MAR03413 represents all steps of the beta-oxidation of (8Z,11Z)-eicosadienoyl-CoA, as MAR03409 does for (6Z,9Z)-octadecadienoyl-CoA and MAR03414 for (5Z,8Z,11Z)-eicosatrienoyl-CoA. A single round of beta-oxidation of (8Z,11Z)-eicosadienoyl-CoA would produce (6Z,9Z)-octadecadienoyl-CoA, so MAR03413 is largely redundant with MAR03409. (6Z,9Z)-octadecadienoyl-CoA can also be converted to octanoyl-CoA in a single step via MAR00788, or Trans7,10-Hexadecadienoyl Coenzyme A (MAM03982m) via MAR06452.
Expected feature/value/output:
I think MAR03413 should be edited to represent a single round of beta-oxidation from (8Z,11Z)-eicosadienoyl-CoA to (6Z,9Z)-octadecadienoyl-CoA. MAR06452 misrepresents the beta-oxidation of (6Z,9Z)-octadecadienoyl-CoA; one round would produce (4Z,7Z)-hexadecadienoyl-CoA, not (7Z,10Z)-hexadecadienoyl-CoA, so I think it should be removed.
The first step in the beta-oxidation of (6Z,9Z)-octadecadienoyl-CoA would be oxidation to (2E,6Z,9Z)-octadecatrienoyl-CoA, which would also be an intermediate in the beta-oxidation of (5Z,8Z,11Z)-eicosatrienoyl-CoA. I think it makes sense to represent this convergence in the beta-oxidation pathways of (5Z,8Z,11Z)-eicosatrienoyl-CoA and (6Z,9Z)-octadecadienoyl-CoA by editing MAR03414 to only represent a single round of beta-oxidation from (5Z,8Z,11Z)-eicosatrienoyl-CoA to (3Z,6Z,9Z)-octadecatrienoyl-CoA, adding a new reaction that converts (3Z,6Z,9Z)-octadecatrienoyl-CoA to (2E,6Z,9Z)-octadecatrienoyl-CoA (which could be done by ECI1 or ECI2), and editing either MAR03409 or MAR00788 to just represent that first step of oxidizing (6Z,9Z)-octadecadienoyl-CoA to (2E,6Z,9Z)-octadecatrienoyl-CoA instead of multiple consecutive rounds of beta-oxidation. Neither (3Z,6Z,9Z)-octadecatrienoyl-CoA nor (2E,6Z,9Z)-octadecatrienoyl-CoA are currently represented by metabolites in Human-GEM, so both would have to be created.
To prevent these new metabolites from being dead ends, we'd also need to add:
(2E,6Z,9Z)-octadecatrienoyl-CoA + H2O + NAD+ + CoA -> (4Z,7Z)-hexadecadienoyl-CoA + NADH + H+ + acetyl-CoA, GPR: HADHA and HADHB
(3E,7Z)-hexadecadienoyl-CoA -> (2E,7Z)-hexadecadienoyl-CoA (MAM03019m), GPR: ECI1 or ECI2
At which point the remaining steps of beta-oxidation are already represented by MAR03231 + MAR03232 + MAR03233 + MAR03234 + MAR03235 + MAR03236 + MAR03237 + MAR03239 + MAR03136 + MAR03137 + MAR03139 + MAR03142 + MAR03143 + MAR03144 + MAR03146 + MAR03149 + MAR03150 + MAR03151 + MAR03153 + MAR03156 + MAR03157 + MAR03158 + MAR03160 + MAR03163 + MAR03164 + MAR03166 + MAR03885
Proposed changes:
[ ] Edit MAR03413 to be (8Z,11Z)-eicosadienoyl-CoA + FAD + H2O + NAD+ + CoA -> (6Z,9Z)-octadecadienoyl-CoA + FADH2 + NADH + H+ + acetyl-CoA, GPR: (ACAD9 or ACADL or ACADVL) and HADHA and HADHB
[ ] Remove MAR06452 for misrepresenting the beta-oxidation of (6Z,9Z)-octadecadienoyl-CoA
[ ] Create new metabolites to represent (3Z,6Z,9Z)-octadecatrienoyl-CoA, (2E,6Z,9Z)-octadecatrienoyl-CoA, (4Z,7Z)-hexadecadienoyl-CoA, (2E,4Z,7Z)-hexadecatrienoyl-CoA, and (3E,7Z)-hexadecadienoyl-CoA
[ ] Edit MAR03414 to be (5Z,8Z,11Z)-eicosatrienoyl-CoA + FAD + H2O + NAD+ + CoA -> (3Z,6Z,9Z)-octadecatrienoyl-CoA + FADH2 + NADH + H+ + acetyl-CoA, GPR: (ACAD9 or ACADL) and HADHA and HADHB (left ACADVL out of this GPR because this paper found that it only works with unsaturated substrates if the first double bond is no closer than carbon 6)
[ ] Create a new reaction: (3Z,6Z,9Z)-octadecatrienoyl-CoA <-> (2E,6Z,9Z)-octadecatrienoyl-CoA, GPR: ECI1 or ECI2
[ ] Edit MAR03409 to be (6Z,9Z)-octadecadienoyl-CoA + FAD -> (2E,6Z,9Z)-octadecatrienoyl-CoA + FADH2, GPR: ACAD9 or ACADL or ACADVL
[ ] Create a new reaction: (2E,6Z,9Z)-octadecatrienoyl-CoA + H2O + NAD+ + CoA -> (4Z,7Z)-hexadecadienoyl-CoA + NADH + H+ + acetyl-CoA, GPR: HADHA and HADHB
[ ] Create a new reaction: (4Z,7Z)-hexadecadienoyl-CoA + FAD -> (2E,4Z,7Z)-hexadecatrienoyl-CoA + FADH2, GPR: ACAD9 or ACADL
