At the moment, 5,8,11,14,17-Eicosapentenoyl Coenzyme A (MAM03284m) (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA (MAM00103m) are different metabolites, but the changes proposed in #771 would remove MAM03284m and replace it with MAM00103m in all the reactions it currently participates in, so I'm not addressing that further in this issue.
I think it's clear that MAR00970, MAR03428, MAR09719, and MAR03430 are all duplicates of various subsets of the reactions between MAR05408 and MAR03885, so they should all be removed in favor of the more detailed series of reactions. MAR00818 is almost a duplicate of MAR05365 through MAR04984, except it incorrectly ends with octanoyl-CoA instead of 5-octenoyl-CoA (see #765 for a similar set of duplicates), so it should definitely be removed.
At first glance, MAR00923 just looks like an incorrect version of MAR05370, but I'm pretty sure it's supposed to represent the following (plausible, if slightly non-canonical) series of reactions:
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA -> (2E,5Z,8Z,11Z,14Z,17Z)-eicosahexaenoyl-CoA (by ACADL or ACAD9)
(2E,5Z,8Z,11Z,14Z,17Z)-eicosahexaenoyl-CoA -> (3Z,5Z,8Z,11Z,14Z,17Z)-eicosahexaenoyl-CoA (by ECI1 or ECI2)
So I don't think MAR00923 has to be removed, but its GPR should be changed to (ACADL or ACAD9) and (ECI1 or ECI2) and ECH1 and DECR1 and HADHA and HADHB.
MAR05365 represents one full round of beta-oxidation of beta-oxidation from (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA to (4Z,7Z,10Z,13Z)-hexadecatetraenoyl CoA, but the first step in that process would be oxidation by ACADL or ACAD9 to form (2E,6Z,9Z,12Z,15Z)-octadecapentaenoyl-CoA, i.e. MAM03195m, which is a reactant in MAR05369, which produces (4Z,7Z,10Z,13Z)-hexadecatetraenoyl CoA. To resolve this partial redundancy, I propose that MAR05365 be edited to just represent the first step of this round of beta-oxidation, i.e. (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + FAD -> (2E,9Z,12Z,15Z)-octadecapentaenoyl-CoA + FADH2 with a GPR of ACADL or ACAD9.
Proposed changes:
[ ] Change GPR of MAR00923 to (ENSG00000115361 or ENSG00000177646) and (ENSG00000167969 or ENSG00000198721) and ENSG00000104823 and ENSG00000104325 and ENSG00000084754 and ENSG00000138029
[ ] Change MAR05365 to MAM00108m + MAM01802m -> MAM03195m + MAM01803m, GPR: ENSG00000115361 or ENSG00000177646
[ ] Remove MAR00818 for being inaccurate
[ ] Remove MAR00970 for being a duplicate of MAR05408 + MAR05412 + MAR05410 + MAR05403
Current behavior:
There are a number of redundant beta-oxidation reactions for (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA:
MAR05408
MAR05412
MAR05410
MAR05403
MAR05376
MAR05370
MAR05369
MAR05298
MAR05312
MAR05306
MAR05242
MAR05177
MAR05090
MAR05083
MAR04978
MAR05001
MAR04988
MAR04984
MAR06320
MAR06281
MAR03157
MAR03158
MAR03160
MAR03163
MAR03164
MAR03166
MAR03885
MAR00970
MAR00923
MAR05365
MAR05369
MAR00818
MAR03428
MAR09719
MAR03430
Expected feature/value/output:
At the moment, 5,8,11,14,17-Eicosapentenoyl Coenzyme A (
MAM03284m
) (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA (MAM00103m
) are different metabolites, but the changes proposed in #771 would removeMAM03284m
and replace it withMAM00103m
in all the reactions it currently participates in, so I'm not addressing that further in this issue.I think it's clear that
MAR00970
,MAR03428
,MAR09719
, andMAR03430
are all duplicates of various subsets of the reactions betweenMAR05408
andMAR03885
, so they should all be removed in favor of the more detailed series of reactions.MAR00818
is almost a duplicate ofMAR05365
throughMAR04984
, except it incorrectly ends with octanoyl-CoA instead of 5-octenoyl-CoA (see #765 for a similar set of duplicates), so it should definitely be removed.At first glance,
MAR00923
just looks like an incorrect version ofMAR05370
, but I'm pretty sure it's supposed to represent the following (plausible, if slightly non-canonical) series of reactions:So I don't think
MAR00923
has to be removed, but its GPR should be changed to(ACADL or ACAD9) and (ECI1 or ECI2) and ECH1 and DECR1 and HADHA and HADHB
.MAR05365
represents one full round of beta-oxidation of beta-oxidation from (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA to (4Z,7Z,10Z,13Z)-hexadecatetraenoyl CoA, but the first step in that process would be oxidation by ACADL or ACAD9 to form (2E,6Z,9Z,12Z,15Z)-octadecapentaenoyl-CoA, i.e.MAM03195m
, which is a reactant inMAR05369
, which produces (4Z,7Z,10Z,13Z)-hexadecatetraenoyl CoA. To resolve this partial redundancy, I propose thatMAR05365
be edited to just represent the first step of this round of beta-oxidation, i.e. (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + FAD -> (2E,9Z,12Z,15Z)-octadecapentaenoyl-CoA + FADH2 with a GPR of ACADL or ACAD9.Proposed changes:
MAR00923
to(ENSG00000115361 or ENSG00000177646) and (ENSG00000167969 or ENSG00000198721) and ENSG00000104823 and ENSG00000104325 and ENSG00000084754 and ENSG00000138029
MAR05365
toMAM00108m + MAM01802m -> MAM03195m + MAM01803m
, GPR:ENSG00000115361 or ENSG00000177646
MAR00818
for being inaccurateMAR00970
for being a duplicate ofMAR05408
+MAR05412
+MAR05410
+MAR05403
MAR09719
for being a duplicate ofMAR05365
+MAR05369
+MAR05298
+MAR05312
+MAR05306
+MAR05242
+MAR05177
+MAR05090
+MAR05083
+MAR04978
+MAR05001
+MAR04988
+MAR04984
+MAR06320
+MAR06281
+MAR03157
+MAR03158
+MAR03160
+MAR03163
+MAR03164
+MAR03166
+MAR03885
MAR03248
for being a duplicate ofMAR05376
+MAR05370
+MAR05369
+MAR05298
+MAR05312
+MAR05306
+MAR05242
+MAR05177
+MAR05090
+MAR05083
+MAR04978
+MAR05001
+MAR04988
+MAR04984
+MAR06320
+MAR06281
+MAR03157
+MAR03158
+MAR03160
+MAR03163
+MAR03164
+MAR03166
+MAR03885
MAR03430
for being a duplicate ofMAR05408
+MAR05412
+MAR05410
+MAR05403
+MAR05376
+MAR05370
+MAR05369
+MAR05298
+MAR05312
+MAR05306
+MAR05242
+MAR05177
+MAR05090
+MAR05083
+MAR04978
+MAR05001
+MAR04988
+MAR04984
+MAR06320
+MAR06281
+MAR03157
+MAR03158
+MAR03160
+MAR03163
+MAR03164
+MAR03166
+MAR03885