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SysBioChalmers / Human-GEM

The generic genome-scale metabolic model of Homo sapiens
https://sysbiochalmers.github.io/Human-GEM-guide/
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Duplicate Beta-Oxidation Reactions for Pristanoyl-CoA #777

Open Devlin-Moyer opened 11 months ago

Devlin-Moyer commented 11 months ago

Some of these changes depend on the ones proposed in #776

Current behavior:

There are two parallel pathways representing the peroxisomal beta-oxidation of 4,8,12-trimethyltridecanoyl-CoA to 4,8-dimethylnonanoyl-CoA:

ID Reaction Notes
MAR03506 4,8,12-trimethyltridecanoyl-CoA [x] + FAD [x] --> (4R,8R,12R)-trimethyl-(2E)-tridecenoyl-CoA [x] + 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 [x] + CoA [x] --> (2R,6R,10R)-trimethyl-hendecanoyl-CoA [x] + acetyl-CoA [x]
MAR05108 4,8,12-trimethyltridecanoyl-CoA [x] + CoA [x] + FAD [x] + H2O [x] + NAD+ [x] --> acetyl-CoA [x] + FADH2 [x] + H+ [x] + NADH [x] + 2,6,10-Trimethyl Undecanoyl Coenzyme A [x] Redundant with MAR03506 through MAR03510
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]
MAR05028 CoA [x] + FAD [x] + H2O [x] + NAD+ [x] + 2,6,10-Trimethyl Undecanoyl Coenzyme A [x] --> FADH2 [x] + H+ [x] + NADH [x] + propanoyl-CoA [x] + 4,8-Dimethylnonanoyl Coenzyme A [x] Redundant with MAR03511 through MAR03515
MAR00139 L-carnitine [x] + 4,8-Dimethylnonanoyl Coenzyme A [x] <=> 4,8-dimethylnonanoylcarnitine [x] + CoA [x] Should only have CROT in its GPR, not also CRAT (sources: 1, 2)
MAR04782 4,8-dimethylnonanoylcarnitine [x] <=> 4,8-dimethylnonanoylcarnitine [c] Should not be associated with SLC25A20
MAR03521 4(R),8-dimethyl-nonanoyl-CoA [c] + L-carnitine [c] <=> 4,8-dimethylnonanoylcarnitine [c] + CoA [c]
MAR03517 4(R),8-dimethyl-nonanoyl-CoA [c] <=> 4(R),8-dimethyl-nonanoyl-CoA [x] Less realistic version of MAR00139 + MAR04782 + MAR03521 (source)
MAR03520 4,8-dimethylnonanoylcarnitine [c] + L-carnitine [m] <=> 4,8-dimethylnonanoylcarnitine [m] + L-carnitine [c] GPR should be SLC25A20 (currently empty)
MAR00315 4,8-dimethylnonanoylcarnitine [c] <=> 4,8-dimethylnonanoylcarnitine [m] Less accurate version of MAR03520
MAR00138 4,8-dimethylnonanoylcarnitine [x] <=> 4,8-dimethylnonanoylcarnitine [m] Duplicate of MAR00139 + MAR00315

I know that removing SLC25A20 from the GPR of MAR04782 would leave it without a GPR, but as far as I can tell, people are confident that SLC25A20 is not in peroxisomal membranes, and some other as yet unidentified protein is responsible for transporting acylcarnitines out of peroxisomes (see e.g. this paper).

Proposed changes: