Glycosaminoglycan synthesis in fibroblasts (Homo sapiens)

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Description

Glycosaminoglycans (GAGs) are key components of the extracellular matrix secreted by fibroblasts. This pathway shows the metabolic reactions necessary to synthesize three types of GAGs, namely chondroitin sulfate, dermatan sulfate and heparan sulfate. The synthesis takes place in the Golgi apparatus and begins with UDP-α-D-xylose. After this molecule is converted to 3-β-D-glucosyluronate-3-β-D-galactosyl-4-β-D-galactosyl-O-β-D-xylosyl-[protein] via three metabolic reactions, the pathway separates into two branches. One of them leads to the synthesis of chondroitin sulfate and dermatan (di)sulfate, while the other ends with heparan mono-, bi- or trisulfate. Some of the reactions are catalyzed by unknown enzymes that should be researched in the future.

This pathway was created based on the information from the pathways found in MetaCyc and HumanCyc databases (see Bibliography). As some of the metabolites do not have identifiers in databases supported by PathVisio (such as ChEBI or KEGG), their MetaNetX IDs were added in the comments.

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Bibliography

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  1. Caspi R; ''Pathway: glycosaminoglycan-protein linkage region biosynthesis''; https://metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6557, 2010
  2. Casale J, Crane JS; ''Biochemistry, Glycosaminoglycans''; https://www.ncbi.nlm.nih.gov/books/NBK544295/#:~:text=The%20process%20of%20GAG%20biosynthesis,and%20UDP%2DN%2Dacetylgalactosamine., 2023
  3. Basu A, Patel NG, Nicholson ED, Weiss RJ; ''Spatiotemporal diversity and regulation of glycosaminoglycans in cell homeostasis and human disease.''; Am J Physiol Cell Physiol, 2022 PubMed Europe PMC Scholia
  4. Huang YF, Mizumoto S, Fujita M; ''Novel Insight Into Glycosaminoglycan Biosynthesis Based on Gene Expression Profiles.''; Front Cell Dev Biol, 2021 PubMed Europe PMC Scholia
  5. Caspi R; ''Pathway: heparan sulfate biosynthesis''; https://metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6558&detail-level=2, 2010
  6. Caspi R, Billington R, Keseler IM, Kothari A, Krummenacker M, Midford PE, Ong WK, Paley S, Subhraveti P, Karp PD; ''The MetaCyc database of metabolic pathways and enzymes - a 2019 update.''; Nucleic Acids Res, 2020 PubMed Europe PMC Scholia
  7. Caspi R; ''Pathway: dermatan sulfate biosynthesis''; , 2010
  8. Caspi R; ''Pathway: superpathway of heparan sulfate biosynthesis''; https://metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6564&detail-level=2, 2010
  9. Caspi R; ''Pathway: chondroitin biosynthesis''; https://biocyc.org/HUMAN/NEW-IMAGE?type=PATHWAY&object=PWY-6566, 2010
  10. Caspi R; ''Pathway: chondroitin sulfate biosynthesis''; https://metacyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6567&detail-level=2, 2010
  11. Karp PD, Billington R, Caspi R, Fulcher CA, Latendresse M, Kothari A, Keseler IM, Krummenacker M, Midford PE, Ong Q, Ong WK, Paley SM, Subhraveti P; ''The BioCyc collection of microbial genomes and metabolic pathways.''; Brief Bioinform, 2019 PubMed Europe PMC Scholia

