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DECR1 and DECR2 use NADPH, not NADH #736

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Devlin-Moyer opened this issue Dec 3, 2023 · 5 comments
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DECR1 and DECR2 use NADPH, not NADH #736

Devlin-Moyer opened this issue Dec 3, 2023 · 5 comments
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@Devlin-Moyer
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Devlin-Moyer commented Dec 3, 2023

Current behavior:

These are all reactions currently in Human-GEM that use NADH to reduce 2,4-dienoyl-CoAs and are associated with DECR1 and/or DECR2:

ID Reaction
MAR03322 2-trans-4-cis-decadienoyl-CoA [x] + H+ [x] + NADH [x] --> NAD+ [x] + trans-3-decenoyl-CoA [x]
MAR03296 2-trans-4-cis-decadienoyl-CoA [m] + H+ [m] + NADH [m] --> NAD+ [m] + trans-3-decenoyl-CoA [m]
MAR06433 11-carboxy-alpha-tocotrienol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 9-carboxy-alpha-tocotrienol [m] + acetyl-CoA [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m]
MAR06448 11-carboxy-gamma-tocotrienol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 9-carboxy-gamma-tocotrienol [m] + acetyl-CoA [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m]

Expected behavior:

DECR1 (the mitochondrial enzyme) and DECR2 (the peroxisomal equivalent) both appear to be exclusively capable of using NADPH and not NADH to catalyze this reaction. MAR04970 and MAR04974 already represent NADPH-dependent equivalents of MAR03296 and MAR03322, respectively, so MAR03322 and MAR03296 can just be removed. The other two have a number of other problems, which I address separately in #738

Proposed changes:

  • Remove MAR03322 for being a less accurate version of MAR04974
  • Remove MAR03296 for being a less accurate version of MAR04970
@Devlin-Moyer Devlin-Moyer changed the title Near-Duplicate Beta Oxidation Reactions DECR1 and DECR2 use NADPH, not NADH Dec 10, 2023
@haowang-bioinfo
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haowang-bioinfo commented Dec 26, 2023

DECR1 (the mitochondrial enzyme) and DECR2 (the peroxisomal equivalent) both appear to be exclusively capable of using NADPH and not NADH to catalyze this reaction. MAR04970 and MAR04974 already represent NADPH-dependent equivalents of MAR03296 and MAR03322, respectively, so MAR03322 and MAR03296 can just be removed.

yes, it does appear that the NAD versions (MAR03322 and MAR03296) should be removed.

additionally and relevant to this, MAR04005[c] (the cytosol version of MAR04970[m] and MAR04974[x]) doesn't make sense and should also be removed?

@Devlin-Moyer
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yes it does look like MAR04005 is isolated and there's no reason to believe it'd happen in the cytosol, so it makes sense to remove it along with MAM00678c and MAM03035c (since MAR04005 is the only reaction either of those metabolites participate in)

@haowang-bioinfo
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MAR04005 is removed by fa52bf0 in #788

@haowang-bioinfo
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MAM00678c and MAM03035c are now removed by 1e2fac9

@haowang-bioinfo
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fixed by #788

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