Skip to content
DraconiticBiochemistryBiomolecules · Catabolism · Biosynthesis · MetabolismMap
Data
100%

Loading the map…

Glycosaminoglycan metabolism

Biosynthesis and turnover of sulfated and non-sulfated glycosaminoglycan chains across secretory and lysosomal compartments. 98 reactions, from Reactome R-HSA-1630316.

  1. ARSB hydrolyses DSH2O + ChEBI:63519 chain → SO4(2-) + ChEBI:63517 chain
  2. GALNS oligomer hydrolyses sulfate from Gal6S in keratan sulfateH2O + Gal(S)-GlcNAc(S)-Gal-GlcNAc(S)-Gal → SO4(2-) + Gal-GlcNAc(S)-Gal-GlcNAc(S)-Gal
  3. GLB1 hydrolyses a glycosaminoglycanH2O + Gal-GlcNAc(S)-Gal-GlcNAc(S)-Gal → Gal + GlcNAc(S)-Gal-GlcNAc(S)-Gal
  4. GNS:Ca2+ cleaves sulfate from GlcNAc-6-sulfate units of keratan sulfateH2O + GlcNAc(S)-Gal-GlcNAc(S)-Gal → SO4(2-) + GlcNAc-Gal-GlcNAc(S)-Gal
  5. HEXA cleaves the terminal GlcNAc from keratan sulfateH2O + GlcNAc-Gal-GlcNAc(S)-Gal → Gal-GlcNAc(S)-Gal + GlcNAc
  6. Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)H2O + HS/HPIN-PGs → IdoA-GlcN6S-IdoA2S-GlcN3S- group + GlcA-Gal-Gal-Xyl-HS proteins
  7. IDS hydrolyses Heparan sulfate chain(5)H2O + IdoA2S-GlcNS3S- group → SO4(2-) + IdoA-GlcNS3S- group
  8. HGSNAT oligomer acetylates Heparan sulfate chain(3)Ac-CoA + GlcN-IdoA2S-GlcNS3S- group → CoA-SH + GlcNAc-IdoA2S-GlcNS3S- group + H+
  9. Heparanase 2 (HPSE2) binds heparan sulfate proteoglycansHS/HPIN-PGs + HPSE2(1-592) → HPSE2:HS/HPIN-PGs
  10. SGSH hydrolyses Heparan sulfate chain(2)2 H2O + GlcNS6S-IdoAS2-GlcNS3S- group → 2 SO4(2-) + GlcN-IdoA2S-GlcNS3S- group
  11. IDUA cleaves iduronate from HS chainH2O + IdoA-GlcN6S-IdoA2S-GlcN3S- group → aldehydo-L-iduronic acid + GlcNS6S-IdoAS2-GlcNS3S- group
  12. NAGLU hydrolyses Heparan sulfate chain(4)GlcNAc-IdoA2S-GlcNS3S- group + H2O → GlcNAc + IdoA2S-GlcNS3S- group
  13. GUSB tetramer hydrolyses CS/HS precursorCS/HS precursor + H2O → GlcA + linker chain(2)
  14. PAPSS1,2 transfer PO4(2-) group from ATP to APS to form PAPSATP + APS → ADP + PAPS + H+
  15. PAPSS1,2 transfer SO4(2-) group to ATP to form APSATP + SO4(2-) + H+ → APS + PPi
  16. DS is cleaved from its proteoglycanH2O + D2,4,4(S)3-PGs → CS/DS core proteins + ChEBI:63519 chain
  17. IDS hydrolyses dermatan sulfate (Chebi:63517 chain)H2O + ChEBI:63517 chain → SO4(2-) + ChEBI:63516 chain
  18. IDUA hydrolyses the unsulfated alpha-L-iduronosidic link in DSH2O + IdoA-GalNAc(4S)-GlcA-Gal-Gal-Xyl → aldehydo-L-iduronic acid + CHEBI:63868 chain
