Aglucosidase alfa consists of the human enzyme acid alpha-glucosidase (GAA) which is essential for the degradation of glygogen to glucose in lysosomes. It is encoded by the most predominant of nine observed haplotypes of this gene. Aglucosidase alfa is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Alglucosidase alfa degrades glycogen by catalyzing the hydrolysis of a-1,4- and a-1,6- glycosidic linkages of lysosomal glycogen. Structurally, Alglucosidase alfa is a glycoprotein with a calculated mass of 98,008 daltons for the 883 residue mature polypeptide chain, and a total mass of approximately 109,000 daltons, including carbohydrates. It is used for the treatment of Pompe disease (GAA deficiency) in infants and pediatric patients.
|Protein chemical formula||C4435H6739N1175O1279S32|
|Protein average weight||105270.802 Da|
>Alglucosidase alfa AHPGRPRAVPTQCDVPPNSRFDCAPDKAITQEQCEARGCCYIPAKQGLQGAQMGQPWCFF PPSYPSYKLENLSSSEMGYTATLTRTTPTFFPKDILTLRLDVMMETENRLHFTIKDPANR RYEVPLETPHVHSRAPSPLYSVEFSEEPFGVIVRRQLDGRVLLNTTVAPLFFADQFLQLS TSLPSQYITGLAEHLSPLMLSTSWTRITLWNRDLAPTPGANLYGSHPFYLALEDGGSAHG VFLLNSNAMDVVLQPSPALSWRSTGGILDVYIFLGPEPKSVVQQYLDVVGYPFMPPYWGL GFHLCRWGYSSTAITRQVVENMTRAHFPLDVQWNDLDYMDSRRDFTFNKDGFRDFPAMVQ ELHQGGRRYMMIVDPAISSSGPAGSYRPYDEGLRRGVFITNETGQPLIGKVWPGSTAFPD FTNPTALAWWEDMVAEFHDQVPFDGMWIDMNEPSNFIRGSEDGCPNNELENPPYVPGVVG GTLQAATICASSHQFLSTHYNLHNLYGLTEAIASHRALVKARGTRPFVISRSTFAGHGRY AGHWTGDVWSSWEQLASSVPEILQFNLLGVPLVGADVCGFLGNTSEELCVRWTQLGAFYP FMRNHNSLLSLPQEPYSFSEPAQQAMRKALTLRYALLPHLYTLFHQAHVAGETVARPLFL EFPKDSSTWTVDHQLLWGEALLITPVLQAGKAEVTGYFPLGTWYDLQTVPVEALGSLPPP PAAPREPAIHSEGQWVTLPAPLDTINVHLRAGYIIPLQGPGLTTTESRQQPMALAVALTK GGEARGELFWDDGESLEVLERGAYTQVIFLARNNTIVNELVRVTSEGAGLQLQKVTVLGV ATAPQQVLSNGVPVSNFTYSPDTKVLDICVSLLMGEQFLVSWCDownload FASTA Format
|External IDs||Not Available|
|Product Ingredients||Not Available|
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|International Brands||Not Available|
|Brand mixtures||Not Available|
For the treatment of Pompe disease (GAA deficiency) in infants and pediatric patients.
Pompe disease (glycogen storage disease type II, GSD II, glycogenosis type II, acid maltase deficiency) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA. In the infantile-onset form, Pompe disease results in intralysosomal accumulation of glycogen in various tissues, particularly cardiac and skeletal muscles, and hepatic tissues, leading to the development of cardiomyopathy, progressive muscle weakness, and impairment of respiratory function. In the juvenile- and adult-onset forms, intralysosomal accumulation of glycogen is limited primarily to skeletal muscle, resulting in progressive muscle weakness. Death in all forms is usually related to respiratory failure. Alglucosidase alfa provides an exogenous source of GAA. Binding to mannose-6-phosphate receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen.
|Mechanism of action|
Alglucosidase alfa is designed to act as an exogenous source of GAA, acting to correct GAA deficiency that is the hallmark of Pompe disease. Alglucosidase alfa binds to mannose-6-phosphate receptors on the cell surface via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen. Specifically, it hydrolyses alpha-1,4-glucose bonds.
|Volume of distribution|
|Protein binding||Not Available|
|Route of elimination|
Via kidney and liver
2.3 ± 0.4 hours.
There have been no reports of overdose with alglucosidase alfa.
|Pharmacogenomic Effects/ADRs||Not Available|
|Drug Interactions||No interactions found.|
|Food Interactions||Not Available|
|Synthesis Reference||Not Available|
|ATC Codes||A16AB07 — Alglucosidase alfa|
|PDB Entries||Not Available|
|FDA label||Download (1.11 MB)|
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
|Experimental Properties||Not Available|
|Super Class||Organic Acids|
|Class||Carboxylic Acids and Derivatives|
|Sub Class||Amino Acids, Peptides, and Analogues|
|Alternative Parents||Not Available|
|Molecular Framework||Not Available|
|External Descriptors||Not Available|
- Pharmacological action
- General Function:
- Transmembrane signaling receptor activity
- Specific Function:
- Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex.
- Gene Name:
- Uniprot ID:
- Molecular Weight:
- 30993.06 Da
- Chavez CA, Bohnsack RN, Kudo M, Gotschall RR, Canfield WM, Dahms NM: Domain 5 of the cation-independent mannose 6-phosphate receptor preferentially binds phosphodiesters (mannose 6-phosphate N-acetylglucosamine ester). Biochemistry. 2007 Nov 6;46(44):12604-17. Epub 2007 Oct 10. [PubMed:17927214 ]
- Pharmacological action
- Hu D, Kamiya Y, Totani K, Kamiya D, Kawasaki N, Yamaguchi D, Matsuo I, Matsumoto N, Ito Y, Kato K, Yamamoto K: Sugar-binding activity of the MRH domain in the ER alpha-glucosidase II beta subunit is important for efficient glucose trimming. Glycobiology. 2009 Oct;19(10):1127-35. doi: 10.1093/glycob/cwp104. Epub 2009 Jul 22. [PubMed:19625484 ]
- Christiansen C, Hachem MA, Glaring MA, Vikso-Nielsen A, Sigurskjold BW, Svensson B, Blennow A: A CBM20 low-affinity starch-binding domain from glucan, water dikinase. FEBS Lett. 2009 Apr 2;583(7):1159-63. doi: 10.1016/j.febslet.2009.02.045. Epub 2009 Mar 9. [PubMed:19275898 ]