | issn = }}</ref>


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
=== Agalsidase alpha ===
{{GNF_Protein_box
| image = PBB_Protein_GLA_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1r46.
| Name = Galactosidase, alpha
| HGNCid = 4296
| Symbol = GLA
| AltSymbols =; GALA
| OMIM = 301500
| ECnumber = 
| Homologene = 55441
| MGIid = 1347344
| GeneAtlas_image1 = PBB_GE_GLA_214430_at_tn.jpg
| Function = {{GNF_GO|id=GO:0004553 |text = hydrolase activity, hydrolyzing O-glycosyl compounds}} {{GNF_GO|id=GO:0004557 |text = alpha-galactosidase activity}} {{GNF_GO|id=GO:0005102 |text = receptor binding}} {{GNF_GO|id=GO:0042803 |text = protein homodimerization activity}} {{GNF_GO|id=GO:0043169 |text = cation binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005764 |text = lysosome}} {{GNF_GO|id=GO:0005794 |text = Golgi apparatus}}
| Process = {{GNF_GO|id=GO:0008152 |text = metabolic process}} {{GNF_GO|id=GO:0009311 |text = oligosaccharide metabolic process}} {{GNF_GO|id=GO:0045019 |text = negative regulation of nitric oxide biosynthetic process}} {{GNF_GO|id=GO:0046479 |text = glycosphingolipid catabolic process}} {{GNF_GO|id=GO:0051001 |text = negative regulation of nitric-oxide synthase activity}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2717
    | Hs_Ensembl = ENSG00000102393
    | Hs_RefseqProtein = NP_000160
    | Hs_RefseqmRNA = NM_000169
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = X
    | Hs_GenLoc_start = 100539453
    | Hs_GenLoc_end = 100549607
    | Hs_Uniprot = P06280
    | Mm_EntrezGene = 11605
    | Mm_Ensembl = ENSMUSG00000031266
    | Mm_RefseqmRNA = NM_013463
    | Mm_RefseqProtein = NP_038491
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = X
    | Mm_GenLoc_start = 129934521
    | Mm_GenLoc_end = 129947287
    | Mm_Uniprot = Q3TLY5
  }}
}}
{{SI}}
{{CMG}}


The pharmaceutical company [[Shire plc|Shire]] manufactures agalsidase alfa (INN) under the [[trade name]] [[Replagal]] as a treatment for Fabry disease,<ref name="pmid22946754">{{cite journal | author = Keating GM | title = Agalsidase alfa: a review of its use in the management of Fabry disease | journal = BioDrugs | volume = 26 | issue = 5 | pages = 335–54 |date=October 2012 | pmid = 22946754 | doi = 10.2165/11209690-000000000-00000 }}</ref> and was granted marketing approval in the EU in 2001.<ref name="url_FierceBiotech">{{cite web | url = http://www.fiercebiotech.com/press-releases/shire-submits-biologics-license-application-bla-replagal-u-s-food-and-drug-administra | title = Shire Submits Biologics License Application (BLA) for REPLAGAL with the U.S. Food and Drug Administration (FDA)  | publisher = FierceBiotech }}</ref>  FDA approval was applied for the United States.<ref name="npr">{{cite web|url=http://www.npr.org/blogs/health/2010/08/04/128973687/with-a-life-saving-medicine-in-short-supply-patients-want-patent-broken|title=With A Life-Saving Medicine In Short Supply, Patients Want Patent Broken|accessdate=2010-09-02|date=2010-08-04| archiveurl= https://web.archive.org/web/20100914063356/http://www.npr.org/blogs/health/2010/08/04/128973687/with-a-life-saving-medicine-in-short-supply-patients-want-patent-broken | archivedate= 14 September 2010 <!--DASHBot-->| deadurl= no}}</ref>  However, in 2012, Shire withdrew their application for approval in the United States citing that the agency will require additional clinical trials before approval.<ref name="www.pharmatimes.com">{{cite web|url=http://www.pharmatimes.com/article/12-03-15/Shire_withdraws_Replagal_in_USA_as_FDA_wants_more_trials.aspx |title=Shire withdraws Replagal in USA as FDA wants more trials |author=Grogan K |work= |publisher=PharmaTimes |date=2012-03-15 |deadurl=yes |archiveurl=https://web.archive.org/web/20140819130944/http://www.pharmatimes.com/article/12-03-15/Shire_withdraws_Replagal_in_USA_as_FDA_wants_more_trials.aspx |archivedate=2014-08-19 }}</ref>