  19. ARSB hydrolyses C4S/C6S chainsH2O + C4S/C6S chains → SO4(2-) + Chondroitin chain
  20. HYAL1-4 hydrolyze chondroitin chainsH2O + Chondroitin chains → CS/HS precursor
  21. Unknown endo-β-galactosidase cleaves keratan chainH2O + KSPG(2) → KS core proteins + Gal(S)-GlcNAc(S)-Gal-GlcNAc(S)-Gal
  22. XYLTs transfer Xyl to core proteinUDP-Xyl + GAG core proteins → UDP + xylosyl-core proteins + H+
  23. B3GAT dimers transfer GlcA to tetrasaccharide linkerGal-Gal-Xyl-proteins + UDP-GlcA → UDP + GlcA-Gal-Gal-Xyl-proteins + H+
  24. B3GALT6 transfers Gal to the tetrasaccharide linkerGal-Xyl-proteins + UDP-Gal → UDP + H+ + Gal-Gal-Xyl-proteins
  25. B4GALT7 transfers Gal group to xylosyl-unit of the tetrasaccharide linkerxylosyl-core proteins + UDP-Gal → Gal-Xyl-proteins + UDP + H+
  26. CSGALNACTs transfer GalNAc to CS linker glycanUDP-GalNAc + GlcA-Gal-Gal-Xyl-CS proteins → UDP + chondroitin(1)-core proteins + H+
  27. CHST11,12,13,9 transfer sulfate to (4-)GalNAcchondroitin(3)-core proteins + PAPS → C4S-PG + PAP + H+
  28. Chondroitin polymerase complex transfers GalNAc to CS chainchondroitin(2)-core proteins + UDP-GalNAc → UDP + chondroitin(3)-core proteins + H+
  29. Chondroitin polymerase complex transfers GlcA to CS chainUDP-GlcA + chondroitin(1)-core proteins → UDP + chondroitin(2)-core proteins + H+
  30. CHST15 transfers sulfate to (6-)GalNAc-4-sulfateC4S-PG + PAPS → PAP + H+ + CSE-PG
  31. CHST3,7 transfer SO4(2-) to position 6 of GalNAc on chondroitin chainschondroitin(3)-core proteins + PAPS → PAP + C6S-PG + H+
  32. DSE converts GlcA to IdoADSE,DSEL substrates → DSE,DSEL products
  33. DSPG and CSPG translocate to the lysosome for degradationCSPGs,DSPGs → CSPGs,DSPGs
  34. Dermatan sulfate can be further sulfated on position 2 of iduronateD4S-PGs + PAPS → PAP + D2,4(S)2-PG + H+
  35. CHST14 transfers SO4(2-) to GalNAc in dermatan or DSCHST14 substrates + PAPS → PAP + CHST14 products + H+
  36. DSPGs are secretedDSPGs → DSPGs
  37. EXT1:EXT2 transfers GlcNAc to the heparan chainUDP-GlcNAc + Heparan(1)-PGs → UDP + Heparan(2)-PGs + H+
  38. EXT1:EXT2 transfers GlcA to heparanUDP-GlcA + Heparan-PGs → UDP + Heparan(1)-PGs + H+
  39. NDST1-4 can sulfate a glucosamine residue in heparan to form heparan sulfate (HS)2 PAPS + Heparan(4)-PGs → 2 PAP + HS(1)-PGs + H+
  40. NDST1-4 N-deacetylates GlcNAc residues in heparanH2O + Heparan(3)-PGs → CH3COO- + Heparan(4)-PGs
  41. CSPG is secretedCSPGs → CSPGs
  42. HS-GAGs translocate to the lysosome for degradationHS/HPIN-PGs → HS/HPIN-PGs
