Current behavior:

MAR03416 represents all steps of beta-oxidation of (11Z)-docosenoyl-CoA in a single reaction, as MAR03411 does for 9-eicosenoyl-CoA and MAR03408 does for (7Z)-octadecenoyl-CoA. A single round of beta-oxidation of (11Z)-docosenoyl-CoA would produce 9-eicosenoyl-CoA, and one more round would produce (7Z)-octadecenoyl-CoA. The next two rounds would produce (5Z)-hexadecenoyl-CoA and (3Z)-tetradecenoyl-CoA, neither of which are currently present in Human-GEM. However, (2E)-tetradecenoyl-CoA is already present as MAM00066m, and ECI1 or ECI2 could convert (3Z)-tetradecenoyl-CoA into (2E)-tetradecenoyl-CoA in mitochondria.

Expected feature/value/output:

I think MAR03416, MAR03411, and MAR03408 should all be edited to represent one round of beta-oxidation each. This is simple enough to do for MAR03416 and MAR03411, but doing this for MAR03408 would require the creation of a new metabolite to represent (5Z)-hexadecenoyl-CoA. Making this new version of MAR03408 not be a dead-end would also require adding two more reactions and one metabolite to represent beta-oxidation of (5Z)-hexadecenoyl-CoA to (3Z)-tetradecenoyl-CoA and isomerization of (3Z)-tetradecenoyl-CoA to (2E)-tetradecenoyl-CoA (MAM00066m) by ECI1 or ECI2.

Proposed changes:

• Edit MAR03416 to be (11Z)-docosenoyl-CoA + FAD + H₂O + NAD⁺ + CoA -> 9-eicosenoyl-CoA + FADH₂ + NADH + H⁺ + acetyl-CoA, GPR: (ACAD9 or ACADL or ACADVL) and HADHA and HADHB
• Edit MAR03411 to be 9-eicosenoyl-CoA + FAD + H₂O + NAD⁺ + CoA -> (7Z)-octadecenoyl-CoA + FADH₂ + NADH + H⁺ + acetyl-CoA, GPR: (ACAD9 or ACADL or ACADVL) and HADHA and HADHB
• Create a new metabolite to represent mitochondrial (5Z)-hexadecenoyl-CoA (CHEBI:170092)
• Edit MAR03408 to be (7Z)-octadecenoyl-CoA + FAD + H₂O + NAD⁺ + CoA -> (5Z)-hexadecenoyl-CoA + FADH₂ + NADH + H⁺ + acetyl-CoA, GPR: (ACAD9 or ACADL or ACADVL) and HADHA and HADHB
• Create a new metabolite to represent mitochondrial (3Z)-tetradecenoyl-CoA
• Create a new reaction: (5Z)-hexadecenoyl-CoA + FAD + H₂O + NAD⁺ + CoA -> (3Z)-tetradecenoyl-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)-tetradecenoyl-CoA <-> (2E)-tetradecenoyl-CoA (MAM00066m), GPR: ECI1 or ECI2 (ENSG00000167969 or ENSG00000198721)