Alpha-galactosidase

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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alpha-galactosidase
Identifiers
EC number3.2.1.22
CAS number9025-35-8
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

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 human alpha-galactosidase are called agalsidase alpha (INN) and agalsidase beta (INN). A mold-derived form is the primary ingredient in gas relief supplements.

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 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

The pharmaceutical company Shire manufactures agalsidase alfa (INN) under the trade name Replagal as a treatment for Fabry 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 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 derived from aspergillus niger (a common mold) is an active ingredient in products marketed 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]

There are scores of supplements containing the enzyme over the counter in the United States and many more world wide. Products with Alpha-galactosidase include:

  • Beano
  • CVS BeanAid
  • Enzymedica's BeanAssist
  • Gasfix

See also

References

  1. Calhoun DH, Bishop DF, Bernstein HS, Quinn M, Hantzopoulos P, Desnick RJ (1985). "Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A". Proceedings of the National Academy of Sciences of the United States of America. 82 (21): 7364–8. Bibcode:1985PNAS...82.7364C. 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. 6.0 6.1 "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. Archived from the original on 2014-08-19.
  8. Patil AG, K PK, Mulimani VH, Veeranagouda Y, Lee K (2010). "alpha-Galactosidase from Bacillus megaterium VHM1 and its application in removal of flatulence-causing factors from soymilk". Journal of Microbiology and Biotechnology. 20 (11): 1546–54. doi:10.4014/jmb.0912.12012. PMID 21124061.

Further reading

External links

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


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