[ ] Create a new reaction: (2E,4Z,7Z)-hexadecatrienoyl-CoA + NADPH + H+ -> (3E,7Z)-hexadecadienoyl-CoA + NADP+, GPR: DECR1
[ ] Create a new reaction: (3E,7Z)-hexadecadienoyl-CoA -> (2E,7Z)-hexadecadienoyl-CoA (MAM03019m), GPR: ECI1 or ECI2
[ ] Remove MAR00788 for being a duplicate of MAR03409 + the four new reactions directly above this + MAR03231 + MAR03232 + MAR03233 + MAR03234 + MAR03235 + MAR03236 + MAR03237 + MAR03239 + MAR03136 + MAR03137 + MAR03139 + MAR03142 + MAR03143 + MAR03144 + MAR03146
Current behavior:
MAR03413represents all steps of the beta-oxidation of (8Z,11Z)-eicosadienoyl-CoA, asMAR03409does for (6Z,9Z)-octadecadienoyl-CoA andMAR03414for (5Z,8Z,11Z)-eicosatrienoyl-CoA. A single round of beta-oxidation of (8Z,11Z)-eicosadienoyl-CoA would produce (6Z,9Z)-octadecadienoyl-CoA, soMAR03413is largely redundant withMAR03409. (6Z,9Z)-octadecadienoyl-CoA can also be converted to octanoyl-CoA in a single step viaMAR00788, or Trans7,10-Hexadecadienoyl Coenzyme A (MAM03982m) viaMAR06452.Expected feature/value/output:
I think
MAR03413should be edited to represent a single round of beta-oxidation from (8Z,11Z)-eicosadienoyl-CoA to (6Z,9Z)-octadecadienoyl-CoA.MAR06452misrepresents the beta-oxidation of (6Z,9Z)-octadecadienoyl-CoA; one round would produce (4Z,7Z)-hexadecadienoyl-CoA, not (7Z,10Z)-hexadecadienoyl-CoA, so I think it should be removed.The first step in the beta-oxidation of (6Z,9Z)-octadecadienoyl-CoA would be oxidation to (2E,6Z,9Z)-octadecatrienoyl-CoA, which would also be an intermediate in the beta-oxidation of (5Z,8Z,11Z)-eicosatrienoyl-CoA. I think it makes sense to represent this convergence in the beta-oxidation pathways of (5Z,8Z,11Z)-eicosatrienoyl-CoA and (6Z,9Z)-octadecadienoyl-CoA by editing
MAR03414to only represent a single round of beta-oxidation from (5Z,8Z,11Z)-eicosatrienoyl-CoA to (3Z,6Z,9Z)-octadecatrienoyl-CoA, adding a new reaction that converts (3Z,6Z,9Z)-octadecatrienoyl-CoA to (2E,6Z,9Z)-octadecatrienoyl-CoA (which could be done by ECI1 or ECI2), and editing eitherMAR03409orMAR00788to just represent that first step of oxidizing (6Z,9Z)-octadecadienoyl-CoA to (2E,6Z,9Z)-octadecatrienoyl-CoA instead of multiple consecutive rounds of beta-oxidation. Neither (3Z,6Z,9Z)-octadecatrienoyl-CoA nor (2E,6Z,9Z)-octadecatrienoyl-CoA are currently represented by metabolites in Human-GEM, so both would have to be created.To prevent these new metabolites from being dead ends, we'd also need to add:
HADHA and HADHBACAD9 or ACADLDECR1MAM03019m), GPR:ECI1 or ECI2At which point the remaining steps of beta-oxidation are already represented by
MAR03231+MAR03232+MAR03233+MAR03234+MAR03235+MAR03236+MAR03237+MAR03239+MAR03136+MAR03137+MAR03139+MAR03142+MAR03143+MAR03144+MAR03146+MAR03149+MAR03150+MAR03151+MAR03153+MAR03156+MAR03157+MAR03158+MAR03160+MAR03163+MAR03164+MAR03166+MAR03885Proposed changes:
MAR03413to be (8Z,11Z)-eicosadienoyl-CoA + FAD + H2O + NAD+ + CoA -> (6Z,9Z)-octadecadienoyl-CoA + FADH2 + NADH + H+ + acetyl-CoA, GPR:(ACAD9 or ACADL or ACADVL) and HADHA and HADHBMAR06452for misrepresenting the beta-oxidation of (6Z,9Z)-octadecadienoyl-CoAMAR03414to be (5Z,8Z,11Z)-eicosatrienoyl-CoA + FAD + H2O + NAD+ + CoA -> (3Z,6Z,9Z)-octadecatrienoyl-CoA + FADH2 + NADH + H+ + acetyl-CoA, GPR:(ACAD9 or ACADL) and HADHA and HADHB(left ACADVL out of this GPR because this paper found that it only works with unsaturated substrates if the first double bond is no closer than carbon 6)ECI1 or ECI2MAR03409to be (6Z,9Z)-octadecadienoyl-CoA + FAD -> (2E,6Z,9Z)-octadecatrienoyl-CoA + FADH2, GPR:ACAD9 or ACADL or ACADVLHADHA and HADHBACAD9 or ACADLDECR1MAM03019m), GPR:ECI1 or ECI2MAR00788for being a duplicate ofMAR03409+ the four new reactions directly above this +MAR03231+MAR03232+MAR03233+MAR03234+MAR03235+MAR03236+MAR03237+MAR03239+MAR03136+MAR03137+MAR03139+MAR03142+MAR03143+MAR03144+MAR03146