Duplicate Pristanoyl-CoA Metabolites

[Devlin-Moyer]

Current behavior:

Pristanoyl-CoA is currently represented by three separate metabolites: MAM00075, MAM00078 and MAM03887. MAM00075 specifically represents the (2R) enantiomer and MAM00078 specifically represents the (2S) enantiomer, while MAM03887 maybe represents a racemic mixture of both. All of the reactions MAM03887 participates in have equivalents that use MAM00075 or MAM00078:

ID	Reaction	Notes
MAR03390	ATP [c] + CoA [c] + pristanic acid [c] --> (2R)-pristanoyl-CoA [c] + AMP [c] + PPi [c]
MAR00739	ATP [c] + CoA [c] + pristanic acid [c] --> Pristanoyl Coenzyme A [c] + AMP [c] + PPi [c]	Could be edited to use MAM00078c
MAR03387	ATP [x] + CoA [x] + pristanic acid [x] --> (2S)-pristanoyl-CoA [x] + AMP [x] + PPi [x]
MAR03493	ATP [x] + CoA [x] + pristanic acid [x] --> (2R)-pristanoyl-CoA [x] + AMP [x] + PPi [x]
MAR05183	ATP [x] + CoA [x] + pristanic acid [x] --> AMP [x] + PPi [x] + Pristanoyl Coenzyme A [x]	Duplicate of MAR03387 and/or MAR03494
MAR01674	H2O [x] + Pristanoyl Coenzyme A [x] --> CoA [x] + H+ [x] + pristanic acid [x]	Doesn't have stereospecific equivalents (yet)
MAR01647	Pristanoyl Coenzyme A [x] ⇔ Pristanoyl Coenzyme A [c]	Less accurate version of MAR01674
MAR06775	ATP [c] + H2O [c] + Pristanoyl Coenzyme A [c] ⇒ ADP [c] + H+ [c] + Pi [c] + Pristanoyl Coenzyme A [x]	Doesn't have stereospecific equivalents (yet)
MAR03498	(2S)-pristanoyl-CoA [x] + FAD [x] --> FADH2 [x] + trans-2,3-dehydropristanoyl-CoA [x]
MAR03501	H2O [x] + trans-2,3-dehydropristanoyl-CoA [x] --> 3-hydroxypristanoyl-CoA [x]
MAR03503	3-hydroxypristanoyl-CoA [x] + NAD+ [x] --> 3-ketopristanoyl-CoA [x] + H+ [x] + NADH [x]
MAR03505	3-ketopristanoyl-CoA [x] + CoA [x] --> 4,8,12-trimethyltridecanoyl-CoA [x] + propanoyl-CoA [x]
MAR05184	CoA [x] + FAD [x] + H2O [x] + NAD+ [x] + Pristanoyl Coenzyme A [x] --> 4,8,12-trimethyltridecanoyl-CoA [x] + FADH2 [x] + H+ [x] + NADH [x] + propanoyl-CoA [x]	Redundant with MAR03498 through MAR03505
MAR03506	4,8,12-trimethyltridecanoyl-CoA [x] + FAD [x] --> (4R,8R,12R)-trimethyl-(2E)-tridecenoyl-CoA + FADH2 [x]
MAR03508	(4R,8R,12R)-trimethyl-(2E)-tridecenoyl-CoA [x] + H2O [x] --> 3(R)-hydroxy-(4R,8R,12R)-trimethyl-tridecanoyl-CoA [x]
MAR03509	3(R)-hydroxy-(4R,8R,12R)-trimethyl-tridecanoyl-CoA [x] + NAD+ [x] --> 3-oxo-(4R,8R,12R)-trimethyl-tridecanoyl-CoA [x] + H+ [x] + NADH [x]
MAR03510	3-oxo-(4R,8R,12R)-trimethyl-tridecanoyl-CoA + CoA --> (2R,6R,10R)-trimethyl-hendecanoyl-CoA + acetyl-CoA
MAR03511	(2R,6R,10R)-trimethyl-hendecanoyl-CoA [x] --> (2S,6R,10R)-trimethyl-hendecanoyl-CoA [x]
MAR03512	(2S,6R,10R)-trimethyl-hendecanoyl-CoA [x] + FAD [x] --> (2S,6R,10R)-trimethyl-(2E)-hendecenoyl-CoA [x] + FADH2 [x]
MAR03513	(2S,6R,10R)-trimethyl-(2E)-hendecenoyl-CoA [x] + H2O [x] --> 3(R)-hydroxy-(2S,6R,10)-trimethyl-hendecanoyl-CoA [x]
MAR03514	3(R)-hydroxy-(2S,6R,10)-trimethyl-hendecanoyl-CoA [x] + NAD+ [x] --> 3-oxo-(2S,6R,10R)-trimethyl-hendecanoyl-CoA [x] + H+ [x] + NADH [x]
MAR03515	3-oxo-(2S,6R,10R)-trimethyl-hendecanoyl-CoA [x] + CoA [x] --> 4(R),8-dimethyl-nonanoyl-CoA [x] + propanoyl-CoA [x]
MAR01600	3 CoA [x] + 2 FAD [x] + 3 H2O [x] + 3 NAD+ [x] + Pristanoyl Coenzyme A [x] --> acetyl-CoA [x] + 2 FADH2 [x] + 5 H+ [x]+ 3 NADH [x] + 2 propanoyl-CoA [x] + 4,8-Dimethylnonanoyl Coenzyme A [x]	Redundant with MAR03506 through MAR03515

