Alpha-galactosidase

Galactosidase, alpha
PDB rendering based on 1r46.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1R46, 1R47, 3GXN, 3GXP, 3GXT, 3HG2, 3HG3, 3HG4, 3HG5, 3LX9, 3LXA, 3LXB, 3LXC, 3S5Y, 3S5Z, 3TV8, 4NXS
Identifiers
Symbols	GLA ; GALA
External IDs	OMIM: 300644 MGI: 1347344 HomoloGene: 90852 ChEMBL: 2524 GeneCards: GLA Gene
EC number	3.2.1.22
Gene ontology Molecular function • catalytic activity • alpha-galactosidase activity • receptor binding • protein binding • hydrolase activity • galactoside binding • protein homodimerization activity • raffinose alpha-galactosidase activity Cellular component • extracellular region • cytoplasm • lysosome • Golgi apparatus • lysosomal lumen • extracellular exosome Biological process • sphingolipid metabolic process • glycosphingolipid metabolic process • oligosaccharide metabolic process • glycoside catabolic process • small molecule metabolic process • negative regulation of nitric oxide biosynthetic process • glycosylceramide catabolic process • glycosphingolipid catabolic process • negative regulation of nitric-oxide synthase activity Sources: Amigo / QuickGO
RNA expression pattern
File: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	Template:CAS
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
Search PMC articles PubMed articles NCBI proteins

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).

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, 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.

See also

• Beta-galactosidase
• Classification of α-galactosidases (according to CAZy)

Further reading

• Republished as:

External links

• alpha-Galactosidase at the US National Library of Medicine Medical Subject Headings (MeSH)

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