=== Agalsidase beta ===


==Overview==
The pharmaceutical company [[Genzyme]] produces synthetic agalsidase beta (INN) under the trade name Fabrazyme for treatment of Fabry 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]].<ref name="npr" />
'''Alpha-galactosidase''' is a [[glycoside hydrolase]] [[enzyme]] encoded by the {{gene|GLA}} gene.


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
=== Over-the-counter brand names ===
{{PBB_Summary
Alpha-galactosidase is an active ingredient in [[Beano (dietary supplement)|Beano]], CVS BeanAid, Enzymedica's BeanAssist. These products are marketed to reduce stomach gas production after eating foods known to cause gas. There are dozens of generic brands containing the enzyme in the United States. It is optimally active at 55 degrees C, after which its half-life is 120 minutes.<ref>{{cite journal |vauthors=Patil AG, K PK, Mulimani VH, Veeranagouda Y, Lee K |title=alpha-Galactosidase from Bacillus megaterium VHM1 and its application in removal of flatulence-causing factors from soymilk |journal=Journal of Microbiology and Biotechnology |volume=20 |issue=11 |pages=1546–54 |year=2010 |pmid=21124061 |doi=10.4014/jmb.0912.12012 }}</ref>
| section_title =
| summary_text = This gene encodes a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. This enzyme predominantly hydrolyzes ceramide trihexoside, and it can catalyze the hydrolysis of melibiose into galactose and glucose. A variety of mutations in this gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry disease, a rare lysosomal storage disorder that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties.<ref>{{cite web | title = Entrez Gene: GLA galactosidase, alpha| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2717| accessdate = }}</ref>
}}
==Pathology==
A deficiency is associated with [[Fabry's disease]].


==See also==
==See also==
* [[Beano (dietary supplement)]]
* [[Beta-galactosidase]]
* [[Beta-galactosidase]]
* [[Migalastat]], a drug targeting alpha-galactosidase
* [[:ru:Image:MEL.jpg|Classification of α-galactosidases (according to CAZy)]]


