Beta-Oxidation of (13Z)-octadecenoyl-CoA

Current behavior:

MAR03406: (13Z)-octadecenoyl-CoA [m] + 8 CoA [m] + 7 FAD [m] + 8 H2O [m] + 8 NAD+ [m] ⇒ 7 FADH2 [m] + 8 H+ [m] + 8 NADH [m] + 9 acetyl-CoA [m], GPR: ACAA1 or HSD17B10 or ACADVL or HADHA or ACADL or ACADM or ECHS1 or HADHB or HADH or ACAA2 or ACAD9 currently represents all rounds of β-oxidation of (13Z)-octadecenoyl-CoA in a single step.

Expected behavior:

To be more consistent with the representation of β-oxidation of other fatty acids, I think MAR03406 should be split up into a series of other reactions that each represent at most one full round of β-oxidation that eventually merge with the other “higher-resolution” β-oxidation reactions.

Proposed changes:

[ ] Create new metabolites to represent (11Z)-hexadecenoyl-CoA, (9Z)-tetradecenoyl-CoA, (7Z)-dodecenoyl-CoA, (5Z)-decenoyl-CoA, and (3Z)-octenoyl-CoA in mitochondria
[ ] Edit MAR03406 to represent a single round of β-oxidation: (13Z)-octadecenoyl-CoA + FAD + H₂O + CoA -> (11Z)-hexadecenoyl-CoA + FADH₂ + NADH + H⁺ + acetyl-CoA, GPR: (ACAD9 or ACADL or ACADVL) and HADHA and HADHB
[ ] Create a new reaction: (11Z)-hexadecenoyl-CoA + FAD + H₂O + CoA -> (9Z)-tetradecenoyl-CoA + FADH₂ + NADH + H⁺ + acetyl-CoA, GPR: (ACAD9 or ACADL or ACADVL) and HADHA and HADHB
[ ] Create a new reaction: (9Z)-tetradecenoyl-CoA + FAD + H₂O + CoA -> (7Z)-dodecenoyl-CoA + FADH₂ + NADH + H⁺ + acetyl-CoA, GPR: (ACAD9 or ACADL or ACADVL) and ECHS1 and (HADH or HSD17B10) and (ACAA2 or SCP2)
[ ] Create a new reaction: (7Z)-dodecenoyl-CoA + FAD + H₂O + CoA -> (5Z)-decenoyl-CoA + FADH₂ + NADH + H⁺ + acetyl-CoA, GPR: (ACAD9 or ACADL or ACADVL) and ECHS1 and (HADH or HSD17B10) and (ACAA2 or SCP2)
[ ] Create a new reaction: (5Z)-decenoyl-CoA + FAD + H₂O + CoA -> (3Z)-octenoyl-CoA + FADH₂ + NADH + H⁺ + acetyl-CoA, GPR: (ACAD9 or ACADL) and ECHS1 and (HADH or HSD17B10) and (ACAA2 or SCP2) (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)-octenoyl-CoA <-> (2E)-octenoyl-CoA (MAM00059m), GPR: ECI1 or ECI2

SysBioChalmers / Human-GEM