Glycosphingolipid

Introduction of Glycosphingolipid

Observed from the cell membranes from bacteria to humans, Glycosphingolipids (GSLs) are a subclass of glycolipids containing the amino alcohol sphingosine. As sphingolipids with an attached carbohydrate, GSLs are composed of a hydrophobic ceramide part and a glycosidically bound carbohydrate part. The hydrophobic ceramide part also contains a sphingoid base with a fatty acid amide at the C-2 amine. The fatty acid components of ceramides vary widely, thereby increasing diversity of GSL structures. β-linked galactose (GalCer) and glucose (GlcCer) are important sugars related to ceramide. What’s more, most members of the GSLs family are built on GlcCer, while GlcCer is abundant in certain tissues.

Generally speaking, glycosphingolipids can be divided into three categories, which are neutral glycosphingolipids, sialylated glycosphingolipids, and sulfated glycosphingolipids.

Fig.1 Typical GSL structure.¹

Biosynthesis, Trafficking, and Degradation of Glycosphingolipid

The biosynthesis of glycosphingolipids is done in a stepwise manner. Ceramide is always synthesized on the cytoplasmic face of the endoplasmic reticulum (ER), then a single sugar is added to the ceramide, and finally, the sugar is transferred from the nucleotide sugar donor under the action of glycosyltransferase. In summary, the expression pattern of GSL is determined by the expression and intracellular distribution of enzymes required for its biosynthesis. Under the action of lysosomal hydrolase, GSL is finally broken down into individual components, which can then be reused. The absence of any glycosidase can cause lysosomal storage disease.

Fig.2 Main core structures of GSLs found in vertebrates and invertebrates.¹

GSL Series in Vertebrates

• Ganglio-series GSLs predominate in the brain.
• Neolacto-series glycolipids are common on certain hematopoietic cells.
• Lacto-series glycolipids are prominent in secretory organs.
• Globo-series glycolipids are abundant in erythrocytes.

Associated Diseases of Glycosphingolipid

The mutation in glycosphingolipid biosynthetic genes results in devastating effects and critical diseases. The ST3GAL5 mutation for the biosynthesis of ganglioside leads to severe infantile seizures. The B4GALNT1 mutation for the biosynthesis of GM2 and GD2 may result in hereditary spastic paraplegia. Mutations in GSL degrading genes cause GSL storage diseases, such as Gaucher disease. In addition, anti-GSL antibodies are involved in certain autoimmune diseases.

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Reference

1. Cummings, Richard D. "Glycosphingolipids in human parasites." FEBS Open Bio 13.9 (2023): 1625-1635. Distributed under Open Access license CC BY 4.0, without modification.

Resources

• N-glycans
• O-glycans
• GPI-anchored Glycoprotein
• Glycosaminoglycans and Proteoglycans