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal |vauthors=Naumov DG |title=[Phylogenetic analysis of alpha-galactosidases of the GH27 family] |language=Russian |journal=Molekuliarnaia Biologiia |volume=38 |issue=3 |pages=463–76 |year=2004 |pmid=15285616 }} Republished as: {{cite journal |last1=Naumoff |first1=D. G. |title=Phylogenetic Analysis of α-Galactosidases of the GH27 Family |journal=Molecular Biology |volume=38 |issue=3 |year=2004 |pages=388–400 |doi=10.1023/B:MBIL.0000032210.97006.de }}
| citations =
*{{cite journal |vauthors=Eng CM, Desnick RJ |title=Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene |journal=Human Mutation |volume=3 |issue=2 |pages=103–11 |year=1994 |pmid=7911050 |doi=10.1002/humu.1380030204 }}
*{{cite journal | author=Naumoff DG |title=Phylogenetic analysis of α-galactosidases of the GH27 family |journal=Molecular Biology (Engl Transl) |volume=38 |issue=3 |pages=388-399 |year=2004 |pmid=15285616 |doi=  }} [http://bioinform.genetika.ru/members/Naumoff/MB2004E.pdf PDF]
*{{cite journal |vauthors=Caillaud C, Poenaru L |title=Maladies de Gaucher et de Fabry: aspects biochimiques et génétiques |trans-title=Gaucher's and Fabry's diseases: biochemical and genetic aspects |language=French |journal=Journal De La SociéTé De Biologie |volume=196 |issue=2 |pages=135–40 |year=2002 |id={{INIST|13891620}} |pmid=12360742 }}
*{{cite journal | author=Eng CM, Desnick RJ |title=Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene. |journal=Hum. Mutat. |volume=3 |issue= 2 |pages= 103-11 |year= 1994 |pmid= 7911050 |doi= 10.1002/humu.1380030204 }}
*{{cite journal |vauthors=Germain DP |title=Maladie de Fabry (déficit en alpha-galactosidase A): Physiopathologie, signes cliniques et aspects génétiques |trans-title=Fabry's disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects |language=French |journal=Journal De La SociéTé De Biologie |volume=196 |issue=2 |pages=161–73 |year=2002 |id={{INIST|13891623}} |pmid=12360745 }}
*{{cite journal | author=Caillaud C, Poenaru L |title=[Gaucher's and Fabry's diseases: biochemical and genetic aspects] |journal=J. Soc. Biol. |volume=196 |issue= 2 |pages= 135-40 |year= 2002 |pmid= 12360742 |doi= }}
*{{cite journal |vauthors=Schaefer E, Mehta A, Gal A |title=Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey |journal=Acta Paediatrica |volume=94 |issue=447 |pages=87–92; discussion 79 |year=2005 |pmid=15895718 |doi=10.1080/08035320510031045 }}
*{{cite journal | author=Germain DP |title=[Fabry's disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects] |journal=J. Soc. Biol. |volume=196 |issue= 2 |pages= 161-73 |year= 2002 |pmid= 12360745 |doi=  }}
*{{cite journal |vauthors=Levin M |title=Fabry disease |journal=Drugs of Today |volume=42 |issue=1 |pages=65–70 |year=2006 |pmid=16511611 |doi=10.1358/dot.2006.42.1.957357 }}
*{{cite journal | author=Schaefer E, Mehta A, Gal A |title=Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey. |journal=Acta paediatrica (Oslo, Norway : 1992). Supplement |volume=94 |issue= 447 |pages= 87-92; discussion 79 |year= 2005 |pmid= 15895718 |doi= }}
*{{cite journal |vauthors=Lidove O, Joly D, Barbey F, Bekri S, Alexandra JF, Peigne V, Jaussaud R, Papo T |title=Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature |journal=International Journal of Clinical Practice |volume=61 |issue=2 |pages=293–302 |year=2007 |pmid=17263716 |doi=10.1111/j.1742-1241.2006.01237.x }}
*{{cite journal | author=Levin M |title=Fabry disease. |journal=Drugs Today |volume=42 |issue= 1 |pages= 65-70 |year= 2006 |pmid= 16511611 |doi= 10.1358/dot.2006.42.1.957357 }}
*{{cite journal |vauthors=Dean KJ, Sweeley CC |title=Studies on human liver alpha-galactosidases. I. Purification of alpha-galactosidase A and its enzymatic properties with glycolipid and oligosaccharide substrates |journal=The Journal of Biological Chemistry |volume=254 |issue=20 |pages=9994–10000 |year=1979 |pmid=39940 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=39940 }}
