PathwayStep1070 PathwayStep1072 PathwayStep1071 PathwayStep1074 PathwayStep1073 PathwayStep1076 PathwayStep1075 PathwayStep1078 PathwayStep1077 PathwayStep1079 PathwayStep1082 PathwayStep1083 PathwayStep1080 PathwayStep1081 HS-GAG degradation Authored: Jassal, B, 2011-12-14 Edited: Jassal, B, 2011-12-14 GENE ONTOLOGYGO:0006027 Lysosomal degradation of glycoproteins is part of the cellular homeostasis of glycosylation (Winchester 2005). The steps outlined below describe the degradation of heparan sulfate/heparin. Complete degradation of glycoproteins is required to avoid build up of glycosaminoglycan fragments which can cause lysosomal storage diseases. The proteolysis of the core protein of the glycoprotein is not shown here. Pubmed15647514 Reactome Database ID Release 432024096 Reactome, http://www.reactome.org ReactomeREACT_120752 Reviewed: D'Eustachio, P, 2012-03-28 HGSNAT acetylates the terminal N-glucosamine in heparan sulfate Iduronate 2-sulfatase (IDS) hydrolyses sulfates from L-iduronate 2-sulfate units of heparan sulfate Alpha-N-acetylglucosaminidase (NAGLU) hydrolyses N-acetyl-D-glucosamine residues from heparan sulfate N-sulphoglucosamine sulphohydrolase (SGSH) hydrolyses another sulfate from the N-sulphoglucosamine residue of heparan sulfate Alpha-L-iduronidase (IDUA) hydrolyses another unsulfated alpha-L-iduronosidic linkage in heparan sulfate Alpha-N-acetylglucosaminidase (NAGLU) hydrolyses another N-acetyl-D-glucosamine residue from heparan HGSNAT acetylates another terminal N-glucosamine in heparan Beta-galactosidase (GLB1) can cleave galactose from the linker chain Beta-glucuronidase (GUSB) hydrolyses glucuronate from the linker chain HS-GAGs translocate to the lysosome for degradation Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome) N-sulphoglucosamine sulphohydrolase (SGSH) hydrolyses sulfate from the N-sulphoglucosamine residue of heparan sulfate Heparanase 2 (HPSE2) cleaves heparan sulfate from its proteoglycan (plasma membrane) Alpha-L-iduronidase (IDUA) hydrolyses the unsulfated alpha-L-iduronosidic linkage in heparan sulfate