Review of glycosaminoglycan metabolic process (GO:0030203) and proteoglycan metabolic process (GO:0006029) branches

[rozaru]

There are several issues with these 2 branches. Several terms have their definitions and Xrefs that need to be updated, other terms need to be made obsolete and some new terms are needed. I will add the requests to this thread gradually as some will depend on the decision made.

Background

Glycosaminoglycans (GAG) are polysaccharides composed of repeating disaccharides with variable sulfation levels. They are classified according to the repeating disaccharide subunit.

• chondroitin sulfate (CS) (glucuronic acid and N-acetylgalactosamine)
• dermatan sulfate (DS) (iduronic acid or glucuronic acid and N-acetylgalactosamine)
• heparan sulfate/heparin (HS) (iduronic acid or glucuronic acid and N-acetylglucosamine)
• keratan sulfate (KS) (galactose and N-acetylglucosamine)
• hyaluronan (HA) (glucuronic acid and N-acetylglucosamine)
• peptidoglycan (N-acetylglucosamine and N-acetylmuramic acid) made by Bacteria

Apart from hyaluronan and bacterial peptidoglycan, GAG are covalently bound through a linkage region to Ser, Thr or Asp to core proteins to produce proteoglycans (PGs)

For chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate/heparin (HS) and keratan sulfate (KS), the sugar units are added sequentially and directly to the protein.

The synthesis involved 2 mains steps:

• the formation of the linear disaccharide repeats chain
• the post-elongation modification, including epimerisation, sulfation Hyaluronan is not sulfated.

CS, DS and HS starts with the synthesis of a common tetrasacchardide linker. Reactome, KEGG and MetaCyc has separate pathway for this.

heparan sulfate and heparin differs by their levels of sulfation. It's seems that heparin is made mainly by mammals (not sure).

For a review: Book chapter Below is an example of the synthesis of chondroitin sulfate proteoglycan in Drosophila to give an idea.