Glycan Biosynthesis and Function
Animal cells elaborate a large array of glycoconjugates, which are composed of one or more glycans (carbohydrate chains) covalently bound to protein or lipid backbones. Glycoconjugates form a thick layer at the cell surface through which nutrients, hormones, growth factors, and soluble proteins must diffuse to gain access to plasma membrane receptors and transporters. Cells also deposit glycoconjugates in extracellular matrices, which provide support and organization to tissues and create barriers for regulating diffusion. For many years, glycans were thought to play merely structural roles, but we now know that they participate in fundamental properties of cells, including protein quality control, cell adhesion and motility, endocytosis, and signal transduction (1, 2).
Before glycans and their protein or lipid backbones arrive at the cell surface, they must be made inside the cell. This process occurs in the lumen of the endoplasmic reticulum and the Golgi apparatus. A variety of specific biosynthetic enzymes work in a sequential manner to assemble the glycan in a linear fashion. The biosynthetic enzymes involved in these early steps, such as the protein or lipid linkage region, are responsible for assembling multiple classes of glycans. As the sequential biosynthetic process continues, the enzymes become increasingly more specific for individual classes of glycans. The enzymes involved in these late stages of the biosynthetic process are known to be highly specific with unique roles in adding a specific sugar or acid residue to a particular glycan.
- Brown JR, Crawford BE, and Esko JD. Glycan antagonists and inhibitors: a fount for drug discovery. Crit Rev Biochem Mol Biol 42: 481-515, 2007.1.
- Varki A, Cummings RD, Esko JD, Freeze HH, Hart G, and Marth JD. Essentials of Glycobiology. New York: Cold Spring Harbor Laboratory Press, 1999.
