Mitochondrial Beta-Oxidation Reactions That Reduce O2 to H2O2

[Devlin-Moyer]

Current behavior:

While working on #634, I noticed a few mitochondrial reactions in which an acyl-CoA was oxidized to a 2-trans-enoyl-CoA (the first step of beta-oxidation) that reduce O₂ to H₂O₂. As discussed in #607 and #639, the enzymes responsible for catalyzing these reactions reduce their FAD cofactors before eventually reducing ubiquinone to ubiquinol (in mitochondria) or reducing O₂ to H₂O₂ (in peroxisomes), and we decided to edit all of these reactions to reduce FAD to FADH₂ and have separate reactions for redox between FAD and ubiquinone or O₂. This is a list of all mitochondrial reactions currently in Human-GEM that reduce O₂ to H₂O₂:

ID	Reaction	Notes
MAR01253	20-CoA-20-oxo-LTB4 [m] + O2 [m] --> (18E)-20-oxo-20-CoA-LTB4 [m] + H2O2 [m]	not mentioned in other issues
MAR01270	10,11-dihydro-LTB4-CoA [m] + O2 [m] --> 5(S),12(R)-dihydroxy-eicosa-2,8-trans-6,14-cis-tetraenoyl-CoA [m] + H2O2 [m]	not mentioned in other issues
MAR03997	O2 [m] + Cis-6-Dodecenoyl Coenzyme A [m] --> H2O2 [m] + trans,cis-lauro-2,6-dienoyl-CoA [m]	not mentioned in other issues
MAR03456	(4Z,7Z,10Z)-hexadecatrienoyl-CoA [m] + O2 [m] --> (2E,4Z,7Z,10Z)-hexadecatetraenoyl-CoA [m] + H2O2 [m]	mentioned in #761, but proposed changes don’t affect it
MAR01161	5-oxo-12(R)-hydroxy-eicosa-(8E,10E,14Z)-trienoyl-CoA [m] + O2 [m] --> 5-oxo-12(R)-hydroxy-eicosa-(2E,8E,10E,14Z)-tetraenoyl-CoA [m] + H2O2 [m]	mentioned in #749, but proposed changes don’t affect it
MAR01204	5-oxo-12(S)-hydroxy-eicosa-(8E,10E,14Z)-trienoyl-CoA [m] + O2 [m] --> 5-oxo-12(S)-hydroxy-eicosa-(2E,8E,10E,14Z)-tetraenoyl-CoA [m] + H2O2 [m]	mentioned in #749, but proposed changes don’t affect it
MAR01175	8(R)-hydroxy-hexadeca-(4E,6E,10Z)-trienoate [m] + O2 [m] --> 8(R)-hydroxy-hexadeca-(2E,4E,6E,10Z)-tetraenoate [m] + H2O2 [m]	mentioned in #749, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR01180	6(R)-hydroxy-tetradeca-(4E,8Z)-dienoate [m] + O2 [m] --> 6(R)-hydroxy-tetradeca-(2E,4E,8Z)-trienoate [m] + H2O2 [m]	mentioned in #749, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR01217	8(S)-hydroxy-hexadeca-(4E,6E,10Z)-trienoate [m] + O2 [m] --> 8(S)-hydroxy-hexadeca-(2E,4E,6E,10Z)-tetraenoate [m] + H2O2 [m]	mentioned in #749, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR01223	6(S)-hydroxy-tetradeca-(4E,8Z)-dienoate [m] + O2 [m] --> 6(S)-hydroxy-tetradeca-(2E,4E,8Z)-trienoate [m] + H2O2 [m]	mentioned in #749, but proposed changes wouldn’t address the oxygen/peroxide problem
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]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06435	7-carboxy-alpha-tocotrienol [m] + ATP [m] + CoA [m] + 2 H2O [m] + O2 [m] --> 5-carboxy-alpha-chromanol [m] + acetyl-CoA [m] + AMP [m] + H+ [m] + H2O2 [m] + PPi [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06482	13-carboxy-alpha-tocopherol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 11-carboxy-alpha-chromanol [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m] + propanoyl-CoA [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06484	11-carboxy-alpha-chromanol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 9-carboxy-alpha-chromanol [m] + acetyl-CoA [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06486	9-carboxy-alpha-chromanol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 7-carboxy-alpha-chromanol [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m] + propanoyl-CoA [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06488	7-carboxy-alpha-chromanol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 5-carboxy-alpha-chromanol [m] + acetyl-CoA [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06436	5-carboxy-alpha-chromanol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 3-carboxy-alpha-chromanol [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m] + propanoyl-CoA [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
