Skip to main content
. Author manuscript; available in PMC: 2019 Mar 25.
Published in final edited form as: Matrix Biol. 2018 May 24;71-72:262–282. doi: 10.1016/j.matbio.2018.05.010

FIGURE 1. Heparan sulfate (HS) structure.

FIGURE 1.

HS biosynthesis commences by the copolymerization of alternating N-acetylated glucosamine and glucuronic acid residues on a tetrasaccharide primer (glucuronic acid (GlcA)-galactose (Gal)-galactose-xylose (Xyl)-) that is covalently bound to a serine residue in the extracellular domain of the core proteins of membrane proteoglycans and extracellular matrix proteoglycans. A, The chains undergo various modifications as shown in the top of the figure by red shading. The modifications occur in clusters of variable length (sulfated domains), which are interspersed by unmodified domains (non-sulfated domains) indicated in blue. B, HS biosynthetic enzymes convert subsets of N-acetylated glucosamine (GlcNAc) residues to N-sulfoglucosamine units (catalyzed by members of the NDST family of enzymes), epimerization of nearby glucuronic acid residues to iduronic acid (IdoA) (catalyzed by a C5 epimerase [Glce]), and additional sulfation reactions at C6 of glucosamine units, C2 of uronic acids, and C3 of N-sulfoglucosamine units (catalyzed by HS6ST, HS2ST and HS3ST isozymes). The modified domains make up binding sites for protein ligands as depicted for antithrombin and ApoE. The HS chains can be further modified once they arrive at the cell surface or in the extracellular matrix by two endosulfatases (Sulf1 and Sulf2), which remove specific sulfate groups located at C6 of glucosamine units, or by the action of extracellular heparanase (not shown).