FIGURE 2.

The biosynthesis of CS and DS chains showing their diverse disaccharide glycoforms that are functional in the juvenile and adult CNS/PNS and during the development and repair of the CNS/PNS. Biosynthesis of the tetrasaccharide linker sequence by addition of a xylose residue to a serine residue in the proteoglycan core protein followed by addition of two Galactose and a GlcA residue (a). Initiation of CS chain elongation occurs by addition of a GalNAc residue by chondroitin N-acetylgalactosaminyltransferase-1 or chondroitinpolymerase (b). Elongation of the CS chain occurs by sequential additions of GlcA and GalNAc to the nascent non-reducing terminus by chondroitin polymerases (c). The CS chain is sulfated by chondroitin-4 and 6-sulphotransferases, or the GlcA residue of the O-disaccharide unit is epimerized to IdoA with inversion in structure from a β-D conformation to an α-L conformation followed by a series of sulphotransferases and uronyl-2-sulphotransferase to form the CS-A, CS-B, CS-C, CS-D, CS-E and DS-iA, DS iB, CS-iC, DS-iD, and DS-iE isoforms as shown (d–f). The 4-O-sulfation pathway is most active in the adult brain (d) while various DS isoforms regulate brain development and repair processes (e). The 6-sulfation pathway (f) is most active in the juvenile brain. The DS-iO and DS-iC units have yet to be confirmed. Figure modified from Malmström et al. (2012) and Miyata and Kitagawa (2017).