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SysBioChalmers / Human-GEM

The generic genome-scale metabolic model of Homo sapiens
https://sysbiochalmers.github.io/Human-GEM-guide/
Creative Commons Attribution 4.0 International
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Fixing collagen synthesis #335

Open CadavidJoseL opened 2 years ago

CadavidJoseL commented 2 years ago

Description of the issue:

All reactions pertaining to collagen synthesis in v1.10 (MAR06983, MAR06984, MAR06985, MAR09553) are dead-end reactions. Adding an export reaction to remove 1,2-D-glucosyl-5-D-(galactosyloxy)-L-lysine-procollagen[c] enables the reactions to carry flux, except for MAR09553 which seems to be a duplicate of MAR06983. Furthermore, collagen synthesis also involves proline residues, which are not captured in the rxns in the current HUMAN-GEM.

Expected feature/value/output:

Collagen production and secretion is an important feature of cells such as fibroblast, and it can be an important sink of aminoacids in such cells. Since other extracellular matrix components like hyaluronate can be produced by the model, I believe that curating and improving this set of reactions can be of value to the community. I am creating this issue in case someone else has thought of this problem or if anyone has any ideas on how to address it. I will start by looking at how other GEMs deal with collagen synthesis.

I hereby confirm that I have:

haowang-bioinfo commented 2 years ago

@CadavidJoseL very nice input.

can you please look into if there is any transporter(s) that assist the secretion of 1,2-D-glucosyl-5-D-(galactosyloxy)-L-lysine-procollagen?

CadavidJoseL commented 2 years ago

@Hao-Chalmers I'll have to look at this pathway in detail, it is more complicated than I thought. Procollagen seems to be exported in vesicles and it matures fully outside the cell. Glycosylation seems to be one of the final steps in the synthesis process, so for practical purposes maybe we consider 1,2-D-glucosyl-5-D-(galactosyloxy)-L-lysine-procollagen as the final collagen precursor to be exported. I am looking at fixing other gene associations in the HUMAN-GEM, and also at whether we can improve the collagen synthesis pathway in general, but I'll be a bit slow given my current time constraints.

CadavidJoseL commented 2 years ago

More generally, I found this paper (with input from your group) that looks at incorporating protein export. Maybe this is an even better thing to integrate?

mihai-sysbio commented 2 years ago

@CadavidJoseL did any idea crystallize?

CadavidJoseL commented 2 years ago

@mihai-sysbio other than my previous comment, I haven't been able to spend too long on this since I am trying to get experiments to graduate this year. Terribly sorry about this. If we want to address collagen synthesis only, that might be simpler, but if we want to incorporate more secreted proteins, it's much longer. If you have an idea of how to approach the problem systematically, I am happy to help with parts of it!