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feat: enable collagen secretion and remove duplicate MAR09553#1043

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fix/collagen-secretion
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feat: enable collagen secretion and remove duplicate MAR09553#1043
edkerk wants to merge 2 commits into
developfrom
fix/collagen-secretion

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@edkerk edkerk commented Jul 11, 2026

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Main improvements in this PR:

As reported in #335, the collagen synthesis pathway (MAR06983 → MAR06984 → MAR06985) ended at the dead-end metabolite 1,2-D-glucosyl-5-D-(galactosyloxy)-L-lysine-procollagen (MAM00232c) and could not carry flux, and MAR09553 was a redundant duplicate of MAR06983.

  • Remove MAR09553 (duplicate of MAR06983; its substrate procollagen-L-lysine MAM02768c was a dead-end input) and the orphaned MAM02768c (moved to the deprecated lists).
  • Add secretion of the final procollagen precursor: MAM00232e, a transport MAR20192 (MAM00232c → MAM00232e) and an exchange MAR20193, modelled like the existing hyaluronate secretion. This gives the collagen pathway a sink so it carries flux.

A general secreted-protein-export framework and collagen proline hydroxylation are cell-context-specific and out of scope for the generic Human-GEM; they are left for context-specific / specialised models.

I hereby confirm that I have:

  • Tested my code on my own computer for running the model
  • Selected develop as a target branch
  • Any removed reactions and metabolites have been moved to the corresponding deprecated identifier lists

edkerk and others added 2 commits July 11, 2026 17:24
The collagen synthesis pathway (MAR06983 -> MAR06984 -> MAR06985) ended
at the dead-end metabolite 1,2-D-glucosyl-5-D-(galactosyloxy)-L-lysine-
procollagen (MAM00232c), so it could not carry flux. MAR09553 was a
redundant duplicate of MAR06983 (same product, same GPR) whose substrate
procollagen-L-lysine (MAM02768c) was itself a dead-end input.

- Remove MAR09553 and its orphaned dead-end substrate MAM02768c
  (moved to the deprecated lists).
- Add secretion of the final procollagen precursor: MAM00232e, a
  transport MAR20192 (MAM00232c -> MAM00232e) and an exchange MAR20193,
  modelled like the existing hyaluronate secretion, giving the collagen
  pathway a sink so it can carry flux.

A general secreted-protein-export framework and collagen proline
hydroxylation are out of scope for the generic Human-GEM and left for
context-specific / specialised models.
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This PR has been automatically tested with GH Actions. Here are the results of the quality-control tests:

MACAW: dead-end and duplicate tests

Starting dead-end test...
 - Found 1380 dead-end metabolites.
 - Found 1137 reactions incapable of sustaining steady-state fluxes in either direction due to these dead-ends.
 - Found 1369 reversible reactions that can only carry steady-state fluxes in a single direction due to dead-ends.
Starting duplicate test...
 - Skipping redox duplicates because no redox_pairs and/or proton_ids were provided.
 - Found 377 reactions that were some type of duplicate:
   - 0 were completely identical to at least one other reaction.
   - 13 involve the same metabolites but go in the opposite direction or have the opposite reversibility as at least one other reaction.
   - 377 involve the same metabolites but with different coefficients as at least one other reaction.

Mass and charge balance

Unbalanced reactions (excluding boundary and biomass): 277 (87 mass, 240 charge)

More detailed output is committed to data/testResults/ (macaw_results.csv and balance_results.csv).

Note: In the case of multiple test runs, this post will be edited.

@edkerk edkerk added this to the 2.1.0 milestone Jul 11, 2026
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