From 30a3a9f170f52bcb375cc5221cfdb4594f7943ba Mon Sep 17 00:00:00 2001 From: Eduard Kerkhoven Date: Sat, 11 Jul 2026 14:27:15 +0200 Subject: [PATCH 1/2] feat: add cellular succinate export via MCT proton symport (#424) 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. --- model/Human-GEM.yml | 14 ++++++++++++++ model/reactions.tsv | 1 + 2 files changed, 15 insertions(+) diff --git a/model/Human-GEM.yml b/model/Human-GEM.yml index 681c03b0..02366a25 100644 --- a/model/Human-GEM.yml +++ b/model/Human-GEM.yml @@ -245971,6 +245971,20 @@ - references: "PMID:11080211;PMID:1356223;PMID:14583610;PMID:16213501;PMID:7595668;PMID:8838581;PMID:9053810" - subsystem: "Alanine, aspartate and glutamate metabolism" - confidence_score: 0 + - !!omap + - id: "MAR20192" + - name: "succinate transport via proton symport" + - metabolites: !!omap + - MAM02039c: 1 + - MAM02039e: -1 + - MAM02943c: 1 + - MAM02943e: -1 + - lower_bound: -1000 + - upper_bound: 1000 + - gene_reaction_rule: "ENSG00000141526 or ENSG00000155380" + - references: "PMID:35363247" + - subsystem: "Transport reactions" + - confidence_score: 0 - genes: - !!omap - id: "ENSG00000000419" diff --git a/model/reactions.tsv b/model/reactions.tsv index e5b1099e..c326df2f 100644 --- a/model/reactions.tsv +++ b/model/reactions.tsv @@ -12876,3 +12876,4 @@ MAR20188 0 MAR20189 0 MAR20190 0 MAR20191 R00253 GLNS R00253C r0077 GLNS MNXR100024 HMR_3890 RCR10506 0 RHEA:16169 HMR_3890 +MAR20192 0 From 1c3a69ceda4ea101bd37fce26d4131f92908921b Mon Sep 17 00:00:00 2001 From: edkerk <7326655+edkerk@users.noreply.github.com> Date: Sat, 11 Jul 2026 12:33:47 +0000 Subject: [PATCH 2/2] chore: add macaw test result --- data/testResults/README.md | 2 +- data/testResults/macaw_results.csv | 1 + 2 files changed, 2 insertions(+), 1 deletion(-) diff --git a/data/testResults/README.md b/data/testResults/README.md index 68c1de51..c22602ee 100644 --- a/data/testResults/README.md +++ b/data/testResults/README.md @@ -4,7 +4,7 @@ The file here contains results from the [MACAW](https://github.com/Devlin-Moyer/ The test results shown here were obtained by the GitHub Actions run in: -- **PR #1029** (MACAW) +- **PR #1039** (MACAW) - **PR #973** (gene essentiality) The results will be updated by any subsequent pull request. Summary results are shown as a comment in the corresponding pull request. diff --git a/data/testResults/macaw_results.csv b/data/testResults/macaw_results.csv index 5b8d58da..36c4caea 100644 --- a/data/testResults/macaw_results.csv +++ b/data/testResults/macaw_results.csv @@ -12876,3 +12876,4 @@ MAR20188,MAM01098m <=> MAM01098c,MAM01098c;MAM01098m,ok,ok,ok,N/A MAR20189,MAM01329c + 2 MAM01824m + 5 MAM02039m --> MAM01328c + 2 MAM01826m + 4 MAM02039i,MAM01328c;MAM01329c,ok,ok,ok,N/A MAR20190,MAM01329c + MAM02039c + MAM02553c --> MAM01328c + MAM02552c,MAM01328c;MAM01329c,ok,ok,ok,N/A MAR20191,MAM01371m + MAM01974m + MAM02578m --> MAM01285m + MAM01975m + MAM02751m,ok,ok,ok,ok,N/A +MAR20192,MAM02039e + MAM02943e <=> MAM02039c + MAM02943c,ok,ok,ok,ok,N/A