WordNet
- to remain unmolested, undisturbed, or uninterrupted -- used only in infinitive form; "let her be"
- work in a specific place, with a specific subject, or in a specific function; "He is a herpetologist"; "She is our resident philosopher" (同)follow
- have life, be alive; "Our great leader is no more"; "My grandfather lived until the end of war" (同)live
- be identical to; be someone or something; "The president of the company is John Smith"; "This is my house"
- happen, occur, take place; "I lost my wallet; this was during the visit to my parents house"; "There were two hundred people at his funeral"; "There was a lot of noise in the kitchen"
- have the quality of being; (copula, used with an adjective or a predicate noun); "John is rich"; "This is not a good answer"
- occupy a certain position or area; be somewhere; "Where is my umbrella?" "The toolshed is in the back"; "What is behind this behavior?"
- spend or use time; "I may be an hour"
- stake on the outcome of an issue; "I bet $100 on that new horse"; "She played all her money on the dark horse" (同)wager, play
- the act of gambling; "he did it on a bet" (同)wager
- maintain with or as if with a bet; "I bet she will be there!" (同)wager
- second in order of importance; "the candidate, considered a beta male, was perceived to be unable to lead his party to victory"
- the 2nd letter of the Greek alphabet
- preliminary or testing stage of a software or hardware product; "a beta version"; "beta software"
- beets (同)genus Beta
PrepTutorEJDIC
- 《連結語として補語を伴なって…『である』,…だ,…です / 《位置・場所を表す語句を伴って》(…に)『ある』,いる(occupy a place or situation) / 〈物事が〉『存在する』,ある(exist);〈生物が〉生存する,生きている(live) / 行われる,起こる,発生する(take place, occur) / 存続する,そのままでいる(remain as before) / 《『be to』 do》 / …する予定である,…することになっている / …すべきだ / 《受動態の不定詞を伴って》…できる / 《命令》…するのだ / 《条件節に》…する意図がある / 《『if…were to』 do》…するとしたなら / 《『be』 do『ing』》《進行形》 / 《進行中の動作》…している,しつつある / 《近い未来》…しようとしている,するつもり / 《動作の反復》(いつも)…している / 《『be』+『他動詞の過去分詞』》《受動態》…される,されている / 《『be』+『自動詞の過去分詞』》《完了形》…した[状態にある]
- 『かけ』・(…との)かけ《+『with』+『名』》 / かけた物(金) / かけの対象 / 〈金・物〉'を'『かける』 / (かけ事・ゲームなどで)〈人〉‘と'『かけをする』《+『名』〈人〉+『on』+『名』》 / (…に)『かける』《+『on』(『against』)+『名』(one's do『ing』)》
- ベータ(ギリシア語アルファベットの第2文字;B,β;英語のB,b に遭当)
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/12 12:42:51」(JST)
[Wiki en表示]
| 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
|
| 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.[1]
Contents
- 1 Function
- 2 Pathology
- 2.1 Agalsidase alpha
- 2.2 Agalsidase beta
- 2.3 Brand names
- 3 See also
- 4 References
- 5 Further reading
- 6 External links
Function[edit]
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[edit]
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 alpha[edit]
The pharmaceutical company Shire manufactures agalsidase alpha under the brand 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[edit]
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.[6]
Brand names[edit]
Alpha-galactosidase is an active ingredient in Beano, Bean-zyme, and Gas-zyme 3x, marketed as products to reduce stomach gas production after eating foods known to cause gas.
See also[edit]
- Beta-galactosidase
- Classification of α-galactosidases (according to CAZy)
References[edit]
- ^ 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. 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.
Further reading[edit]
- 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.
