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feat: add cellular succinate export via MCT proton symport#1039

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feat: add cellular succinate export via MCT proton symport#1039
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feat/succinate-export

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@edkerk edkerk commented Jul 11, 2026

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Main improvements in this PR:

As requested in #424, adds cellular export of succinate.

Human-GEM has three Na-coupled succinate import reactions across the plasma membrane (MAR09610, MAR04939, MAR04938) but no export, so cytosolic succinate could not be secreted (relevant for hypoxia).

  • Add MAR20192: succinate[c] + H+[c] <=> succinate[e] + H+[e], GPR SLC16A1 or SLC16A3 (ENSG00000155380 or ENSG00000141526), reversible, modelled on the existing lactate MCT reaction MAR05998. Reference PMID:35363247 (MCT-mediated succinate export).

Succinate secretion now works through the existing exchange reaction MAR09415. Mitochondrial succinate export is already possible via the reversible SLC25A10/SLC25A1 antiporters, so no mitochondrial reaction is added.

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

Human-GEM has three Na-coupled succinate import reactions across the
plasma membrane (MAR09610, MAR04939, MAR04938) but no export, so
cytosolic succinate could not be secreted. Succinate export is relevant
in hypoxia and is mediated by the monocarboxylate transporters MCT1
(SLC16A1) and MCT4 (SLC16A3) (PMID:35363247).

Add MAR20192, a reversible succinate + H+ symport across the plasma
membrane (GPR SLC16A1 or SLC16A3), modelled like the existing lactate
MCT reaction MAR05998. Secretion now works through the existing exchange
reaction MAR09415. Mitochondrial succinate export is already possible via
the reversible SLC25A10/SLC25A1 antiporters, so no mitochondrial reaction
is added.
@edkerk edkerk added this to the 2.1.0 milestone Jul 11, 2026
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This PR has been automatically tested with GH Actions. Here is the output of the MACAW test:

Starting dead-end test...
- Found 1384 dead-end metabolites.
- Found 1141 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.

This and a more detailed output from MACAW are also committed to data/testResults/.

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

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