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Checked against the current develop, three changes from modifyModel.m still apply to the general model:
MAR08514 (L-lactate:ferricytochrome-c oxidoreductase, GPR CYB5D1) should be deprecated. This is a yeast enzyme (CYB2, EC 1.1.2.3) with no clear human equivalent, and it moves electrons from cytosolic lactate directly to mitochondrial cytochrome c, bypassing complexes I and III.
MAR03859 (D-lactate:ferricytochrome-c oxidoreductase, LDHD) should be reviewed. LDHD is mitochondrial, but D-lactate, pyruvate and H+ are placed in the cytosol.
MAR05113 (alanine cytosol → mitochondria) should be reversible. It is the only mitochondrial alanine transport, so alanine made by mitochondrial GPT2 cannot leave.
fixNADHDirectionality.m addresses a problem that is still present: with all exchanges closed, the model converts NADH to NADPH for free, in the cytosol (e.g. MAR04316 + MAR02779) and in the mitochondria (e.g. MAR03802 + MAR03804). The HMR 2.00 list does not close this on its own, and five of its reactions would be blocked entirely. This will be handled as part of #1083.
Follow-up to #1093, in #1105 (open): The LDHD reaction MAR03859 keeps cytochrome c as acceptor, now supported by direct human data (PMID:38413804). The mitochondrial L-LDH MAR04280 is kept, with corrected references and a note that mitochondrial LDH is contested (two previous references did not support it). Details and evidence are in the comment on #1093.
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edkerk commentedon Sep 24, 2026
Checked against the current develop, three changes from
modifyModel.mstill apply to the general model:fixNADHDirectionality.maddresses a problem that is still present: with all exchanges closed, the model converts NADH to NADPH for free, in the cytosol (e.g. MAR04316 + MAR02779) and in the mitochondria (e.g. MAR03802 + MAR03804). The HMR 2.00 list does not close this on its own, and five of its reactions would be blocked entirely. This will be handled as part of #1083.fix: apply remaining modifyModel.m curations from #418 (#1093)
edkerk commentedon Sep 28, 2026
Follow-up to #1093, in #1105 (open): The LDHD reaction MAR03859 keeps cytochrome c as acceptor, now supported by direct human data (PMID:38413804). The mitochondrial L-LDH MAR04280 is kept, with corrected references and a note that mitochondrial LDH is contested (two previous references did not support it). Details and evidence are in the comment on #1093.
edkerk commentedon Oct 5, 2026
Fixed in Human 2.1.0.