• Heparan sulfate (HS) are expressed on all vertebrate cells as part of HS proteoglycans. Common HSPGs include perlecan, agrin, and collagen XVIII that are part of basement membranes, and cell surface syndecans and glypicans. Many growth factors, morphogens, chemokines, and cytokines are presented by the HS. Thus, HS are critical part of embryonic development and adult hemostasis.
• The first committed HS chain modification is catalyzed by one of four NDST isoforms, present in the medial and trans-Golgi. These are bifunctional enzymes that first N-deacetylase GlcNAc to generate free amino groups, followed by sulfation.
• All subsequent modification (GlcA->IdoA epimerization, O-sulfation etc.) depends on N-sulfation status except for 6-O-sulfation, which is NS-status independent. Heavily sulfated domains that are functional typically contain IdoA rather than GlcA.
• NDST1 and NDST2 showed display high deacetylase and sulfotransferase activities. NDST3 shows relatively higher deacetylase activities but low sulfotransferase activity. NDST4 has high sulfotransferase activities but low deacetylase activities.
• NDST1 & NDST2 are important enzyme mediating N-sulfation as they are widely expressed. They play a critical role in regulating cell signaling by facilitating the binding of various growth factors.
• Due to their restricted expression profile, NDST3 and NDST4 have a less penetrating impact on biological function.