Reaction: HGSNAT oligomer acetylates Heparan sulfate chain(3)
- in pathway: HS-GAG degradation
Heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT) acetylates the non-reducing terminal alpha-glucosamine residue of heparan sulfate. This is a critical reaction for the degradation of heparan sulfate because there is no enzyme that can act on the unacetylated glucosamine molecule. The mechanism by which HGSNAT uses cytosolic acetyl-CoA to transfer the acetyl group to the lysosomal luminal substrate is unknown (Fan et al. 2006). A catalytically inactive 77kDa precursor is transported to the lysosome and is cleaved into a 29kDa N-terminal alpha-chain and a 48kDa C-terminal beta-chain, which are assembled into active 440kDa oligomers in the lysosomal membrane (Durand et al. 2010). Defects in HGSNAT cause mucopolysaccharidosis type IIIC (MPSIIIC, MIM:252930), also called Sanfilippo C syndrome (Fan et al. 2006, Hrebicek et al. 2006).
Reaction - small molecule participants:
Heparan sulfate chain(4) [lysosomal lumen]
CoA-SH [cytosol]
Heparan sulfate chain(3) [lysosomal lumen]
Ac-CoA [cytosol]
Reactome.org reaction link: R-HSA-1678660
======
Reaction input - small molecules:
alpha-D-GlcN-(1->4)-beta-D-IdoA2S-(1->4)-alpha-D-GlcNS3S-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl-yl group
acetyl-CoA(4-)
Reaction output - small molecules:
alpha-D-GlcNAc-(1->4)-beta-D-IdoA2S-(1->4)-alpha-D-GlcNS3S-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl-yl group
coenzyme A(4-)
Reactome.org link: R-HSA-1678660