Degradation of Glycosaminoglycan

GAG are degraded in lysosomes, which contain hydrolytic enzymes that are most active at a pH of ~5. Therefore, as a group, these enzymes are called acid hydrolases. [Note: The low pH optimum is a protective mechanism that prevents the enzymes from destroying the cell should leakage occur into the cytosol where the pH is neutral.] The half-lives of GAG vary from minutes to months and are influenced by the type of GAG and its location in the body.
A. GAG phagocytosis
Because GAG are extracellular or cell-surface compounds, they must first be engulfed by invagination of the cell membrane (phagocytosis), forming a vesicle inside of which are the GAG to be degraded. This vesicle then fuses with a lysosome, forming a single digestive vesicle in which the GAG are efficiently degraded .
B. Lysosomal degradation
The lysosomal degradation of GAG requires a large number of acid hydrolases for complete digestion. First, the polysaccharide chains are cleaved by endoglycosidases, producing oligosaccharides. Further degradation of the oligosaccharides occurs sequentially from the nonreducing end  of each chain, the last group (sulfate or sugar)
added during synthesis being the first group removed (by sulfatases or exoglycosidases). Examples of some of these enzymes and the bonds they hydrolyze are shown in Figure 1. [Note: Endo- and exoglycosidases are also involved in the lysosomal degradation of glycoproteins and glycolipids . Deficiencies in these enzymes result in the accumulation of partially degraded carbohydrates, causing tissue damage.]

Figure 1: Degradation of the glycosaminoglycan heparan sulfate by lysosomal enzymes, indicating sites of enzyme deficiencies in some representative mucopolysaccharidoses (MPS). [Note: Deficiencies in galactosamine 6-sulfatase and β-galactosidase that degrade keratan sulfate result in Morquio syndrome (MPS IV), A and B, respectively. Deficiencies in arylsulfatase B that degrades dermatan sulfate result in Maroteaux-Lamy syndrome (MPS VI).] GlcUA and IdUA = glucuronic and iduronic acids; GalNAc = N-acetylgalactosamine; GlcNAc = N-acetylglucosamine; GlcN = glucosamine; S = sulfate.
Multiple sulfatase deficiency (Austin disease) is a rare lysosomal storage disease in which all sulfatases are nonfunctional because of a defect in the formation of formylglycine, an amino acid derivative required at the active site for enzymic activity to occur.