ABCC5
MRP5
UniProt:O15440 ABCC5
CHST1
UniProt:O43916 CHST1
GLCE
KIAA0836
UniProt:O94923 GLCE
GNS
UniProt:P15586 GNS
IDUA
UniProt:P35475 IDUA
HSS
SGSH
UniProt:P51688 SGSH
NAGLU
UFHSD1
UniProt:P54802 NAGLU
HYAL1
LUCA1
UniProt:Q12794 HYAL1
HFRC
SLC35D2
UGTREL8
UniProt:Q76EJ3 SLC35D2
BRAG
CHST15
GALNAC4S6ST
KIAA0598
UniProt:Q7LFX5 CHST15
HS2ST
HS2ST1
KIAA0448
UniProt:Q7LGA3 HS2ST1
CHST14
D4ST1
UniProt:Q8NCH0 CHST14
HPA2
HPSE2
UniProt:Q8WWQ2 HPSE2
B3GALT6
UniProt:Q96L58 B3GALT6
B4GALT7
UniProt:Q9UBV7 B4GALT7
XGALT1
DSE
SART2
UniProt:Q9UL01 DSE
DS2ST
UST
UniProt:Q9Y2C2 UST
SLC26A1,2 transport extracellular SO4(2-) to cytosol
SLC35B2,3 transport cytosolic PAPS to Golgi lumen
SLC35D2 exchanges UDP-sugars for UMP
HAS1,2,3 mediate the polymerisation of HA
Growing HA is extruded from the cell by ABCC5
Receptor-mediated uptake of HA
HYAL2 interacts with NHE1 to create an acidic environment
Hyaluronidase 2 (HYAL2) hydrolyses HA into 20kDa fragments
20kDa HA fragments are translocated to lysosomes
Hyaluronidase 1 (HYAL1) hydrolyses HA from 20kDa to 800Da fragments
Beta-glucuronidase (GUSB) hydrolyses glucuronate from HA tetrasaccharides
Beta-hexosaminidase A (BHEXA) cleaves the terminal GalNAc from small HA fragments
Beta-glucuronidase (GUSB) hydrolyses glucuronate from the HA disaccharides
The single sugars GlcA and GlcNAc translocate from the lysosome to the cytosol
ATP + sulfate => adenylyl sulfate (APS) + pyrophosphate
Activation of inorganic sulfate forms APS
PAPSS1,2 transfer PO4(2-) group from ATP to form APS
APS reacts with another ATP molecule to form PAPS
PAPSS1,2 transfer PO4(2-) group from ATP to APS to form PAPS
adenylyl sulfate (APS) + ATP => PAPS + ADP
B4GALTs add galactose to the N-glycan precursor
B3GNT1,2,3,4,7 add GlcNAc to form Keratan-PG
B4GALTs add another galactose to the chain
B4GALTs can add galactose to a branch of keratan
The keratan chain can be capped by N-acetylneuraminic acid
Sulfation of GlcNAc residues on Keratan-PG forms KSPG
Further sulfation on galactose residues produces KSPG
KSPG is secreted from the cell
Extracellular KSPG translocates to the lysosome for degradation
Keratan sulfate is cleaved from its proteoglycan by an unknown galactosidase
N-acetylgalactosamine-6-sulfatase (GALNS) hydrolyses the sulfate groups of galactose 6-sulfate units of keratan sulfate
Beta-galactosidase (GLB1) can cleave galactose from a glycosaminoglycan
N-acetylglucosamine 6-sulfatase (GNS) hydrolyses 6-sulfate groups of the N-acetyl-D-glucosamine 6-sulfate units of keratan sulfate
Beta-hexosaminidase A (BHEXA) cleaves the terminal GalNAc from keratan sulfate
GXYLTs transfer Xyl to core protein
Xylose is transferred to a serine residue on the core protein
B4GALT7 transfers Gal group to tetrasaccharide linker
Galactose is the second sugar added in the tetrasaccharide linker
A second galactose is added in the tetrasaccharide linker
B3GALT6 transfers Gal to the tetrasaccharide linker
A glucuronate moiety is the fourth addition to the tetrasaccharide linker
B3GATs transfer GlcA to tetrasaccharide linker
The addition of GlcNAc to the terminal glucuronate residue creates heparan
Glucuronate is added to the heparan chain
Another GlcNAc addition extends the heparan chain
Another GlcA addition extends the heparan chain
NDST1-4 N-deacetylates GlcNAc residues in heparan
NDST1-4 can sulfate a glucosamine residue in heparan to form heparan sulfate (HS)
GLCE epimerises GlcA to IdoA
