Entrez 2717 | Ensembl ENSG00000102393 | |
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Aliases GLA, GALA, galactosidase alpha External IDs MGI: 1347344 HomoloGene: 90852 GeneCards: GLA | ||
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. Two recombinant forms of alpha-galactosidase are called agalsidase alfa (INN) and agalsidase beta (INN).
Contents
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.
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.
Agalsidase alfa
The pharmaceutical company Shire manufactures agalsidase alfa (INN) under the trade name Replagal as a treatment for Fabry's disease, and was granted marketing approval in the EU in 2001. FDA approval was applied for the United States. However, in 2012, Shire withdrew their application for approval in the United States citing that the agency will require additional clinical trials before approval.
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.
Over-the-counter brand names
Alpha-galactosidase is an active ingredient in Beano, CVS BeanAid, and Enzymedica's BeanAssist. These products are marketed to reduce stomach gas production after eating foods known to cause gas. There are dozens of generic brands containing the enzyme in the United States. It is optimally active at 55 degrees C, after which its half-life is 120 minutes.