History

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141851view02:52, 25 November 2025EweitzEconomize layout
141850view02:48, 25 November 2025EweitzEconomize layout
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141843view02:34, 25 November 2025EweitzAlign nodes
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141841view02:31, 25 November 2025EweitzRefine group modeling
141840view02:04, 25 November 2025EweitzStack nodes
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141837view01:53, 25 November 2025EweitzRemove deprecated metadata field
141836view01:53, 25 November 2025EweitzEconomize layout
134439view23:45, 21 July 2024EweitzOntology Term : 'glycosaminoglycan metabolic pathway' added !
134438view23:45, 21 July 2024EweitzStandardize case, economize layout
126912view19:34, 2 July 2023JuliabladOntology Term : 'fibroblast' added !
126911view19:34, 2 July 2023JuliabladOntology Term : 'classic metabolic pathway' added !
126910view19:32, 2 July 2023JuliabladNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
3-O-(β-D-xylosyl)-L-seryl-[protein]MetaboliteC02399 (KEGG Compound)
3-β-D-galactosyl-4-β-D-galactosyl -O-β-D-xylosyl-[protein]MetaboliteC04825 (KEGG Compound)
3-β-D-glucosyluronate-3-β-D-galactosyl -4-β-D-galactosyl-O-β-D-xylosyl-[protein]Metabolite80007 (ChEBI)
3-β-D-glucosyluronate-3-β-D-galactosyl -4-β-D-galactosyl-O-β-D-xylosyl-[protein]MetaboliteC04903 (KEGG Compound)
4-β-D-galactosyl-O-β-D-xylosyl-[protein]Metabolite25245405 (PubChem-compound)
B3GALT6GeneProductENSG00000176022 (Ensembl)
B3GAT1GeneProductENSG00000109956 (Ensembl)
B3GAT2GeneProductENSG00000112309 (Ensembl)
B3GAT3GeneProductENSG00000149541 (Ensembl)
B4GALT7GeneProductENSG00000027847 (Ensembl)
CHPF2GeneProductENSG00000033100 (Ensembl)
CHPFGeneProductENSG00000123989 (Ensembl)
CHST11GeneProductENSG00000171310 (Ensembl)
CHST12GeneProductENSG00000136213 (Ensembl)
CHST13GeneProductENSG00000180767 (Ensembl)
CHST14GeneProductENSG00000169105 (Ensembl)
CHST15GeneProductENSG00000182022 (Ensembl)
CHST1GeneProductENSG00000175264 (Ensembl)
CHST3GeneProductENSG00000122863 (Ensembl)
CHST7GeneProductENSG00000147119 (Ensembl)
CHSY1GeneProductENSG00000131873 (Ensembl)
CHSY3GeneProductENSG00000198108 (Ensembl)
CSGALNACT1GeneProductENSG00000147408 (Ensembl)
CSGALNACT2GeneProductENSG00000169826 (Ensembl)
Chondroitin-[core protein]Metabolite16137 (ChEBI)
DSEGeneProductENSG00000111817 (Ensembl)
Deacetylated heparosan-[core protein]MetaboliteC02834 (KEGG Compound)
Dermatan-NAcGal-4-sulfatesMetaboliteMetaNetX: MXNM96191
Dermatan-NAcGal-46-disulfates MetaboliteMetaNetX: MXNM96257
Dermatan-SulfateMetabolite18376 (ChEBI)
Dermatan-[core protein]Metabolite4439 (ChEBI)
Dermatan-sulfate-L-IdoA2SMetaboliteMetaNetX: MNXM7277
EXT1GeneProductENSG00000182197 (Ensembl)
EXT2GeneProductENSG00000151348 (Ensembl)
EXTL1GeneProductENSG00000158008 (Ensembl)
EXTL2GeneProductENSG00000162694 (Ensembl)
EXTL3GeneProductENSG00000012232 (Ensembl)
GLCEGeneProductENSG00000138604 (Ensembl)
GalNAc-GlcA-Gal-Gal-Xyl-ProteinsMetaboliteMetaNetX: MXNM18007
GalNAc-GlcA-GalNAc- GlcA-Gal-Gal-Xyl-PrMetaboliteMetaNetX: MXNM148368
GlcA-GalNAc-GlcA-Gal-Gal-Xyl-ProteinsMetaboliteMetaNetX: MXNM148183
GlcA-GlcNAc-GlcA-Gal-Gal-Xyl-Protein MetaboliteMetaNetX: MNXM148103
GlcNAc-GlcA-GlcNAc-GlcA -Gal-Gal-Xyl-CoreMetaboliteMetaNetX: MNXM148048
HS2ST1GeneProductENSG00000153936 (Ensembl)
HS3ST1GeneProductENSG00000002587 (Ensembl)
HS3ST2GeneProductENSG00000122254 (Ensembl)
HS3ST3A1GeneProductENSG00000153976 (Ensembl)
HS3ST3B1GeneProductENSG00000125430 (Ensembl)
HS6ST1GeneProductENSG00000136720 (Ensembl)
HS6ST2GeneProductENSG00000171004 (Ensembl)
HS6ST3GeneProductENSG00000185352 (Ensembl)
Heparan-Glc-N-3-6-trisulfateMetaboliteMetaNetX: MNXM18334
Heparan-GlcN-6-N-bisulfateMetaboliteMetaNetX: MNXM11794
Heparan-sulfate-3-N-disulfateMetaboliteMetaNetX: MNXM8703
Heparan-sulfate-L-IdoA-2SMetaboliteMetaNetX: MNXM96199
Heparosan-[core protein]Metabolite24500 (ChEBI)
NDST1GeneProductENSG00000070614 (Ensembl)
NDST2GeneProductENSG00000166507 (Ensembl)
NDST3GeneProductENSG00000164100 (Ensembl)
NDST4GeneProductENSG00000138653 (Ensembl)
UDP-N-acetyl-α-D-galactosamineMetabolite67138 (ChEBI)
UDP-α-D-galactoseMetabolite66914 (ChEBI)
UDP-α-D-glucuronateMetabolite58052 (ChEBI)
UDP-α-D-xyloseMetabolite57632 (ChEBI)
USTGeneProductENSG00000111962 (Ensembl)
XYLT1GeneProductENSG00000103489 (Ensembl)
XYLT2GeneProductENSG00000015532 (Ensembl)
[Heparan sulfate] containing GlcNSMetabolite13555 (ChEBI)
[Heparosan]-containing α-L-iduronateMetabolite17174 (ChEBI)
chondroitin 4'-sulfateMetabolite18250 (ChEBI)
chondroitin 6'-sulfateMetabolite18296 (ChEBI)
heparin-glucosamine-3-O-sulfateMetaboliteC04072 (KEGG Compound)

Annotated Interactions

No annotated interactions

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