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Heparan Sulfate





PROTEOGLYCANS

The major cell membrane HSPGs are the transmembrane Syndecans and the Glycosylphosphatidylinositol (GPI) anchored Glypicans . Other minor forms of membrane HSPG include betaglycan1 and the V-3 isoform of CD44 present on Keratinocytes and activated Monocytes .2

In the extracellular matrix, especially Basement Membrane s, the multi-domain Perlecan , Agrin and Collagen XVIII core proteins are the main HS-bearing species.


HS STRUCTURE AND DIFFERENCES FROM HEPARIN

Heparan sulfate is a member of the Glycosaminoglycan family of carbohydrates and is very closely related in structure to Heparin . Both consist of a variably sulfated repeating Disaccharide unit. The main disaccharide units that occur in heparan sulfate and heparin are shown below.

The most common disaccharide unit within heparan sulfate is composed of a glucuronic (GlcA) linked to N-acetyl Glucosamine (GlcNAc) typically making up around 50% of the total disaccharide units. Compare this to heparin where IdoA(2S)-GlcNS(6S) makes up 85% of heparins from beef lung and about 75% of those from porcine intestinal mucosa.
Problems arise when defining hybrid GAGs that contain both 'heparin-like' and 'HS-like' structures. It has been suggested that a GAG should qualify as heparin only if its content of N-sulfate groups largely exceeds that of N-acetyl groups and the concentration of O-sulfate groups exceeds those of N-sulfate.3

Not shown below are the rare disaccharides containing a 3-O-sulfated glucosamine (GlcNS(3S,6S) or a free Amine group (GlcNH3+). Under physiological conditions the Ester and Amide sulfate groups are deprotonated and attract positively charged counterions to form a salt. It is in this form that HS is thought to exist at the cell surface.