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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 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.^[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 alfa

The pharmaceutical company Shire manufactures agalsidase alfa (INN) under the trade name Replagal as a treatment for Fabry's 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'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.^[6]

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.^[8]

References

^ Calhoun DH, Bishop DF, Bernstein HS, Quinn M, Hantzopoulos P, Desnick RJ (November 1985). "Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A". Proc. Natl. Acad. Sci. U.S.A. 82 (21): 7364–8. doi:10.1073/pnas.82.21.7364. PMC 391345. PMID 2997789.
^ "Entrez Gene: GLA galactosidase, alpha".
^ 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.
^ 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.
^ "Shire Submits Biologics License Application (BLA) for REPLAGAL with the U.S. Food and Drug Administration (FDA)". FierceBiotech.
^ ^a ^b "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.
^ Grogan K (2012-03-15). "Shire withdraws Replagal in USA as FDA wants more trials". PharmaTimes.
^ http://www.ncbi.nlm.nih.gov/pubmed/21124061

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

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PMC	articles
PubMed	articles
NCBI	proteins

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

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
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　　[★]

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

[pmid2997789-1] Calhoun DH, Bishop DF, Bernstein HS, Quinn M, Hantzopoulos P, Desnick RJ (November 1985). "Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A". Proc. Natl. Acad. Sci. U.S.A. 82 (21): 7364–8. doi:10.1073/pnas.82.21.7364. PMC 391345. PMID 2997789.

[2] "Entrez Gene: GLA galactosidase, alpha".

[pmid19707461-3] 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.

[pmid22946754-4] 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.

[url_FierceBiotech-5] "Shire Submits Biologics License Application (BLA) for REPLAGAL with the U.S. Food and Drug Administration (FDA)". FierceBiotech.

[npr-6] "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.

[www.pharmatimes.com-7] Grogan K (2012-03-15). "Shire withdraws Replagal in USA as FDA wants more trials". PharmaTimes.

[8] ttp://www.ncbi.nlm.nih.gov/pubmed/21124061

匿名

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案内

案内

Fabrazyme