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]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06451	7-carboxy-gamma-tocotrienol [m] + ATP [m] + CoA [m] + 2 H2O [m] + O2 [m] --> 5-carboxy-gamma-chromanol [m] + acetyl-CoA [m] + AMP [m] + H+ [m] + H2O2 [m] + PPi [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06453	5-carboxy-gamma-chromanol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> AMP [m] + gamma-carboxyethyl-hydroxychroman [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m] + propanoyl-CoA [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06470	13-carboxy-gamma-tocopherol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 11-carboxy-gamma-chromanol [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m] + propanoyl-CoA [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06471	11-carboxy-gamma-chromanol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 9-carboxy-gamma-chromanol [m] + acetyl-CoA [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06472	9-carboxy-gamma-chromanol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 7-carboxy-gamma-chromanol [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m] + propanoyl-CoA [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR06473	7-carboxy-gamma-chromanol [m] + ATP [m] + CoA [m] + 2 H2O [m] + NAD+ [m] + O2 [m] --> 5-carboxy-gamma-chromanol [m] + acetyl-CoA [m] + AMP [m] + 2 H+ [m] + H2O2 [m] + NADH [m] + PPi [m]	mentioned in #738, but proposed changes wouldn’t address the oxygen/peroxide problem
MAR00799	5 CoA [m] + gamma-linolenoyl-CoA [m] + 5 H2O [m] + 5 NAD+ [m] + 2 O2 [m] --> 5 acetyl-CoA [m] + 5 H+ [m] + 2 H2O2 [m] + 5 NADH [m] + octanoyl-CoA [m]	proposed to be removed in #763
MAR03366	arachidonyl-CoA [m] + O2 [m] --> 2-trans-cis,cis,cis,cis-4,8,11,14-eicosapentaenoyl-CoA [m] + H2O2 [m]	proposed to be removed in #737
MAR03371	cis,cis-myristo-5,8-dienoyl-CoA [m] + O2 [m] --> H2O2 [m] + trans-2-cis,cis-5,8-tetradecatrienoyl-CoA [m]	proposed to be removed in #737
MAR04003	4-cis-decenoyl-CoA [m] + O2 [m] --> 2-trans-4-cis-decadienoyl-CoA [m] + H2O2 [m]	proposed to be removed in #737
MAR00965	(4Z,7Z,10Z,13Z,16Z)-docosapentaenoyl-CoA [m] + CoA [m] + H2O [m] + NAD+ [m] + O2 [m] --> (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA [m] + acetyl-CoA [m] + H+ [m] + H2O2 [m] + NADH [m]	removed in #794

MAR02134, MAR02136, MAR04189, and MAR04755 also reduce mitochondrial oxygen to H₂O₂, but none of them are beta-oxidation reactions (i.e. they're associated with other enzymes that may actually directly reduce oxygen to H₂O₂), so I'm not addressing them here.

There are other problems with many of these reactions, which I address in other issues (hence the "Notes" column), but I figured it might be nice to have a single issue that addresses this specific problem in every reaction that has it.

Proposed changes:

Replace oxygen (MAR02630m) with FAD (MAM01802m) and hydrogen peroxide (MAM02041m) with FADH₂ (MAM01803m) in:

• MAR01253
• MAR01270
• MAR03997
• MAR03456
• MAR01161
• MAR01204
• MAR01175
• MAR01180
• MAR01217
• MAR01223
• MAR06433
• MAR06435
• MAR06482
• MAR06484
• MAR06486
• MAR06488
• MAR06436
• MAR06448
• MAR06451
• MAR06453
• MAR06470
• MAR06471
• MAR06472
• MAR06473