  43. GLCE epimerises GlcA to IdoAHS(1)-PGs → HS(2)-PGs
  44. Some HSPGs are secreted to the plasma membraneHSPGs → HSPGs
  45. B4GALTs transfer Gal to the N-glycan precursorUDP-Gal + N-glycan-protein → UDP + Gal-glycan-protein + H+
  46. B3GNT1,2,3,4,7 add GlcNAc to form Keratan-PGUDP-GlcNAc + Gal-glycan-protein → UDP + Keratan(1)-PG + H+
  47. CHST1 transfers sulfate to Gal on keratan chainKSPG(1) + PAPS → KSPG(2) + PAP
  48. KSPG is secreted from the cellKSPG(2) → KSPG(2)
  49. CHST2,3,5,6 transfer sulfate to GlcNAc on keratan chainKeratan(4)-PG + PAPS → PAP + KSPG(1) + H+
  50. Extracellular KSPG translocates to the lysosome for degradationKSPG(2) → KSPG(2)
  51. B4GALTs transfer Gal to the keratan chainKeratan(1)-PG + UDP-Gal → UDP + Keratan(2)-PG + H+
  52. ST3GAL1-4,6 optionally cap keratan chainKeratan(3)-PG + CMP-Neu5Ac → CMP + Keratan(4)-PG + H+
  53. B4GALTs transfer Gal to a branch of keratanKeratan(2)-PG + UDP-Gal → UDP + Keratan(3)-PG + H+
  54. CS is cleaved from its proteoglycanH2O + CSPGs → CS/DS core proteins + C4S/C6S chains
  55. GLCE epimerises more GlcA to IdoA as sulfate content risesHS(4)-PGs → HS(5)-PGs
  56. HS3ST1 sulfates GlcN at C3 in heparan sulfateHS(3)-PGs + PAPS → PAP + HS(4)-PGs + H+
  57. EXT1:EXT2 transfers GlcA to heparanUDP-GlcA + Heparan(2)-PGs → UDP + Heparan(3)-PGs + H+
  58. HS6STs sulfate GlcN at C6 in heparan sulfate/heparinHS(5)-PGs + PAPS → PAP + HS/HPIN-PGs + H+
  59. HS2ST1 trimer sulfates IdoA at C2 in heparan sulfateHS(2)-PGs + PAPS → PAP + HS(3)-PGs + H+
  60. HS3ST2-6 sulfate GlcN at C3 in heparan sulfateHS(3)-PGs + PAPS → PAP + HS(4)-PGs + H+
  61. IDUA hydrolyses Heparan sulfate chain(6)H2O + IdoA-GlcNS3S- group → aldehydo-L-iduronic acid + GlcNS3S- group
  62. NAGLU hydrolyses heparan chain(2)H2O + GlcNAc- group → GlcNAc + -R
  63. SGSH hydrolyses Heparan sulfate chain(7)2 H2O + GlcNS3S- group → 2 SO4(2-) + GlcN- group
  64. GLB1 hydrolyses linker chain(2)2 H2O + linker chain(2) → 2 Gal + D-xylose
  65. HGSNAT oligomer acetylates Heparan chain(1)Ac-CoA + GlcN- group → CoA-SH + GlcNAc- group + H+
  66. HEXA cleaves the terminal GalNAc from DSH2O + ChEBI:63516 chain → GalNAc + IdoA-GalNAc(4S)-GlcA-Gal-Gal-Xyl
  67. Growing HA is extruded from the cell by ABCC5HA polymer → HA
  68. HAS1,2,3 mediate the polymerization and export of HAUDP-GlcA + UDP-GlcNAc → 2 H+ + 2 UDP + HA
  69. HYAL1 hydrolyses (HA)50(HA)50 + 25 H2O → 25 (HA)2
  70. HA:HAR:HYAL2 binds to SLC9A1:p-CHP:Ca2+HA:HAR:HYAL2 + SLC9A1:p-CHP:Ca2+ → HA:HAR:HYAL2:SLC9A1:pCHP:Ca2+
