Biosynthesis of core 3 and core 4 O-GalNAc glycans. N-Acetylgalactosamine is substituted by a β1-3 N-acetylglucosamine residue to form core 3. This reaction is catalyzed by core 3 β1-3 N-acetyl-glucosaminyltransferase (C3GnT), which is active in colonic mucosa. Core 3 may be substituted with sialic acid in α2-6 linkage to N-acetylgalactosamine or with galactose in β1-4 linkage to N-acetylglucosamine. These substitutions prevent the synthesis of core 4 by core 2/4 β1-6 N-acetylglucosaminyltransferase (C2GnT-2). Red crosses mark blocked pathways. Unmodified core 3 can be branched by C2GnT-2 to form core 4. Both core 3 and core 4 O-GalNAc glycans can be extended to complex chains carrying determinants similar to those of core 1 and core 2 O-GalNAc glycans.

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