heparán

Heparán is a sulfated glycosaminoglycan that forms part of heparan sulfate proteoglycans (HSPGs) found on animal cell surfaces and in the extracellular matrix. It is composed of repeating disaccharide units of uronic acid (iduronic or glucuronic) and N-acetylglucosamine, with variable sulfation at N-, 2-O-, and 6-O- positions. These long chains are covalently attached to core proteins such as syndecans and glypicans, creating membrane-linked HSPGs, as well as to extracellular matrix proteoglycans like perlecan and agrin.

Biosynthesis and structure are driven by Golgi-embedded enzymes that polymerize the HS chain and introduce a diverse pattern of sulfation and epimerization. The result is a family of highly variable sulfation motifs that dictate binding to a broad range of ligands. The HS chains assemble on a common linkage region to the proteoglycan core, and after secretion can be modified further or shed from the cell surface.

Functions of heparán chains include binding and modulating interactions with growth factors (such as FGF and VEGF), chemokines, morphogens, and enzymes. Through these interactions, HS acts as a co-receptor or reservoir, influencing signaling, cell adhesion, migration, proliferation, and tissue patterning. It also participates in angiogenesis, wound healing, and inflammatory responses. Enzymes like heparanase remodel HS, and various sulfotransferases alter sulfation patterns, thereby changing ligand affinity.

Clinical relevance includes associations between HS sulfation or abundance and development, cancer progression, and fibrotic diseases. Defects in HS metabolism cause storage disorders such as mucopolysaccharidoses. Because HS can affect pathogen attachment and coagulation pathways, it is also a target of therapeutic research.