Glycosaminoglycans (Dermatan sulfate and Heparan sulfate) (GAGs)

The lysosomal substrates of iduronate-2-sulfatase (IDS) are primarily the glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate (UniProt P22304). These complex linear polysaccharides are essential components of the extracellular matrix and cell membranes, but they require constant turnover through lysosomal degradation (Neufeld & Muenzer, 2001). The enzyme IDS is responsible for the hydrolysis of the C2-sulfate ester group from 2-sulfated L-iduronate residues within these GAG chains. A deficiency in IDS activity, caused by mutations in the IDS gene, leads to Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome (PubMed: 11897817). In this condition, the failure to degrade these substrates results in their progressive accumulation within lysosomes, leading to widespread cellular damage and multi-systemic clinical manifestations, including coarse facial features, organomegaly, and neurological decline. Therapeutic interventions such as enzyme replacement therapy (ERT) utilize recombinant IDS (e.g., idursulfase) to facilitate the breakdown of these accumulated substrates (Wraith et al., 2008). Monitoring GAG levels in urine and other biofluids is a standard practice for diagnosing the disease and assessing the efficacy of treatment (Giugliani et al., 2021).

Other names

Dermatan sulfateHeparan sulfateMucopolysaccharidesGlycosaminoglycansGAGsChondroitin sulfate BHeparitin sulfate

Enzymatic hydrolysis of 2-sulfate groups from L-iduronate residues to facilitate lysosomal degradation of glycosaminoglycans.