Incorrect Beta-Oxidation Reaction for (4Z,7Z,10Z,13Z,16Z)-docosapentaenoyl-CoA

[Devlin-Moyer]

MAR00965 appears to represent a single round of beta-oxidation of (4Z,7Z,10Z,13Z,16Z)-docosapentaenoyl-CoA:

(4Z,7Z,10Z,13Z,16Z)-docosapentaenoyl-CoA [m] + CoA [m] + H2O [m] + NAD+ [m] + O2 [m] ⇒ (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA [m] + H+ [m] + H2O2 [m] + NADH [m] + acetyl-CoA [m], GPR: ACADM or ACADS

But one round of beta-oxidation of (4Z,7Z,10Z,13Z,16Z)-docosapentaenoyl-CoA (already represented by MAR05380 + MAR05404 + MAR05383 + MAR05378) produces 5,8,11,14-Eicosatetraenoyl Coenzyme A, not (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA. In addition, it reduces O₂ to H₂O₂, but is associated with ACADM and ACADS, the mitochondrial acyl-CoA dehydrogenases, which reduce FAD to FADH₂ (the peroxisomal acyl-CoA oxidases ACOX1, ACOX2, and ACOX3 reduce O₂ to H₂O₂), and it appears to represent all 4 steps of a single round of beta-oxidation, but is only associated with the acyl-CoA dehydrogenases that catalyze the first of those 4 steps.

Since MAR05380 + MAR05404 + MAR05383 + MAR05378 already accurately represent a single round of beta-oxidation of (4Z,7Z,10Z,13Z,16Z)-docosapentaenoyl-CoA, and (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA can also be (accurately) produced from (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA in MAR00970, I think MAR00965 should be removed.

MAR00970: (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA [m] + CoA [m] + H2O [m] + NAD+ [m] ⇒ (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA [m] + H+ [m] + NADH [m] + acetyl-CoA [m]

[haowang-bioinfo]

thanks for careful checking of this case

it does appear that MAR00965 is duplicate to MAR00970. But both probably should be removed based on annotation of ACADM and ACADS, or the GPR needs to be modified?

[Devlin-Moyer]

This paper found that ACAD9 was 1) localized to the inner mitochondrial membrane and 2) capable of oxidizing C22:6 (i.e. docosahexaenoyl-CoA). While (4Z,7Z,10Z,13Z,16Z)-docosapentaenoyl-CoA is C22:5 and not C22:6, it doesn't seem like much of a stretch to suggest that ACAD9 could catalyze MAR00970.

[Devlin-Moyer]

Ah I just realized that MAR00970 represents a full round of beta-oxidation, not just the first step, but following the rationale I presented in #772 for the GPR of MAR00923, I think the GPR of MAR00970 should be (ACADL or ACAD9) and (ECI1 or ECI2) and ECH1 and DECR1 and HADHA and HADHB

[Devlin-Moyer]

fixed in #794