Heparan

Heparan refers to a family of sulfated, linear polysaccharides that includes heparan sulfate and its closely related glycosaminoglycan, heparin. In animals, these long chains are typically covalently attached to core proteins to form heparan sulfate proteoglycans (HSPGs), which are widespread on cell surfaces and within the extracellular matrix.

The repeating disaccharide units of heparan chains consist of uronic acid (iduronic or glucuronic) linked to glucosamine. The chains are variably sulfated at multiple positions, including N-sulfation of glucosamine, 2-O sulfation of uronic acid, and 6-O sulfation of glucosamine, with occasional 3-O sulfation. Biosynthesis occurs in the Golgi apparatus through a sequence of polymerization and extensive post-synthetic modification by sulfotransferases and epimerases, producing domains with distinct binding properties. Heparin is a more highly sulfated member, primarily produced by mast cells and used pharmacologically as an anticoagulant.

Functions of heparan are diverse. Through their proteoglycan forms, heparan sulfates interact with a wide range of proteins, including growth factors, chemokines, morphogens, enzymes, and receptors. They can act as co-receptors or reservoirs that modulate signaling pathways (such as FGF, Wnt, and Hedgehog), influence cell adhesion and migration, and contribute to the organization of the extracellular matrix and basement membranes. They also participate in endocytosis, tissue filtration in the kidney, and, in certain contexts, anticoagulation.

Clinical and research relevance is broad. Altered sulfation patterns and HSPG function are linked to developmental disorders, cancer progression, inflammation, and viral attachment for several pathogens. Heparin remains a clinically important anticoagulant.