*{{cite journal | author=Lidove O, Joly D, Barbey F, ''et al.'' |title=Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature. |journal=Int. J. Clin. Pract. |volume=61 |issue= 2 |pages= 293-302 |year= 2007 |pmid= 17263716 |doi= 10.1111/j.1742-1241.2006.01237.x }}
*{{cite journal |vauthors=Ishii S, Sakuraba H, Suzuki Y |title=Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease |journal=Human Genetics |volume=89 |issue=1 |pages=29–32 |year=1992 |pmid=1315715 |doi=10.1007/BF00207037 }}
*{{cite journal | author=Dean KJ, Sweeley CC |title=Studies on human liver alpha-galactosidases. I. Purification of alpha-galactosidase A and its enzymatic properties with glycolipid and oligosaccharide substrates. |journal=J. Biol. Chem. |volume=254 |issue= 20 |pages= 9994-10000 |year= 1979 |pmid= 39940 |doi= }}
*{{cite journal |vauthors=Ioannou YA, Bishop DF, Desnick RJ |title=Overexpression of human alpha-galactosidase A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion |journal=The Journal of Cell Biology |volume=119 |issue=5 |pages=1137–50 |year=1992 |pmid=1332979 |pmc=2289730 |doi=10.1083/jcb.119.5.1137 }}
*{{cite journal | author=Ishii S, Sakuraba H, Suzuki Y |title=Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease. |journal=Hum. Genet. |volume=89 |issue= 1 |pages= 29-32 |year= 1992 |pmid= 1315715 |doi= }}
*{{cite journal |vauthors=von Scheidt W, Eng CM, Fitzmaurice TF, Erdmann E, Hübner G, Olsen EG, Christomanou H, Kandolf R, Bishop DF, Desnick RJ |title=An atypical variant of Fabry's disease with manifestations confined to the myocardium |journal=The New England Journal of Medicine |volume=324 |issue=6 |pages=395–9 |year=1991 |pmid=1846223 |doi=10.1056/NEJM199102073240607 }}
*{{cite journal | author=Ioannou YA, Bishop DF, Desnick RJ |title=Overexpression of human alpha-galactosidase A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion. |journal=J. Cell Biol. |volume=119 |issue= 5 |pages= 1137-50 |year= 1992 |pmid= 1332979 |doi= }}
*{{cite journal |vauthors=Koide T, Ishiura M, Iwai K, Inoue M, Kaneda Y, Okada Y, Uchida T |title=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 |journal=FEBS Letters |volume=259 |issue=2 |pages=353–6 |year=1990 |pmid=2152885 |doi=10.1016/0014-5793(90)80046-L }}
*{{cite journal | author=von Scheidt W, Eng CM, Fitzmaurice TF, ''et al.'' |title=An atypical variant of Fabry's disease with manifestations confined to the myocardium. |journal=N. Engl. J. Med. |volume=324 |issue= 6 |pages= 395-9 |year= 1991 |pmid= 1846223 |doi= }}
*{{cite journal |vauthors=Kornreich R, Bishop DF, Desnick RJ |title=Alpha-galactosidase A gene rearrangements causing Fabry disease. Identification of short direct repeats at breakpoints in an Alu-rich gene |journal=The Journal of Biological Chemistry |volume=265 |issue=16 |pages=9319–26 |year=1990 |pmid=2160973 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=2160973}}
*{{cite journal | author=Koide T, Ishiura M, Iwai K, ''et al.'' |title=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. |journal=FEBS Lett. |volume=259 |issue= 2 |pages= 353-6 |year= 1990 |pmid= 2152885 |doi= }}
*{{cite journal |vauthors=Sakuraba H, Oshima A, Fukuhara Y, Shimmoto M, Nagao Y, Bishop DF, Desnick RJ, Suzuki Y |title=Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease |journal=American Journal of Human Genetics |volume=47 |issue=5 |pages=784–9 |year=1990 |pmid=2171331 |pmc=1683686 }}
*{{cite journal | author=Kornreich R, Bishop DF, Desnick RJ |title=Alpha-galactosidase A gene rearrangements causing Fabry disease. Identification of short direct repeats at breakpoints in an Alu-rich gene. |journal=J. Biol. Chem. |volume=265 |issue= 16 |pages= 9319-26 |year= 1990 |pmid= 2160973 |doi= }}
