Alpha-galactosidase

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Galactosidase, alpha

PDB rendering based on 1r46.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GLA ; GALA
External IDs OMIM300644 MGI1347344 HomoloGene90852 ChEMBL: 2524 GeneCards: GLA Gene
EC number 3.2.1.22
RNA expression pattern
PBB GE GLA 214430 at tn.png
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

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]

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]

References[edit]

  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". 
  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. 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. ^ 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. 
  7. ^ Grogan K (2012-03-15). "Shire withdraws Replagal in USA as FDA wants more trials". PharmaTimes. 

Further reading[edit]

External links[edit]

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