Alpha-galactosidase

Alpha-galactosidase is a is_associated_with::glycoside hydrolase is_associated_with::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).

Function
This enzyme is a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. It predominantly hydrolyzes is_associated_with::ceramide trihexoside, and it can catalyze the hydrolysis of is_associated_with::melibiose into galactose and glucose.

Pathology
A variety of mutations in this gene affect the synthesis, processing, and stability of this enzyme, which causes is_associated_with::Fabry's disease, a rare is_associated_with::lysosomal storage disorder and is_associated_with::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 is_associated_with::oligosaccharide side chains.

Agalsidase alfa
The pharmaceutical company Shire manufactures agalsidase alfa (INN) under the is_associated_with::trade name is_associated_with::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 is_associated_with::Genzyme produces synthetic agalsidase beta (INN) under the trade name Fabrazyme for treatment of Fabry's disease. In 2009, contamination at Genzyme's is_associated_with::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 is_associated_with::Bayh–Dole Act.

Over-the-counter brand names
Alpha-galactosidase is an active ingredient in Beano, Suntaqzyme, Bean-zyme, and Gas-zyme 3x, 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.