A ganglioside is a molecule composed of a glycosphingolipid (

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make u ...

and oligosaccharide) with one or more sialic acids (e.g. ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative of the carbohydrate sialic acid, makes the head groups of gangliosides anionic at pH 7, which distinguishes them from globosides. The name ''ganglioside'' was first applied by the German scientist

Ernst Klenk Ernst Klenk (14 October 1896, Pfalzgrafenweiler – 29 December 1971, Cologne) was a German biochemist, known as a pioneer in research on biolipids, their metabolism, and diseases caused by biolipid disorders. Biography Klenk's father had a farm ...

in 1942 to lipids newly isolated from ganglion cells of the brain. More than 60 gangliosides are known, which differ from each other mainly in the position and number of

NANA Nana, Nanna, Na Na or NANA may refer to: People and fictional characters * Nana (given name), including a list of people and characters with the given name * Nana (surname), including a list of people and characters with the surname * Nana ( ...

residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applie ...

s. It is a component of the cell plasma membrane that modulates cell signal transduction events, and appears to concentrate in lipid rafts. Recently, gangliosides have been found to be highly important molecules in

immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see ther ...

. Natural and semisynthetic gangliosides are considered possible therapeutics for neurodegenerative disorders.

Location

Gangliosides are present and concentrated on cell surfaces, with the two hydrocarbon chains of the ceramide moiety embedded in the plasma membrane and the oligosaccharides located on the extracellular surface, where they present points of recognition for extracellular molecules or surfaces of neighboring cells. They are found predominantly in the nervous system where they constitute 6% of all phospholipids.

Function

The oligosaccharide groups on gangliosides extend well beyond the surfaces of the cell membranes, and act as distinguishing surface markers that can serve as specific determinants in cellular recognition and cell-to-cell communication. These carbohydrate head groups also act as specific receptors for certain pituitary glycoprotein

hormones A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required fo ...

and certain bacterial protein toxins such as

cholera toxin Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is AB5 multimeric protein complex secreted by the bacterium ''Vibrio cholerae''. CTX is responsible for the massive, watery diarrhea characteristic of cholera i ...

. The functions of gangliosides as specific determinants suggest its important role in the growth and differentiation of tissues as well as in

carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...

. It has been found that tumor formation can induce the synthesis of a new complement of ganglioside, and very low concentrations of a specific ganglioside can induce differentiation of cultured neuronal tumor cells.

Common gangliosides

* One

("M") **

GM1 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 ...

** GM2 **

GM3 GM3 (monosialodihexosylganglioside) is a type of ganglioside. The letter G refers to ganglioside, and M is for monosialic acid as it has one sialic acid only. The numbering is based on its relative mobility in electrophoresis among other monosi ...

* Two NANAs ("D") ** GD1a ** GD1b **

GD2 GD2 is a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues, principally to the cerebellum and peripheral nerves in humans. The rela ...

** GD3 * Three NANAs ("T") ** GT1b ** GT3 * 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(?) = N-Acetyl-D-galactose-beta-1,4- -Acetylneuraminidate- alpha-2,3-Galactose-beta-1,4-glucose-alpha-ceramide
GM2b(?) = aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer
GM1,GM1a = bDGalp(1-3)bDGalNAc Neu5Ac(2-3)DGalp(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) Neu5Ac(2-8)aNeu5Ac(2-3)DGalp(1-4)bDGlcp(1-1)Cer
GD1a = aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4) Neu5Ac(2-3)DGalp(1-4)bDGlcp(1-1)Cer
GD1alpha = aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4)

Neu5Ac(2-6) ''N''-Acetylneuraminic acid (Neu5Ac or NANA) is the predominant sialic acid found in human cells, and many mammalian cells. Other forms, such as N-Glycolylneuraminic acid, may also occur in cells. This residue is negatively charged at physiolog ...

DGalp(1-4)bDGlcp(1-1)Cer
GD1b = bDGalp(1-3)bDGalNAc(1-4) Neu5Ac(2-8)aNeu5Ac(2-3)DGalp(1-4)bDGlcp(1-1)Cer
GT1a = aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4) Neu5Ac(2-3)DGalp(1-4)bDGlcp(1-1)Cer
GT1,GT1b = aNeu5Ac(2-3)bDGalp(1-3)bDGalNAc(1-4) Neu5Ac(2-8)aNeu5Ac(2-3)DGalp(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) Neu5Ac(2-8)aNeu5Ac(2-8)aNeu5Ac(2-3)DGalp(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) Neu5Ac(2-8)aNeu5Ac(2-3)DGalp(1-4)bDGlcp(1-1)Cer
GGal = aNeu5Ac(2-3)bDGalp(1-1)Cer where * aNeu5Ac = N-acetyl-alpha-neuraminic acid * aNeu5Ac9Ac = N-acetyl-9-O-acetylneuraminic acid * bDGalp = beta-D-galactopyranose * bDGalpNAc = N-acetyl-beta-D-galactopyranose * bDGlcp = beta-D-glucopyranose * Cer = ceramide (general N-acylated sphingoid)

Pathology

Gangliosides are continuously synthesized and degraded in cells. They are degraded to ceramides by sequential removal of sugar units in the oligosaccharide group, catalyzed by a set of highly specific

lysosomal A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane pro ...

enzymes. Mutations in genes coding for these enzymes leads to the accumulation of partially broken down gangliosides in lysosomes, which results in a group of diseases called gangliosidosis. For example, the fatal

Tay–Sachs disease Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around three to six months of age, with the baby ...

arises as a genetic defect which leads to no functional hexosaminidase A produced, causing GM2 to accumulate in lysosomes. Ultimately the ganglion cells in the nervous system swell enormously, disturbing the normal functions of neurons. Sphingolipidoses

Gangliosides are also involved in several diseases: * Influenza, in which haemagglutinin of influenza virus exploits certain gangliosides to enter and infect the cells expressing them. * Guillain–Barré syndrome, which has been linked to the production of anti-ganglioside

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

. *

Cholera Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...

Tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...

Botulism Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium ''Clostridium botulinum''. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weaknes ...

Leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve dam ...

* Obesity, where inadequate ganglioside expression in mediobasal hypothalamic neurons deregulates neuronal leptin and insulin signaling.

References

External links

*
Overview of gangliosides at lipidlibrary.co.uk

{{Autoantigens Glycolipids