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.

[rozaru]

Currently there are these 2 branches that cover GAG:

id: GO:0030203 glycosaminoglycan metabolic process def: "The chemical reactions and pathways involving glycosaminoglycans, any of a group of polysaccharides that contain amino sugars." [ISBN:0192800981]

id: GO:0006029 proteoglycan metabolic process def: "The chemical reactions and pathways involving proteoglycans, any glycoprotein in which the carbohydrate units are glycosaminoglycans." [GOC:mah, ISBN:0198506732]

1. For CS, DS, HS and KS that are directly synthesised on the protein, the annotation will go to the respective children terms of proteoglycan metabolic process. However, a variation of these terms exists under glycosaminoglycan metabolic process. In other words, what is the difference between 'chondroitin sulfate biosynthetic process' and chondroitin sulfate proteoglycan biosynthetic process, for example?

2. Preliminary definition update for GO:0030203 glycosaminoglycan metabolic process The chemical reactions and pathways involving glycosaminoglycans, any long unbranched polysaccharides consisting of a repeating disaccharide unit made of an N-acetyl-hexosamine and a hexose or hexuronic acid, either or both of which are often sulfated.

• [ ] Obsolete GO:0046350 galactosaminoglycan metabolic process and children There is no annotation currently made to these terms. According to the literature so far there are 3 types, chondroitin sulfate, dermatan sulfate and fucosylated chondroitin sulfate (PMID: 17239763), that would be part of galactosaminoglycans. Their corresponding GO terms are not children of GO:0046350 at the moment. This term seems to be an unnecessary grouping term. There is already a grouping term (mucopolysaccharide metabolic process) for all the GAG that are not bacterial proteoglycan.