- 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[edit]
- 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.
|
PDB gallery
|
|
|
|
|
1r46: Structure of human alpha-galactosidase
|
|
|
|
1r47: Structure of human alpha-galactosidase
|
|
|
|
|
Hydrolase: sugar hydrolases (EC 3.2)
|
|
| 3.2.1: Glycoside hydrolases |
| Disaccharidase |
- Sucrase/Sucrase-isomaltase/Invertase
- Maltase
- Trehalase
- Lactase
|
|
| Glucosidases |
- Cellulase
- Alpha-glucosidase
- Acid
- Neutral AB
- Neutral C
- Beta-glucosidase
- Debranching enzyme
|
|
| Other |
- Amylase
- Chitinase
- Lysozyme
- Neuraminidase
- NEU1
- NEU2
- NEU3
- NEU4
- Bacterial neuraminidase
- Viral neuraminidase
- Galactosidases
- alpha-Mannosidase
- Glucuronidase
- Hyaluronidase
- Pullulanase
- Glucosylceramidase
- Galactosylceramidase
- Alpha-N-acetylgalactosaminidase
- Alpha-N-acetylglucosaminidase
- Fucosidase
- Hexosaminidase
- Iduronidase
- Maltase-glucoamylase
- Heparanase
|
|
|
3.2.2: Hydrolysing
N-Glycosyl compounds |
- DNA glycosylases: Oxoguanine glycosylase
|
|
- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
|
|
|
|
|
Metabolism: lipid metabolism · glycolipid enzymes
|
|
| Sphingolipid |
|
To glycosphingolipid
|
- Glycosyltransferase · Sulfotransferase
|
|
|
To ceramide
|
- From ganglioside: Beta-galactosidase
- Hexosaminidase A
- Neuraminidase
- Glucocerebrosidase
- From globoside: Hexosaminidase B
- Alpha-galactosidase
- Beta-galactosidase
- Glucocerebrosidase
- From sphingomyelin: Sphingomyelin phosphodiesterase (Sphingomyelin phosphodiesterase 1)
- From sulfatide: Arylsulfatase A
- Galactosylceramidase
|
|
|
To sphingosine
|
- Ceramidase
- ACER1
- ACER2
- ACER3
- ASAH1
- ASAH2
- ASAH2B
- ASAH2C
|
|
|
Other
|
Sphingosine kinase
|
|
|
| NCL |
- Palmitoyl protein thioesterase
- Tripeptidyl peptidase I
- CLN3
- CLN5
- CLN6
- CLN8
|
|
| Ceramide synthesis |
- Serine C-palmitoyltransferase (SPTLC1)
- Ceramide glucosyltransferase (UGCG)
|
|
|
|
mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
|
k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
|
m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
|
|
|
|
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Antiproteinuric therapy and Fabry nephropathy: factors associated with preserved kidney function during agalsidase-beta therapy.
- Warnock DG1, Thomas CP2, Vujkovac B3, Campbell RC4, Charrow J5, Laney DA6, Jackson LL1, Wilcox WR6, Wanner C7.
- Journal of medical genetics.J Med Genet.2015 Oct 21. pii: jmedgenet-2015-103471. doi: 10.1136/jmedgenet-2015-103471. [Epub ahead of print]
- BACKGROUND: Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) i
- PMID 26490103
- Surges in proteinuria are associated with plasma GL-3 elevations in a young patient with classic Fabry disease.
- Kanai T1, Ito T2, Odaka J3, Saito T4, Aoyagi J5, Betsui H6, Yamagata T7.
- European journal of pediatrics.Eur J Pediatr.2015 Oct 10. [Epub ahead of print]
- Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in accumulations of globotriaosylceramide (GL-3) in systemic tissues. Nephropathy is a dominant feature of Fabry disease. It still remains unclear how the nephropathy prog
- PMID 26454753
Japanese Journal
- 12年間酵素補充療法を行った古典型ファブリー病１男性症例の治療成績
- Industrial Info. ファブリー病の心症状とアガルシダーゼベータによる酵素補充療法
- Treatment with agalsidase beta during pregnancy in Fabry disease
- The journal of obstetrics and gynaecology research 36(2), 428-429, 2010-04-01
- NAID 10031121634
★リンクテーブル★
[★]
- 英
- agalsidase beta
- 商
- ファブラザイム Fabrazyme
商品名
会社名
成分
薬効分類
薬効
[★]
β、ベータ
[★]