Lysosomal degradation of heparin and heparan sulfate

Heparin (HP) and heparan sulfate (HS) proteoglycans are composed of linear-sulfated glycosaminoglycan (GAG) chains of up to several hundred, alternating uronic acid and N-acetylglucosamine residues that are modified through a series of reactions to produce a complex pattern of O- and N-sulfated monosaccharide as well as epimerized uronic acid residues. The uptake pathway of HP from its site of action has not been defined. HS proteoglycans, destined for turnover, traffic through the endocytic vacuolar network to the lysosome for degradation. HS proteoglycans are routed from the cell surface via clathrin-coated vesicles that fuse with early endosomes. The degradation of HP and HS begins with endo-hydrolysis to clip the long chain polysaccharides or GAG chains to shorter oligosaccharide fragments with the action of endo-glycosidases called heparanases. The lysosomal exo-enzymes are synthesized and processed in the endoplasmic reticulum as well as the Golgi apparatus. A signal sequence is required to direct mRNA and the ribosome complex to the rough endoplasmic reticulum for the commencement of protein synthesis. © 2005