*{{cite journal |vauthors=Bernstein HS, Bishop DF, Astrin KH, Kornreich R, Eng CM, Sakuraba H, Desnick RJ |title=Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene |journal=The Journal of Clinical Investigation |volume=83 |issue=4 |pages=1390–9 |year=1989 |pmid=2539398 |pmc=303833 |doi=10.1172/JCI114027 }}
*{{cite journal | author=Sakuraba H, Oshima A, Fukuhara Y, ''et al.'' |title=Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease. |journal=Am. J. Hum. Genet. |volume=47 |issue= 5 |pages= 784-9 |year= 1990 |pmid= 2171331 |doi= }}
*{{cite journal |vauthors=Kornreich R, Desnick RJ, Bishop DF |title=Nucleotide sequence of the human alpha-galactosidase A gene |journal=Nucleic Acids Research |volume=17 |issue=8 |pages=3301–2 |year=1989 |pmid=2542896 |pmc=317741 |doi=10.1093/nar/17.8.3301 }}
*{{cite journal | author=Bernstein HS, Bishop DF, Astrin KH, ''et al.'' |title=Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene. |journal=J. Clin. Invest. |volume=83 |issue= 4 |pages= 1390-9 |year= 1989 |pmid= 2539398 |doi= }}
*{{cite journal |vauthors=Bishop DF, Kornreich R, Desnick RJ |title=Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=85 |issue=11 |pages=3903–7 |year=1988 |pmid=2836863 |pmc=280328 |doi=10.1073/pnas.85.11.3903 |bibcode=1988PNAS...85.3903B }}
*{{cite journal | author=Kornreich R, Desnick RJ, Bishop DF |title=Nucleotide sequence of the human alpha-galactosidase A gene. |journal=Nucleic Acids Res. |volume=17 |issue= 8 |pages= 3301-2 |year= 1989 |pmid= 2542896 |doi= }}
*{{cite journal |vauthors=Quinn M, Hantzopoulos P, Fidanza V, Calhoun DH |title=A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A |journal=Gene |volume=58 |issue=2–3 |pages=177–88 |year=1987 |pmid=2892762 |doi=10.1016/0378-1119(87)90374-X }}
*{{cite journal | author=Bishop DF, Kornreich R, Desnick RJ |title=Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 11 |pages= 3903-7 |year= 1988 |pmid= 2836863 |doi= }}
*{{cite journal |vauthors=Bishop DF, Calhoun DH, Bernstein HS, Hantzopoulos P, Quinn M, Desnick RJ |title=Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=83 |issue=13 |pages=4859–63 |year=1986 |pmid=3014515 |pmc=323842 |doi=10.1073/pnas.83.13.4859 |bibcode=1986PNAS...83.4859B }}
*{{cite journal | author=Quinn M, Hantzopoulos P, Fidanza V, Calhoun DH |title=A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A. |journal=Gene |volume=58 |issue= 2-3 |pages= 177-88 |year= 1988 |pmid= 2892762 |doi= }}
*{{cite journal |vauthors=Lemansky P, Bishop DF, Desnick RJ, Hasilik A, von Figura K |title=Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease |journal=The Journal of Biological Chemistry |volume=262 |issue=5 |pages=2062–5 |year=1987 |pmid=3029062 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=3029062 }}
*{{cite journal  | author=Bishop DF, Calhoun DH, Bernstein HS, ''et al.'' |title=Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 13 |pages= 4859-63 |year= 1986 |pmid= 3014515 |doi= }}
*{{cite journal |vauthors=Tsuji S, Martin BM, Kaslow DC, Migeon BR, Choudary PV, Stubbleflied BK, Mayor JA, Murray GJ, Barranger JA, Ginns EI |title=Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A |journal=European Journal of Biochemistry |volume=165 |issue=2 |pages=275–80 |year=1987 |pmid=3036505 |doi=10.1111/j.1432-1033.1987.tb11438.x }}
*{{cite journal | author=Lemansky P, Bishop DF, Desnick RJ, ''et al.'' |title=Synthesis and processing of alpha-galactosidase A in human fibroblasts. Evidence for different mutations in Fabry disease. |journal=J. Biol. Chem. |volume=262 |issue= 5 |pages= 2062-5 |year= 1987 |pmid= 3029062 |doi= }}
*{{cite journal  | author=Tsuji S, Martin BM, Kaslow DC, ''et al.'' |title=Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A. |journal=Eur. J. Biochem. |volume=165 |issue= 2 |pages= 275-80 |year= 1987 |pmid= 3036505 |doi=  }}
}}
{{refend}}
{{refend}}


