Fabrazyme

アガルシダーゼベータ。ファブラザイム

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/10 12:41:28」(JST)

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Galactosidase, alpha
PDB rendering based on 1r46.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1R46, 1R47, 3GXN, 3GXP, 3GXT, 3HG2, 3HG3, 3HG4, 3HG5, 3LX9, 3LXA, 3LXB, 3LXC, 3S5Y, 3S5Z, 3TV8
Identifiers
Symbols	GLA ; GALA
External IDs	OMIM: 300644 MGI: 1347344 HomoloGene: 90852 ChEMBL: 2524 GeneCards: GLA Gene
EC number	3.2.1.22
Gene ontology Molecular function • catalytic activity • alpha-galactosidase activity • receptor binding • protein binding • hydrolase activity • galactoside binding • protein homodimerization activity • raffinose alpha-galactosidase activity Cellular component • extracellular region • cytoplasm • lysosome • Golgi apparatus • lysosomal lumen • extracellular vesicular exosome Biological process • sphingolipid metabolic process • glycosphingolipid metabolic process • oligosaccharide metabolic process • glycoside catabolic process • small molecule metabolic process • negative regulation of nitric oxide biosynthetic 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	n/a
RefSeq (mRNA)	NM_000169	NM_013463
RefSeq (protein)	NP_000160	NP_038491
Location (UCSC)	Chr HG1439_PATCH: 100.65 – 100.66 Mb	Chr X: 134.59 – 134.6 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 NCBI proteins

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. Two recombinant forms of alpha-galactosidase are called agalsidase alfa (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'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 alfa

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

Agalsidase beta

The pharmaceutical company Genzyme produces synthetic agalsidase beta (INN) under the trade 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.

Over-the-counter brand names

Alpha-galactosidase is an active ingredient in Beano, Suntaqzyme, Bean-zyme, and Gas-zyme 3x, marketed as products to reduce stomach gas production after eating foods known to cause gas. It is optimally active at 55 degrees C, after which its half-life is 120 minutes.

See also

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

References

Further reading

• Naumoff DG (2004). "Phylogenetic analysis of α-galactosidases of the GH27 family". Molecular Biology (Engl Transl) 38 (3): 388–399. doi:10.1023/b:mbil.0000032210.97006.de. 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. 
• 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. 
• 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. 
• 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. 
• 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. 
• 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. 
• 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

• alpha-Galactosidase at the US National Library of Medicine Medical Subject Headings (MeSH)

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

UpToDate Contents

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• 1. ファブリー病の治療 treatment of fabry disease
• 2. 左室肥大が認められる患者におけるファブリー病の臨床症状およびスクリーニング cardiac manifestations of fabry disease and screening in patients with left ventricular hypertrophy
• 3. ファブリー病の神経症状 neurologic manifestations of fabry disease

English Journal

• Intrafamilial phenotypic variability in four families with Anderson-Fabry disease.

• Rigoldi M, Concolino D, Morrone A, Pieruzzi F, Ravaglia R, Furlan F, Santus F, Strisciuglio P, Torti G, Parini R.SourceRare Metabolic Diseases Unit, San Gerardo Hospital, Monza, Italy.
• Clinical genetics.Clin Genet.2013 Aug 23. doi: 10.1111/cge.12261. [Epub ahead of print]
• We analysed the clinical history of 16 hemizygous males affected by Anderson-Fabry Disease, from four families, to verify their intrafamilial phenotypic variability. Seven male patients, ranging from 26 to 61 years of age, died, whereas nine (age range 23-55) are alive. Eleven patients have underg
• PMID 23980562

• Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A).

• Lin HY, Liu HC, Huang YH, Liao HC, Hsu TR, Shen CI, Li ST, Li CF, Lee LH, Lee PC, Huang CK, Chiang CC, Lin CY, Lin SP, Niu DM.SourceInstitute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
• BMJ open.BMJ Open.2013 Jul 16;3(7). pii: e003146. doi: 10.1136/bmjopen-2013-003146. Print 2013.
• OBJECTIVE: Current studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A).DESIGN: Retrospective cohort study.SETTING: Tertiary medical centre.PARTICIPANTS: 21
• PMID 23864212

• Analysis of left ventricular mass in untreated men and in men treated with agalsidase-β: data from the Fabry Registry.

• Germain DP, Weidemann F, Abiose A, Patel MR, Cizmarik M, Cole JA, Beitner-Johnson D, Benistan K, Cabrera G, Charrow J, Kantola I, Linhart A, Nicholls K, Niemann M, Scott CR, Sims K, Waldek S, Warnock DG, Strotmann J.SourceUniversity of Versailles, Hôpital Raymond Poincaré (AP-HP), Garches, France.
• Genetics in medicine : official journal of the American College of Medical Genetics.Genet Med.2013 May 23. doi: 10.1038/gim.2013.53. [Epub ahead of print]
• Purpose:The aim of this study was to evaluate the progression of left ventricular hypertrophy in untreated men with Fabry disease and to assess the effects of agalsidase-β (recombinant human α-galactosidase A) on left ventricular hypertrophy.Methods:Longitudinal Fabry Registry data were analyzed f
• PMID 23703683

Japanese Journal

• ファブリー病透析患者における酵素補充療法の治療効果と, アガルシダーゼアルファの体内動態について

• 岡田 志緒子,稲荷場 ひろみ,崔 吉永 [他],河野 仁美,寺柿 政和,岡村 幹夫,吉本 充,田中 あけみ,根来 伸夫,葭山 稔
• 日本透析医学会雑誌 = Journal of Japanese Society for Dialysis Therapy 43(11), 945-951, 2010-11-28
• ファブリー病に対して酵素補充療法（ERT）が実用化され，アガルシダーゼアルファ，アガルシダーゼベータの2剤が使用可能である．しかし，透析患者に対してのデータは少ない．特に，アガルシダーゼアルファに関しては血液透析（HD）中投与のデータがないため，HD中投与の可否につき薬物動態の検討を行った．【症例】46歳，男性．26歳時に脳梗塞を発症し，ファブリー病と診断．平成18年7月に血液透析導入，11月より …
• NAID 10027893550

Related Links

• Fabrazyme ® | Fabry Disease Enzyme Replacement Therapy ...

Learn about Fabry disease, an inherited disorder caused by deficiency of the alpha-galactosidase A enzyme, and Fabrazyme enzyme replacement therapy.

• Alpha-galactosidase - Wikipedia, the free encyclopedia

The pharmaceutical company Genzyme produces synthetic agalsidase beta under the brand name Fabrazyme for ... In 2009, contamination at Genzyme's Allston, Massachusetts plant caused a worldwide shortage of Fabrazyme, and supplies ...

Related Pictures

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★リンクテーブル★

リンク元	「アガルシダーゼベータ」

「アガルシダーゼベータ」

　　[★]

英

agalsidase beta

商

ファブラザイム Fabrazyme

商品名

• アガルシダーゼベータ

会社名

• ＪＣＲファーマ

成分

• アガルシダーゼベータ

薬効分類

• 遺伝子組換えファブリー病治療剤

薬効

• ファブリー病を効能・効果とするバイオ後続品