Duplicate Beta-oxidation Reactions for Decanoyl-CoA

[Devlin-Moyer]

Current behavior:

There are several partially redundant sets of reactions representing the beta-oxidation of decanoyl-CoA to octanoyl-CoA:

ID	Reaction	Genes	Notes
MAR03142	FAD [m] + decanoyl-CoA [m] ⇒ (2E)-decenoyl-CoA [m] + FADH2 [m]	ACADM or ACAD9	Step 1
MAR03143	(2E)-decenoyl-CoA [m] + H2O [m] ⇒ (S)-hydroxydecanoyl-CoA [m]	HADHA and EHHADH and ECHS1	Step 2
MAR03144	(S)-hydroxydecanoyl-CoA [m] + NAD+ [m] ⇒ 3-oxodecanoyl-CoA [m] + H+ [m] + NADH [m]	HSD17B10 and HADHA and HADH	Step 3
MAR03146	3-oxodecanoyl-CoA [m] + CoA [m] ⇒ acetyl-CoA [m] + octanoyl-CoA [m]	HADHA and HADHB and ACAA2	Step 4
MAR05019	FAD [m] + H2O [m] + decanoyl-CoA [m] ⇒ (S)-hydroxydecanoyl-CoA [m] + FADH2 [m]	ACADM and ECHS1	Steps 1 and 2
MAR04967	(2E)-decenoyl-CoA [m] + CoA [m] + H2O [m] + NAD+ [m] ⇒ H+ [m] + NADH [m] + acetyl-CoA [m] + octanoyl-CoA [m]	ECHS1 and HADH and ACAA2	Steps 2-4
MAR05024	CoA [m] + FAD [m] + H2O [m] + NAD+ [m] + decanoyl-CoA [m] ⇒ FADH2 [m] + H+ [m] + NADH [m] + acetyl-CoA [m] + octanoyl-CoA [m]	ACADM and ECHS1 and HADH and ACAA2	Steps 1-4

Expected feature/value/output:

MAR03142, MAR03143, MAR03144, and MAR03146 accurately represent each step of beta-oxidation, so I think they should be kept and MAR05019, MAR04967, and MAR05024 should be removed for being redundant with various subsets of those four reactions.

[haowang-bioinfo]

the proposed changes seem rational

by the way, if the GPRs should be modified together or another time?

[Devlin-Moyer]

#634 would remove EHHADH from the GPR of MAR03143, since EHHADH is a peroxisomal enzyme, but if you think it makes sense, it would be easy enough to make that change here and remove it from the list in #634. The only other change I would make is adding ACADL (ENSG00000115361) to the GPR of MAR03142, since Uniprot cites a few papers that found it was capable of using decanoyl-CoA as a substrate. Oh and I guess you could make an argument that HADHA should be removed from the GPR of MAR03146, because while it forms a complex with HADHB, the 3-oxoacyl-thiolysis activity is only in the part formed by HADHB.

[haowang-bioinfo]

to speed up the fixing and avoid potential errors and delays, maybe first just focus on resolving the duplication reactions, which appear to be redundant in beta-oxidation pathways of HumanGEM

[Devlin-Moyer]

yea I was kind of thinking that, once I feel like I've resolved all of these duplicates, it'd make sense to go through and systematically assess the GPRs of the remaining reactions to make sure everything checks out

[haowang-bioinfo]

fixed by #789