Ganglioside

Ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. n-acetylneuraminic acid, NANA) linked on the sugar chain. The 60+ known gangliosides differ mainly in the position and number of NANA residues.

It is a component of the cell plasma membrane that modulates cell signal transduction events. It appears that they concentrate in lipid rafts.

They have recently been found to be highly important in immunology. Natural and semisynthetic gangliosides are considered possible therapeutics for neurodegenerative disorders.^[1]

Gangliosides are more complex glycosphingolipids in which oligosaccharide chains containing N-acetylneuraminic acid (NeuNAc) are attached to a ceramide. NeuNAc, an acetylated derivative of the carbohydrate sialic acid, makes the head groups of Gangliosides anionic. NB: the M in GM2 stands for monosialo, i.e., one NeuNAc residue. GM2 is the second monosialo ganglioside characterized, thus the subscript 2. Their structural diversity results from variation in the composition and sequence of the sugar residues. In all Gangliosides, the ceramide is linked through its C-1 to a β-glucosyl residue, which, in turn, is bound to a β-galactosyl residue.

The name ganglioside was first applied by the German scientist Ernst Klenk in 1942 to lipids newly isolated from ganglion cells of brain.^[2]

Location

They are present on cell surfaces, with the 2 hydrocarbon chains of the ceramide moiety embedded in the plasma membrane and the oligosaccharides on the extracellular surface. They are found predominantly in the nervous system where they constitute 6% of all phospholipids.

They are involved in various functions including cell-to-cell contact, ion conductance, and acting as receptors.

Function

Gangliosides, glycosphingolipids, and glycoproteins found on the surface of oligosaccharide provide cells with distinguishing surface markers that can serve in cellular recognition and cell-to-cell communication. Structures similar to the ABO blood group antigens on the surface of human cells can be oligosaccharide components of glycosphingolipids in addition to being linked to proteins to form glycoproteins.

Common gangliosides

• One NANA ("M")
  • GM1
  • GM2
  • GM3

• Two NANAs ("D")
  • GD1a
  • GD1b
  • GD2
  • GD3

• Three NANAs ("T")
  • GT1b

• Four NANAs ("Q")
  • GQ1

structures of the common gangliosides

GM2-1 = aNeu5Ac(2-3)bDGalp(1-?)bDGalNAc(1-?)bDGalNAc(1-?)bDGlcp(1-1)Cer
GM3 = aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer
GM2,GM2a(?) = bDGalpNAc(1-4)[aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
GM2b(?) = aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer
GM1,GM1a = bDGalp(1-3)bDGalNAc[aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
asialo-GM1,GA1 = bDGalp(1-3)bDGalpNAc(1-4)bDGalp(1-4)bDGlcp(1-1)Cer
asialo-GM2,GA2 = bDGalpNAc(1-4)bDGalp(1-4)bDGlcp(1-1)Cer
GM1b = aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4)bDGalp(1-4)bDGlcp(1-1)Cer
GD3 = aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer
GD2 = bDGalpNAc(1-4)[aNeu5Ac(2-8)aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
GD1a = aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4)[aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
GD1alpha = aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4)[aNeu5Ac(2-6)]bDGalp(1-4)bDGlcp(1-1)Cer
GD1b = bDGalp(1-3)bDGalNAc(1-4)[aNeu5Ac(2-8)aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
GT1a = aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4)[aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
GT1,GT1b = aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4)[aNeu5Ac(2-8)aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
OAc-GT1b = aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4)aXNeu5Ac9Ac(2-8)aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
GT1c = bDGalp(1-3)bDGalNAc(1-4)[aNeu5Ac(2-8)aNeu5Ac(2-8)aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
GT3 = aNeu5Ac(2-8)aNeu5Ac(2-8)aNeu5Ac(2-3)bDGal(1-4)bDGlc(1-1)Cer
GQ1b = aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4)[aNeu5Ac(2-8)aNeu5Ac(2-3)]bDGalp(1-4)bDGlcp(1-1)Cer
GGal = aNeu5Ac(2-3)bDGalp(1-1)Cer

where
aNeu5Ac = 5-acetyl-alpha-neuraminic acid
aNeu5Ac9Ac = 5,9-diacetyl-alpha-neuraminic acid
bDGalp = beta-D-galactopyranose
bDGalpNAc = N-acetyl-beta-D-galactopyranose
bDGlcp = beta-D-glucopyranose
Cer = ceramide (general N-acylated sphingoid)

Pathobiology

Gangliosidoses

Mutations in genes coding for enzymes of ganglioside metabolism cause severe lipid storage diseases called gangliosidoses, that encomprise GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs Disease and Sandhoff disease).

The non-functioning beta-galactosidase (GM1) or hexosaminidase (GM2) causes the accumulation of gangliosides in lysosomes (lysosomal storage disease) of several cells (macrophages, neurons), disturbing their functions.

Miscellaneous

Ganglioside are also involved in several diseases:

• Haemagglutinin of Influenza virus exploits certain gangliosides to enter and infect the cells expressing them.
• Tay-Sachs Disease involves accumulation of gangliosides due to a non functioning B-N-acetyl hexosaminidase.
• Guillain-Barré syndrome has been linked to the production of anti-ganglioside antibodies.^[3]
• Cholera toxin
• Clostridium tetani

References

1. ^ Mocchetti I (2005). "Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins". Cell Mol Life Sci 62 (19–20): 2283–94. doi:10.1007/s00018-005-5188-y. PMID 16158191. 
2. ^ "Gangliosides, structure, occurrence, biology and analysis". Lipid Library. The American Oil Chemists' Society. http://lipidlibrary.aocs.org/Lipids/gang/index.htm. 
3. ^ Nachamkin I; Shadomy, SV; Moran, AP; Cox, N; Fitzgerald, C; Ung, H; Corcoran, AT; Iskander, JK et al. (2008). "Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barré syndrome". J. Infect Dis. 198 (2): 226–33. doi:10.1086/589624+10.1086/589624. PMID 18522505. 

External links

• MeSH Gangliosides
• Overview of gangliosides at lipidlibrary.co.uk
• Overview of gangliosides at cyberlipid.org