==External links==
==External links==
* {{MeshName|alpha-Galactosidase}}
* {{MeshName|alpha-Galactosidase}}
* {{UCSC gene info|GLA}}


{{NLM content}}
{{NLM content}}
 
{{PDB Gallery|geneid=2717}}
{{Glycoside hydrolases}}
{{Sphingolipid metabolism enzymes}}
{{Sphingolipid metabolism enzymes}}
[[Category:drug]]
{{Sugar hydrolases}}
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{{Enzymes}}
[[ru:Альфа-галактозидаза]]
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{{WH}}
[[Category:EC 3.2.1]]
{{WS}}
[[Category:Enzymes]]
[[Category:Galactosides]]

Revision as of 10:44, 27 November 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human
alpha-galactosidase
Identifiers
EC number3.2.1.22
CAS number9025-35-8
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

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.[1] Two recombinant forms of alpha-galactosidase are called agalsidase alpha (INN) and agalsidase beta (INN).

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 disease, a rare lysosomal storage disorder and sphingolipidosis that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties.[2]

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.[3]

Agalsidase alpha

The pharmaceutical company Shire manufactures agalsidase alfa (INN) under the trade name Replagal as a treatment for Fabry disease,[4] and was granted marketing approval in the EU in 2001.[5] FDA approval was applied for the United States.[6] However, in 2012, Shire withdrew their application for approval in the United States citing that the agency will require additional clinical trials before approval.[7]

Agalsidase beta

The pharmaceutical company Genzyme produces synthetic agalsidase beta (INN) under the trade name Fabrazyme for treatment of Fabry 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.[6]

Over-the-counter brand names

Alpha-galactosidase is an active ingredient in Beano, CVS BeanAid, Enzymedica's BeanAssist. These products are marketed to reduce stomach gas production after eating foods known to cause gas. There are dozens of generic brands containing the enzyme in the United States. It is optimally active at 55 degrees C, after which its half-life is 120 minutes.[8]

See also

References

  1. ↑ Calhoun DH, Bishop DF, Bernstein HS, Quinn M, Hantzopoulos P, Desnick RJ (1985). "Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A". Proceedings of the National Academy of Sciences of the United States of America. 82 (21): 7364–8. Bibcode:1985PNAS...82.7364C. doi:10.1073/pnas.82.21.7364. PMC 391345. PMID 2997789.
  2. ↑ "Entrez Gene: GLA galactosidase, alpha".
  3. ↑ Fervenza FC, Torra R, Warnock DG (December 2008). "Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease". Biologics. 2 (4): 823–43. doi:10.2147/btt.s3770. PMC 2727881. PMID 19707461.
  4. ↑ Keating GM (October 2012). "Agalsidase alfa: a review of its use in the management of Fabry disease". BioDrugs. 26 (5): 335–54. doi:10.2165/11209690-000000000-00000. PMID 22946754.
  5. ↑ "Shire Submits Biologics License Application (BLA) for REPLAGAL with the U.S. Food and Drug Administration (FDA)". FierceBiotech.
  6. ↑ 6.0 6.1 "With A Life-Saving Medicine In Short Supply, Patients Want Patent Broken". 2010-08-04. Archived from the original on 14 September 2010. Retrieved 2010-09-02.
  7. ↑ Grogan K (2012-03-15). "Shire withdraws Replagal in USA as FDA wants more trials". PharmaTimes. Archived from the original on 2014-08-19.
  8. ↑ Patil AG, K PK, Mulimani VH, Veeranagouda Y, Lee K (2010). "alpha-Galactosidase from Bacillus megaterium VHM1 and its application in removal of flatulence-causing factors from soymilk". Journal of Microbiology and Biotechnology. 20 (11): 1546–54. doi:10.4014/jmb.0912.12012. PMID 21124061.

Further reading

External links

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

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