Glycosaminoglycan substrates of iduronate-2-sulfatase (GAG substrates)

Glycosaminoglycan substrates of iduronate-2-sulfatase, primarily heparan sulfate and dermatan sulfate, are complex linear polysaccharides that serve as essential components of the extracellular matrix and cell surfaces (UniProt P22735). These molecules are involved in critical biological processes, including tissue structural integrity and the modulation of growth factor signaling (PubMed: 21310426). In healthy cells, the lysosomal enzyme iduronate-2-sulfatase (IDS) is responsible for the stepwise degradation of these glycosaminoglycans by removing the 2-sulfate group from L-iduronate residues. A deficiency in this enzymatic activity leads to the progressive accumulation of these substrates within lysosomes, a hallmark of the lysosomal storage disorder known as Hunter syndrome or Mucopolysaccharidosis type II (NIH: GARD). This accumulation results in widespread cellular damage and multi-organ dysfunction, affecting the skeletal, respiratory, and central nervous systems. Therapeutic strategies, such as enzyme replacement therapy (ERT) with idursulfase, aim to reduce the burden of these accumulated substrates by providing a functional version of the missing enzyme to facilitate their breakdown (FDA: Elaprase Label).

Other names

Heparan sulfateDermatan sulfateMucopolysaccharidesL-iduronate 2-sulfate containing glycosaminoglycansChondroitin sulfate B

Hydrolysis of the 2-sulfate group from C2 of L-iduronate residues within the glycosaminoglycan chain by exogenous or endogenous iduronate-2-sulfatase.