HS2ST1 sulfates IdoA at C2 in heparan sulfate
HS3STs sulfate GlcN at C3 in heparan sulfate
HS3ST1 sulfates GlcN at C3 in heparan sulfate
GLCE epimerises more GlcA to IdoA as sulfate content rises
HS6STs sulfate GlcN at C6 in heparan sulfate/heparin
Some HSPGs are secreted to the plasma membrane
HS-GAGs translocate to the lysosome for degradation
Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)
Heparanase 2 (HPSE2) cleaves heparan sulfate from its proteoglycan (plasma membrane)
Alpha-L-iduronidase (IDUA) hydrolyses the unsulfated alpha-L-iduronosidic linkage in heparan sulfate
N-sulphoglucosamine sulphohydrolase (SGSH) hydrolyses sulfate from the N-sulphoglucosamine residue of heparan sulfate
HGSNAT acetylates the terminal N-glucosamine in heparan sulfate
Alpha-N-acetylglucosaminidase (NAGLU) hydrolyses N-acetyl-D-glucosamine residues from heparan sulfate
Iduronate 2-sulfatase (IDS) hydrolyses sulfates from L-iduronate 2-sulfate units of heparan sulfate
Alpha-L-iduronidase (IDUA) hydrolyses another unsulfated alpha-L-iduronosidic linkage in heparan sulfate
N-sulphoglucosamine sulphohydrolase (SGSH) hydrolyses another sulfate from the N-sulphoglucosamine residue of heparan sulfate
HGSNAT acetylates another terminal N-glucosamine in heparan
Alpha-N-acetylglucosaminidase (NAGLU) hydrolyses another N-acetyl-D-glucosamine residue from heparan
Beta-glucuronidase (GUSB) hydrolyses glucuronate from the linker chain
Beta-galactosidase (GLB1) can cleave galactose from the linker chain
The addition of GalNAc to the terminal glucuronate residue forms chondroitin
A glucuronate moiety is added to chondroitin
GalNAc is added to chondroitin
Chondroitin can be sulfated on position 4 of GalNAc by CHST9, 11, 12 and 13
Chondroitin 4-sulfate (C4S) can be further sulfated on position 6 by CHST15
Chondroitin can be sulfated on position 6 of GalNAc by CHST3,7
CSPG is secreted
Dermatan-sulfate epimerase (DSE) converts chondroitin sulfate (CS) to dermatan sulfate (DS)
Dermatan sulfate can be further sulfated on position 2 of iduronate
CHST14 transfers SO4(2-) to DS
GalNAc is sulfated on position 4 once dermatan sulfate is formed
DSPGs are secreted
DSPG and CSPG translocate to the lysosome for degradation
DS is cleaved from its proteoglycan
CS is cleaved from its proteoglycan
Arylsulfatase B (ARSB) hydrolyses sulfate groups from GalNAc 4-sulfate units of DS
Iduronate 2-sulfatase (IDS) hydrolyses sulfates from L-iduronate 2-sulfate units of dermatan sulfate
Beta-hexosaminidase A (BHEXA) cleaves the terminal GalNAc from DS
Alpha-L-iduronidase (IDUA) hydrolyses the unsulfated alpha-L-iduronosidic linkage in DS
Arylsulfatase B (ARSB) hydrolyses sulfate groups from GalNAc 4-sulfate units of CS
Hyaluronidase 1 (HYAL1) hydrolyses 1-4 linkages between GalNAc and D-glucuronate residues in CS.
Defective HYAL1 does not hydrolyse 1-4-linkages between GlcNAc and GlcA
Glycosaminoglycan metabolism
Hyaluronan metabolism
Hyaluronan biosynthesis and export
Hyaluronan uptake and degradation
Transport and synthesis of PAPS
Keratan sulfate/keratin metabolism
Keratan sulfate biosynthesis
Keratan sulfate degradation
Heparan sulfate/heparin (HS-GAG) metabolism
A tetrasaccharide linker sequence is required for GAG synthesis
HS-GAG biosynthesis
HS-GAG degradation
Chondroitin sulfate/dermatan sulfate metabolism
Chondroitin sulfate biosynthesis
Dermatan sulfate biosynthesis
CS/DS degradation
MPS IX - Natowicz syndrome