World Library  
Flag as Inappropriate
Email this Article

Gm1

Article Id: WHEBN0005872745
Reproduction Date:

Title: Gm1  
Author: World Heritage Encyclopedia
Language: English
Subject: GM1 gangliosidoses, Glycolipids, Gangliosidosis, Glucocerebroside, GM
Collection: Glycolipids
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Gm1

GM1
Names
IUPAC name
(2S,4S,5R,6R)-5-acetamido-2-[(2S,3R,4R,5S,6R)-5-[(2S,3R,4R,5R,6R)-3-acetamido-5-hydroxy-6-(hydroxymethyl)-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-2-[(2R,3S,4R,5R,6R)-4,5-dihydroxy-6-[(E,2R,3S)-3-hydroxy-2-(icosanoylamino)icos-4-enoxy]-2-(hydroxymethyl)oxan-3-yl]oxy-3-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
Other names
Monosialotetrahexosylganglioside
Identifiers
 Y
ChemSpider  Y
Jmol-3D images Image
MeSH
PubChem
Properties
C77H139N3O31
Molar mass 1,602.95 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 Y  (: Y/N?)

GM1 (monosialotetrahexosylganglioside) the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain. Besides its function in the physiology of the brain, GM1 acts as the site of binding for both Cholera toxin and E. coli heat-labile enterotoxin (Traveller's diarrhea).[1][2]

Contents

  • GM1 and Inherited Disease 1
  • GM1 and Acquired Disease 2
  • GM1 and the cholera toxin 3
  • Therapeutic applications 4
  • Additional images 5
  • References 6

GM1 and Inherited Disease

Galactosidases are enzymes that breakdown GM1, and the failure to remove GM1 results in GM1 gangliosidosis.[3] GM1 gangliosidosis are inherited disorders that progressively destroys neurons in the brain and spinal cord as GM1 accumulates. Without treatment, this results in developmental decline and muscle weakness, eventually leading to severe retardation and death.

GM1 and Acquired Disease

Antibodies to GM1 are increased in Guillain-Barré syndrome, dementia and lupus but their function is not clear.[4] There is some evidence to suggest antibodies against GM1 are associated with diarrhea in Guillain-Barré syndrome.[5]

GM1 and the cholera toxin

The bacteria Vibrio cholerae produces a multimeric toxin called the cholera toxin. The secreted toxin attaches to the surface of the host mucosa cell by binding to GM1 gangliosides. GM1 consists of a sialic acid-containing oligosaccharide covalently attached to a ceramide lipid. The A1 subunit of this toxin will gain entry to intestinal epithelial cells with the assistance of the B subunit via the GM1 ganglioside receptor. Once inside, the A1 subunit will ADP ribosylate the Gs alpha subunit which will prevent its GTPase activity. This will lock it in the active state and it will continuously stimulate adenylate cyclase. The sustained adenylate cyclase activity will lead to a sustained increase of cAMP which will cause electrolyte and water loss, causing diarrhea.

Fortunately, the SGLT1 receptor is present in the small intestine. When the cholera patient is given a solution containing water, sodium and glucose, the SGLT1 receptor will reabsorb sodium and glucose, while water will be passively absorbed with the sodium. This will replace the water and electrolyte loss in the cholera-induced diarrhea.

Therapeutic applications

Because of GM1's close role in neurotrophic repair mechanisms, it has been investigated as a potential method to potentially slow or even reverse the progression of a wide range of neurodegenerative conditions. Controlled phase II studies have indicated that GM1 can ease the symptoms of Parkinson's Disease, presumidly by countering degeneration of the substantia nigra,[6] and a similar methodolgy has been pursued to try and limit cellular damage from necrosis and apoptosis occurring after acute spinal cord injury.[7]

Additional images

References

  1. ^ Mocchetti I (2005). "Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins". Cell. Mol. Life Sci. 62 (19–20): 2283–94.  
  2. ^ Chen JC, Chang YS, Wu SL; et al. (September 2007). "Inhibition of Escherichia coli heat-labile enterotoxin-induced diarrhea by Chaenomeles speciosa". J Ethnopharmacol 113 (2): 233–9.  
  3. ^ U.S. National Library of Medicine. "GM1 gangliosidosis". Genetic Home Reference. Retrieved 26 October 2013. 
  4. ^ Bansal AS, Abdul-Karim B, Malik RA; et al. (1994). "IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls". J. Clin. Pathol. 47 (4): 300–2.  
  5. ^ Irie S, Saito T, Kanazawa N; et al. (1997). "Relationships between anti-ganglioside antibodies and clinical characteristics of Guillain-Barré syndrome". Intern. Med. 36 (9): 607–12.  
  6. ^ Thomas Jefferson University (December 2012). "GM1 Ganglioside Effects on Parkinson's Disease". Clinical Trials.gov. 
  7. ^ McDonald, John (September 1999). "Repairing the Damaged Spinal Cord". Scientific American: 69. 
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.