Glucocerebrosidase

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GBA
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GBA, GBA1, GCB, GLUC, glucosylceramidase beta, Glucocerebrosidase
External IDs OMIM: 606463 MGI: 95665 HomoloGene: 68040 GeneCards: 2629
RNA expression pattern
PBB GE GBA 209093 s at tn.png

PBB GE GBA 210589 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001077411
NM_008094

RefSeq (protein)

NP_000148.2
NP_001005741.1
NP_001005742.1
NP_001165282.1
NP_001165283.1

NP_001070879.1
NP_032120.1

Location (UCSC) Chr 1: 155.23 – 155.24 Mb Chr 3: 89.2 – 89.21 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

β-Glucocerebrosidase (also called acid β-glucosidase, D-glucosyl-N-acylsphingosine glucohydrolase, or GCase) is an enzyme with glucosylceramidase activity (EC 3.2.1.45) that is needed to cleave, by hydrolysis, the beta-glucosidic linkage of the chemical glucocerebroside, an intermediate in glycolipid metabolism. It is localized in the lysosome and has a molecular weight of 59700 Daltons.

Clinical significance[edit]

Mutations in the glucocerebrosidase gene cause Gaucher's disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides. A related pseudogene is approximately 12 kb downstream of this gene on chromosome 1. Alternative splicing results in multiple transcript variants encoding the same protein.[1]

Mutations in the glucocerebrosidase gene are also associated with Parkinson's disease.[2][3]

Drugs[edit]

Alglucerase (Ceredase) was a version of glucocerebrosidase that was harvested from human placental tissue and then modified with enzymes.[4] It was approved by the FDA in 1991[5] and has been withdrawn from the market[6][7] due to the approval of similar drugs made with recombinant DNA technology instead of being harvested from tissue; drugs made recombinantly, since there is no concern about diseases being transmitted from the tissue used in harvesting, and are less expensive to manufacture.[4]

Recombinant glucocerebrosidases used as drugs include:[8]

See also[edit]

References[edit]

  1. ^ "Entrez Gene: GBA glucosidase, beta; acid (includes glucosylceramidase)". 
  2. ^ "PDGene". Alzheimer Research Forum. 2008-11-12. Retrieved 2008-11-13. 
  3. ^ Lwin A, Orvisky E, Goker-Alpan O, LaMarca ME, Sidransky E (January 2004). "Glucocerebrosidase mutations in subjects with parkinsonism". Molecular Genetics and Metabolism 81 (1): 70–3. doi:10.1016/j.ymgme.2003.11.004. PMID 14728994. 
  4. ^ a b c d Deegan PB, Cox TM (2012). "Imiglucerase in the treatment of Gaucher disease: a history and perspective". Drug Design, Development and Therapy 6: 81–106. doi:10.2147/DDDT.S14395. PMC 3340106. PMID 22563238. 
  5. ^ "Regulatory Matters" (PDF). WHO Drug Information 5 (3): 123–4. 1991. 
  6. ^ "Enzyme-replacement Therapy for Lysosomal Storage Disorders". Clinical Policy Bulletin Number: 0442. Aetna. 2014-08-08. 
  7. ^ "FDA Prescription and Over-the-Counter Drug Product List" (PDF). Additions/Deletions for Prescription Drug Product List. U.S. Food and Drug Administration. March 2012. 
  8. ^ Grabowski GA (2012). "Gaucher disease and other storage disorders". Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program 2012: 13–8. doi:10.1182/asheducation-2012.1.13. PMID 23233555. 
  9. ^ Yukhananov, Anna (1 May 2012). "U.S. FDA approves Pfizer/Protalix drug for Gaucher". Chicago Tribune. Reuters. Retrieved 2 May 2012. 

Further reading[edit]

  • Horowitz M, Zimran A (1994). "Mutations causing Gaucher disease". Human Mutation 3 (1): 1–11. doi:10.1002/humu.1380030102. PMID 8118460. 
  • Tayebi N, Stone DL, Sidransky E (October 1999). "Type 2 gaucher disease: an expanding phenotype". Molecular Genetics and Metabolism 68 (2): 209–19. doi:10.1006/mgme.1999.2918. PMID 10527671. 
  • Stone DL, Tayebi N, Orvisky E, Stubblefield B, Madike V, Sidransky E (2000). "Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease". Human Mutation 15 (2): 181–8. doi:10.1002/(SICI)1098-1004(200002)15:2<181::AID-HUMU7>3.0.CO;2-S. PMID 10649495. 
  • Caillaud C, Poenaru L (2002). "[Gaucher's and Fabry's diseases: biochemical and genetic aspects]". Journal De La Société De Biologie 196 (2): 135–40. PMID 12360742. 
  • Fabrega S, Durand P, Mornon JP, Lehn P (2002). "[The active site of human glucocerebrosidase: structural predictions and experimental validations]". Journal De La Société De Biologie 196 (2): 151–60. PMID 12360744. 
  • Alfonso P, Aznarez S, Giralt M, Pocovi M, Giraldo P (2007). "Mutation analysis and genotype/phenotype relationships of Gaucher disease patients in Spain". Journal of Human Genetics 52 (5): 391–6. doi:10.1007/s10038-007-0135-4. PMID 17427031. 

External links[edit]