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.

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.

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)

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.
 * Cholera toxin
 * Clostridium tetani