Alpha-galactosidase is a glycoside hydrolaseenzyme that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. It is encoded by the GLA gene. 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.
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.
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.
The pharmaceutical company Shire manufactures agalsidase alfa (INN) under the trade nameReplagal as a treatment for Fabry 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.
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.
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.
There are scores of supplents containing the enzyme over the counter in the United States and many more world wide. Products with Alpha-galactosidase include:
^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. PMID21124061.
Naumov DG (2004). "[Phylogenetic analysis of alpha-galactosidases of the GH27 family]". Molekuliarnaia Biologiia (in Russian). 38 (3): 463–76. PMID15285616. Republished as: Naumoff, D. G. (2004). "Phylogenetic Analysis of α-Galactosidases of the GH27 Family". Molecular Biology. 38 (3): 388–400. doi:10.1023/B:MBIL.0000032210.97006.de.
Eng CM, Desnick RJ (1994). "Molecular basis of Fabry disease: mutations and polymorphisms in the human alpha-galactosidase A gene". Human Mutation. 3 (2): 103–11. doi:10.1002/humu.1380030204. PMID7911050.
Caillaud C, Poenaru L (2002). "Maladies de Gaucher et de Fabry: aspects biochimiques et génétiques" [Gaucher's and Fabry's diseases: biochemical and genetic aspects]. Journal De La SociéTé De Biologie (in French). 196 (2): 135–40. doi:10.1051/jbio/2002196020135. PMID12360742. INIST:13891620.
Germain DP (2002). "Maladie de Fabry (déficit en alpha-galactosidase A): Physiopathologie, signes cliniques et aspects génétiques" [Fabry's disease (alpha-galactosidase-A deficiency): physiopathology, clinical signs, and genetic aspects]. Journal De La SociéTé De Biologie (in French). 196 (2): 161–73. PMID12360745. INIST:13891623.
Schaefer E, Mehta A, Gal A (2005). "Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey". Acta Paediatrica. 94 (447): 87–92; discussion 79. doi:10.1080/08035320510031045. PMID15895718.
Lidove O, Joly D, Barbey F, Bekri S, Alexandra JF, Peigne V, Jaussaud R, Papo T (2007). "Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature". International Journal of Clinical Practice. 61 (2): 293–302. doi:10.1111/j.1742-1241.2006.01237.x. PMID17263716.
Ishii S, Sakuraba H, Suzuki Y (1992). "Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease". Human Genetics. 89 (1): 29–32. doi:10.1007/BF00207037. PMID1315715.
von Scheidt W, Eng CM, Fitzmaurice TF, Erdmann E, Hübner G, Olsen EG, Christomanou H, Kandolf R, Bishop DF, Desnick RJ (1991). "An atypical variant of Fabry's disease with manifestations confined to the myocardium". The New England Journal of Medicine. 324 (6): 395–9. doi:10.1056/NEJM199102073240607. PMID1846223.
Koide T, Ishiura M, Iwai K, Inoue M, Kaneda Y, Okada Y, Uchida T (1990). "A case of Fabry's disease in a patient with no alpha-galactosidase A activity caused by a single amino acid substitution of Pro-40 by Ser". FEBS Letters. 259 (2): 353–6. doi:10.1016/0014-5793(90)80046-L. PMID2152885.
Quinn M, Hantzopoulos P, Fidanza V, Calhoun DH (1987). "A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A". Gene. 58 (2–3): 177–88. doi:10.1016/0378-1119(87)90374-X. PMID2892762.
Tsuji S, Martin BM, Kaslow DC, Migeon BR, Choudary PV, Stubbleflied BK, Mayor JA, Murray GJ, Barranger JA, Ginns EI (1987). "Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A". European Journal of Biochemistry. 165 (2): 275–80. doi:10.1111/j.1432-1033.1987.tb11438.x. PMID3036505.