  71. HYAL2 hydrolyses HA into 20kDa fragmentsHA:HAR:HYAL2 + H2O → (HA)50 + HAR:HYAL2
  72. 20kDa HA fragments are translocated to lysosomes(HA)50 → (HA)50
  73. Receptor-mediated uptake of HAHA + HYAL2 + HARs → HA:HAR:HYAL2
  74. HEXA cleaves the terminal GlcNAc from small HA fragmentsH2O + GlcNAc-GlcA-GlcNAc → GlcNAc + GlcA-β1,3-GlcNAc
  75. GUSB tetramer hydrolyzes GlcA-β1,3-GlcNAcH2O + GlcA-β1,3-GlcNAc → GlcA + GlcNAc
  76. GUSB tetramer hydrolyses (HA)2H2O + (HA)2 → GlcA + GlcNAc-GlcA-GlcNAc
  77. SLC17A5 exports GlcA from the lysosome to the cytosolGlcA + H+ → GlcA + H+
  78. SLC26A1,2 cotransport SO4(2-), anion from extracellular region to cytosolSO4(2-) + SLC26A1,2 cargo → SO4(2-) + SLC26A1,2 cargo
  79. CEMIP hydrolyzes HAHA → HA + (HA)50
  80. SLC35B2,3 exchange cytosolic PAPS with Golgi PAPPAPS + PAP → PAPS + PAP
  81. SLC35D2 exchanges UDP-GlcNAc for UMPUMP + UDP-GlcNAc → UMP + UDP-GlcNAc
  82. UXS1 tetramer decarboxylates UDP-glucuronate to UDP-xyloseUDP-GlcA + H+ → UDP-Xyl + CO2
  83. CSGALNACTs transfer GalNAc to CS chainchondroitin(2)-core proteins + UDP-GalNAc → UDP + chondroitin(3)-core proteins + H+
  84. HEXB cleaves the terminal GalNAc from DSH2O + ChEBI:63516 chain → GalNAc + IdoA-GalNAc(4S)-GlcA-Gal-Gal-Xyl
  85. HEXB cleaves the terminal GlcNAc from small HA fragmentsH2O + GlcNAc-GlcA-GlcNAc → GlcNAc + GlcA-β1,3-GlcNAc
  86. HEXB cleaves the terminal GlcNAc from keratan sulfateH2O + GlcNAc-Gal-GlcNAc(S)-Gal → Gal-GlcNAc(S)-Gal + GlcNAc
  87. CTSL1 cleaves proHPSEproHPSE → HPSE dimer
  88. proHPSE binds SDC1HS(6)-SDC1 + proHPSE → proHPSE:SDC1
  89. proHPSE:SDC1 is delivered to lysosomesproHPSE:SDC1 → proHPSE:SDC1
  90. PXYLP1 dephosphorylates Xyl moietyGlcA-Gal-Gal-XylP-proteins + H2O → GlcA-Gal-Gal-Xyl-proteins + Pi
  91. FAM20B phosphorylates Xyl moietyGlcA-Gal-Gal-Xyl-proteins + ATP → GlcA-Gal-Gal-XylP-proteins + ADP + H+
  92. SPAM1 randomly cleaves HAHA → HA + (HA)50
  93. proHPSE dissociates from HS(6)-SDC1proHPSE:SDC1 → proHPSE + HS(6)-SDC1
  94. ROS/RNS degrade HAROS,RNS + HA → HA + (HA)50
  95. UST transfers sulfate to (2-)GlcA-GalNAc-6-sulfateC6S-PG + PAPS → C2S6S-PG + PAP + H+
  96. CHST15 transfers sulfate to (6-)GalNAc-4-sulfatePAPS + D4S-PGs → PAP + H+ + D4,6S-PGs
  97. SLC26A11 imports SO4(2-) and H+ into cytosolH+ + SO4(2-) → H+ + SO4(2-)
  98. EXTL3 dimer transfers GlcNAc to the GAG linkerUDP-GlcNAc + GlcA-Gal-Gal-Xyl-HS proteins → UDP + Heparan-PGs + H+