Glycosaminoglycan substrates of alpha-L-iduronidase (GAGs) (GAGs)

Glycosaminoglycan (GAG) substrates of alpha-L-iduronidase, specifically dermatan sulfate and heparan sulfate, are long, unbranched polysaccharides consisting of repeating disaccharide units. These molecules are critical components of the extracellular matrix and play vital roles in cell signaling, growth factor sequestration, and tissue architecture (UniProt P35475). In the lysosome, the enzyme alpha-L-iduronidase (IDUA) is responsible for the degradation of these GAGs by hydrolyzing terminal alpha-L-iduronic acid residues (NCBI Gene ID: 3425). A deficiency in IDUA activity leads to Mucopolysaccharidosis type I (MPS I), a lysosomal storage disorder characterized by the pathological accumulation of dermatan and heparan sulfate in various tissues, leading to progressive organ damage, skeletal abnormalities, and neurological decline (PubMed: 25385331). Therapeutic strategies targeting these substrates include enzyme replacement therapy (ERT) with recombinant human IDUA (e.g., laronidase), which facilitates their degradation, and substrate reduction therapy (SRT), which aims to decrease their synthesis to manageable levels (PubMed: 30111439). Monitoring urinary and systemic GAG levels serves as a primary biomarker for disease progression and treatment efficacy in affected patients.

Other names

Dermatan sulfateHeparan sulfateMucopolysaccharidesAcid mucopolysaccharides

Enzymatic hydrolysis of terminal alpha-L-iduronic acid residues; inhibition of glycosaminoglycan synthesis