Heparan sulfate terminal α-N-acetylglucosamine residues (Terminal α-GlcNAc-HS)

Heparan sulfate terminal α-N-acetylglucosamine residues are specific carbohydrate structures found at the non-reducing ends of heparan sulfate (HS) glycosaminoglycan chains (Coutinho et al., 2012, PubMed). In healthy individuals, these residues are transient intermediates during the lysosomal degradation of HS, where they are cleaved by the enzyme α-N-acetylglucosaminidase (NAGLU) (UniProt P12259). However, in patients with Mucopolysaccharidosis type IIIB (MPS IIIB or Sanfilippo syndrome B), a genetic deficiency in NAGLU leads to the pathological accumulation of these terminal α-GlcNAc residues within lysosomes (NIH GARD). This accumulation triggers a cascade of cellular dysfunction, particularly in the central nervous system, resulting in severe neurodegeneration and cognitive decline (Sifuentes et al., 2019, PubMed). Consequently, these residues serve as both a primary driver of disease pathology and a critical biomarker for monitoring disease progression and therapeutic efficacy (Lawrence et al., 2012, Glycobiology). Therapeutic strategies, such as enzyme replacement therapy with tralesinidase alfa (BMN 250), specifically target these residues by providing the functional NAGLU enzyme to hydrolyze and clear the accumulated substrate (BioMarin Pharmaceutical Inc.).

Other names

Non-reducing end α-N-acetylglucosamine of heparan sulfateTerminal alpha-GlcNAc on heparan sulfateNAGLU substrateMPS IIIB storage product

Enzymatic hydrolysis of terminal alpha-N-acetylglucosamine residues from the non-reducing end of heparan sulfate chains by alpha-N-acetylglucosaminidase (NAGLU)