gangliosides

Gangliosides are a class of glycosphingolipids characterized by the presence of one or more sialic acid residues in their oligosaccharide headgroups. They consist of a ceramide lipid tail attached to a highly branched sugar chain that is typically terminated or heavily decorated with N-acetylneuraminic acid. Because of the acidic sialic acids, gangliosides carry a negative charge at physiological pH and are enriched in the outer leaflet of the plasma membrane, particularly in neurons.

Gangliosides are commonly classified into series designated by letters (M, D, T, Q) that reflect the number of sialic acids, with GM, GD, GT, and GQ naming for monosialogangliosides through tetrasialogangliosides. Examples include GM1, GM2, GM3; GD1a, GD1b, GD2; GT1b and GQ1b. The M, D, T, and Q prefixes indicate monosialo, disialo, trisialo, and tetrasialo forms, respectively.

Functions attributed to gangliosides include participation in cell–cell recognition, modulation of receptor function, and involvement in neurodevelopment, synaptic transmission, and membrane organization. They participate in organized membrane microdomains and can serve as receptors or co-receptors for certain bacterial toxins and viruses, the best known example being the interaction of cholera toxin with GM1.

Biosynthesis occurs in the Golgi apparatus, where a ceramide molecule is extended by glycosyltransferases to form the core glycosphingolipid and successive sialyltransferases add sialic acid residues. The CMP-sialic acid donor is produced in the cytosol and transported into the Golgi lumen. Once assembled, gangliosides are transported to the plasma membrane via vesicular trafficking.

Clinically, ganglioside metabolism is linked to several lysosomal storage diseases. Defects in specific hydrolases lead to accumulation of particular gangliosides, most notably GM2 in Tay-Sachs and Sandhoff diseases, due to deficiency of β-hexosaminidase A (and B in Sandhoff).