Textual definition update: heparin metabolic process and heparan sulfate metabolic process

[rozaru]

This is related to the review of glycosaminoglycan metabolic process (GO:0030203) and proteoglycan metabolic process (GO:0006029) branches ticket #28977

Heparin and heparan sulfate (HS) are polymers of iduronic acid/glucuronic acid and N-acetylglucosamine (PMID: 28653068)
their synthesis is the same they only differ by:

• their sulfate levels (2.3 sulfate groups per disaccharide in heparin and ∼0.8 sulfate groups per disaccharide in HS)

• their localisation

  • HS is ubiquitously found at the surface of all animal cells
  • heparin is produced and stored selectively in the secretory granules of connective-tissue mast cells (mammals only?)

• heparin synthesis begins on the serglycin core protein, followed by chain elongation and chain modification. In addition, the heparin chain is cleaved by heparanase (PMID: 39000302)

In summary, the genes involved in their synthesis/chain modification are likely to be the same.

Is it better to have one GO term for heparan sulfate and heparin or a separate GO term for each?

These are the current GO terms related to their metabolism belonging to glycosaminoglycan metabolic process (GO:0030203) or proteoglycan metabolic process (GO:0006029) branches:

id: GO:0030201
name: heparan sulfate proteoglycan metabolic process
def: "The chemical reactions and pathways involving any proteoglycan containing heparan sulfate, any member of a group of glycosaminoglycans that have repeat units consisting of alternating alpha-(1->4)-linked hexuronic acid and glucosamine residues, the former being a mixture of sulfated and nonsulfated D-glucuronic and L-iduronic acids, and the latter being either sulfated or acetylated on its amino group as well as sulfated on one of its hydroxyl groups." [GOC:mah, ISBN:0198506732]
synonym: "heparin proteoglycan metabolic process" RELATED []
is_a: GO:0006029 ! proteoglycan metabolic process

id: GO:0030202
name: heparin metabolic process
def: "The chemical reactions and pathways involving heparin, any member of a group of glycosaminoglycans found mainly as an intracellular component of mast cells. They are similar to heparan sulfates but are of somewhat higher average Mr (6000-20000) and contain fewer N-acetyl groups and more N-sulfate and O-sulfate groups; they may be attached in the same manner to protein, forming proteoglycans. They consist predominantly of alternating alpha-(1->4)-linked D-galactose and N-acetyl-D-glucosamine-6-sulfate residues." [GOC:mah, ISBN:0198506732]
synonym: "heparan sulfate metabolic process" RELATED []
intersection_of: GO:0008152 ! metabolic process
intersection_of: has_primary_input_or_output CHEBI:24505 ! heparins

Issues

• There is no heparan sulfate metabolic process

|__mucopolysaccharide metabolic process
           |__chondroitin sulfate metabolic process
           |__dermatan sulfate metabolic process
           |__heparin metabolic process
           |__hyaluronan metabolic process
           |__keratan sulfate metabolic process

Options:

1. Have a unique term : heparan sulfate/ heparin metabolic process
2. Have 2 separate terms: heparin metabolic process and heparan sulfate metabolic process

There is no heparin proteoglycan metabolic process

|__proteoglycan metabolic process                                                
	|__chondroitin sulfate proteoglycan metabolic process
	|__dermatan sulfate proteoglycan metabolic process
	|__heparan sulfate proteoglycan metabolic process

Options:

1. Update the current heparan sulfate proteoglycan metabolic process to include heparin: heparan sulfate/heparin proteoglycan metabolic process
2. Having 2 separate terms: heparan sulfate proteoglycan metabolic process and heparin sulfate proteoglycan metabolic process

Metabolic ressources:
In MetaCyc there is no specific pathway for heparin: superpathway of heparan sulfate biosynthesis
In Reactome, both are under the same pathway: Heparin sulfate/heparin (HS-GAG) metabolism
In KEGG both are under the same pathway: Glycosaminoglycan biosynthesis - heparan sulfate / heparin

[sjm41]

@rozaru

is this description of heparins in the current def of 'heparin metabolic process' true?
They consist predominantly of alternating alpha-(1->4)-linked D-galactose and N-acetyl-D-glucosamine-6-sulfate residues

Your original post of this ticket says they "are polymers of iduronic acid/glucuronic acid and N-acetylglucosamine"

[rozaru]

The current GO definition is wrong. Heparin as heparan sulfate is made of iduronic acid/glucuronic acid and N-acetylglucosamine that can sulfated.
Most of the definition for the glycosaminoglycan needs to be revised. I was hoping first to tidied up the branch and then once is done to update and make consistent the definition etc..