MAM03554x and MAM00933x (the products of MAR01600 and MAR03515, respectively) are also duplicate representations of 4,8-dimethylnonanoyl-CoA, but I address that in #777.

Expected behavior:

I think it's unnecessary to have a separate metabolite for racemic/unspecified stereochemistry pristanoyl-CoA, so those metabolites and reactions should either be removed or edited to represent one of the two enantiomers where a stereospecific version doesn't already exist. (2S)-pristanoyl-CoA (MAM00078) only exists in the peroxisome at the moment, so I'm proposing that a new metabolite MAM00078c be created to represent it in the cytosol and replace MAM03887c in MAR00739.

MAR01647 and MAR06775 both represent transport of pristanoyl-CoA from the cytosol into peroxisomes, but only MAR06775 correctly represents that this is an ATP-dependent process mediated by ABCD3 (source). Since they both use the racemic pristanoyl-CoA metabolite (MAM03887), and equivalent reactions using MAM00075 or MAM0078 don't already exist, rather than removing MAR01647 for being a duplicate of MAR06775, I'm proposing to edit both reactions so that they both represent ATP-dependent import, but one uses (2S)-pristanoyl-CoA (MAM00078c) and the other uses (2R)-pristanoyl-CoA (MAM00075c). Also it turns out that ABCD3 probably removes the CoA from its substrates just before it transports them across the peroxisomal membrane (source), so I'm also accounting for that in my proposed changes.

Proposed changes:

• Create a new metabolite MAM00078c to represent cytosolic (2S)-pristanoyl-CoA
• Replace MAM03887c with MAM00078c in MAR00739
• Remove MAR05183 for being a duplicate of MAR03387 and/or MAR03493
• Edit MAR01674 to be MAM00078c + MAM01371c + 2 MAM02040m -> MAM02766x + MAM01597c + MAM02039c, GPR: ENSG00000117528, references: PMID:24333844;PMID:33500543
• Edit MAR06775 to be MAM00075c + MAM01371c + 2 MAM02040m -> MAM00077x + MAM01597c + MAM02039c, GPR: ENSG00000117528, references: PMID:24333844;PMID:33500543
  • Note that MAM00077x was removed in Duplicate IDs for same mets #519, and if these changes are implemented before the ones proposed in Stereochemistry of Phytanic Acid Metabolism #773, it'll have to be resurrected
• Remove MAR05184 for being a duplicate of MAR03498 + MAR03501 + MAR03503 + MAR03505
• Remove MAR01600 for being a duplicate of MAR03506 + MAR03508 + MAR03509 + MAR03510 + MAR03511 + MAR03512 + MAR03513 + MAR03514 + MAR03515
• Remove MAM03887c for being a duplicate of MAM00075c and/or MAM00078c
• Remove MAM03887x for being a duplicate of MAM00075x and/or MAM00078x