Alpha-galactosidase

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Galactosidase, alpha
PBB Protein GLA image.jpg
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 X:
101.4 – 101.41 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] Two recombinant forms of alpha-galactosidase are called agalsidase alfa (INN) and agalsidase beta (INN).

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 alfa[edit]

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[edit]

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[edit]

Alpha-galactosidase is an active ingredient in Beano, Suntaqzyme, Bean-zyme, and Gas-zyme 3x, Bloateez (India) 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]

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. 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. ^ 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. 
  8. ^ http://www.ncbi.nlm.nih.gov/pubmed/21124061

Further reading[edit]

External links[edit]

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