Heparan sulfate glycosaminoglycan with terminal N-acetyl-D-glucosamine residues (HS-GlcNAc)

Heparan sulfate glycosaminoglycans (HS GAGs) with terminal N-acetyl-D-glucosamine (GlcNAc) residues are specialized carbohydrate structures that play a critical role in lysosomal metabolism and cellular signaling (Essentials of Glycobiology, 3rd edition, 2017). In the normal physiological state, these terminal residues are specifically cleaved by the enzyme alpha-N-acetylglucosaminidase (NAGLU) during the stepwise degradation of heparan sulfate (PubMed: 29102128). A genetic deficiency in this enzyme results in Mucopolysaccharidosis type IIIB (MPS IIIB), a lysosomal storage disorder characterized by the massive accumulation of these GlcNAc-terminated HS chains (NIH GARD, 2023). This accumulation is particularly toxic to the central nervous system, leading to severe neurodegeneration, cognitive decline, and behavioral issues (PubMed: 31141830). Therapeutic interventions, such as enzyme replacement therapy (e.g., tralesinidase alfa) and gene therapy, aim to provide functional NAGLU to hydrolyze these terminal residues and clear the stored substrate (ClinicalTrials.gov: NCT03300453). Monitoring the levels of these specific HS fragments in biological fluids serves as a vital biomarker for assessing disease severity and the biochemical efficacy of emerging treatments (PubMed: 30685585).

Other names

Sanfilippo B substratealpha-GlcNAc-terminated heparan sulfateN-acetyl-D-glucosamine-capped heparan sulfateHS-GlcNAc

Enzymatic hydrolysis of terminal alpha-N-acetyl-D-glucosamine residues by recombinant or gene-delivered alpha-N-acetylglucosaminidase (NAGLU) (PubMed: 29102128).