Heparin and heparan sulfate—The essence of sequence

Abstract Heparin, discovered as an anticoagulant more than 100 years ago, is composed of the same structural units as heparan sulfate, and their biosynthesis in the Golgi compartment is carried out by the same families of enzymes. However, while heparin is restricted to mast cells, heparan sulfate is widely distributed and is found at the cell surface of most, if not all, cells in the body and also in basement membranes and the extracellular matrix surrounding cells. Compared to the highly sulfated heparin, heparan sulfate has a complex and variable structure that yet appears regulated in tissue‐specific fashion. Interactions of proteins with heparan sulfate may be controlled through subtle structural changes of binding saccharide domains, resulting in modulated functional response. Unpredicted effects of enzyme overexpression on heparan sulfate structure point to key roles for interacting enzyme networks—the "GAGosome"—in regulation of heparan sulfate biosynthesis.