Current behavior:
As briefly mentioned in #607, some mitochondrial reactions in Human-GEM are associated with genes that catalyze analogous reactions in peroxisomes and not mitochondria. I found a total of 128 reactions that involve at least one metabolite in [m] and at least one enzyme known to be involved in fatty-acid oxidation in peroxisomes and not mitochondria. Trying to address all of them in a single issue proved to be unwieldy, so I've moved most into separate issues, and have edited this one so it only addresses the acyl-CoA dehydrogenation reactions:
| ID |
Reaction |
Chain Length |
Unsaturated? |
Current GPR |
Proposed New GPR |
MAR01253 |
20-CoA-20-oxo-LTB4 + O2 --> (18E)-20-oxo-20-CoA-LTB4 + H2O2 |
20 |
yes |
ACOX3 or ACOX1 |
ACAD9 or ACADL or ACADVL (ENSG00000072778 or ENSG00000115361 or ENSG00000177646) |
MAR01270 |
10,11-dihydro-LTB4-CoA + O2 --> 5(S),12(R)-dihydroxy-eicosa-2,8-trans-6,14-cis-tetraenoyl-CoA + H2O2 |
20 |
yes |
ACOX3 or ACOX1 |
ACAD9 or ACADL or ACADVL (ENSG00000072778 or ENSG00000115361 or ENSG00000177646) |
MAR03997 |
O2 + Cis-6-Dodecenoyl Coenzyme A --> H2O2 + trans,cis-lauro-2,6-dienoyl-CoA |
12 |
yes |
ACOX1 |
ACADL or ACADVL (ENSG00000072778 or ENSG00000115361) |
MAR03291 |
FADH2 + Trans,Cis-Dodeca-2,5-Dienoyl Coenzyme A <=> (5Z)-dodecenoyl-CoA + FAD |
12 |
yes |
ACADL or ACADM or ACOX1 or ACADSB |
ACADL (ENSG00000115361) |
MAR03163 |
butyryl-CoA + FAD --> crotonyl-CoA + FADH2 |
4 |
no |
ACAD10 or ACADM or ACADS or ACAD8 or ACAD9 or ACADSB or ACAD11 |
ACADS or ACADSB (ENSG00000122971 or ENSG00000196177) (updated in light of #980) |
MAR03212 |
FAD + propanoyl-CoA --> acrylyl-CoA + FADH2 |
3 |
no |
ACAD10 or ACADM or ACADS or ACAD8 or ACAD9 or ACADSB or ACAD11 |
ACADS or ACADSB (ENSG00000122971 or ENSG00000196177) (updated in light of #980) |
Expected behavior:
ACOX1 and ACOX3 catalyze the oxidation of acyl-CoAs into 2-trans-enoyl-CoAs in peroxisomes, so neither of them should be associated with any of these reactions. The enzymes responsible for catalyzing the same reaction in mitochondria are ACADVL, ACADL, ACADM, ACADS, ACADSB, ACAD8, ACAD9, and ACAD11 (see this paper for a general overview of the differences between mitochondrial and peroxisomal beta-oxidation reactions (specifically figure 1)). The ACADs all have different preferences/affinities for acyl-CoAs with different chain lengths, which is why I included a column for the chain length in the above table, and I've tried to ensure my proposed new GPRs reflect these preferences:
Proposed Changes:
Current behavior:
As briefly mentioned in #607, some mitochondrial reactions in Human-GEM are associated with genes that catalyze analogous reactions in peroxisomes and not mitochondria. I found a total of 128 reactions that involve at least one metabolite in [m] and at least one enzyme known to be involved in fatty-acid oxidation in peroxisomes and not mitochondria. Trying to address all of them in a single issue proved to be unwieldy, so I've moved most into separate issues, and have edited this one so it only addresses the acyl-CoA dehydrogenation reactions:
MAR01253ENSG00000072778 or ENSG00000115361 or ENSG00000177646)MAR01270ENSG00000072778 or ENSG00000115361 or ENSG00000177646)MAR03997ENSG00000072778 or ENSG00000115361)MAR03291ENSG00000115361)MAR03163ENSG00000122971 or ENSG00000196177) (updated in light of #980)MAR03212ENSG00000122971 or ENSG00000196177) (updated in light of #980)Expected behavior:
ACOX1 and ACOX3 catalyze the oxidation of acyl-CoAs into 2-trans-enoyl-CoAs in peroxisomes, so neither of them should be associated with any of these reactions. The enzymes responsible for catalyzing the same reaction in mitochondria are ACADVL, ACADL, ACADM, ACADS, ACADSB, ACAD8, ACAD9, and ACAD11 (see this paper for a general overview of the differences between mitochondrial and peroxisomal beta-oxidation reactions (specifically figure 1)). The ACADs all have different preferences/affinities for acyl-CoAs with different chain lengths, which is why I included a column for the chain length in the above table, and I've tried to ensure my proposed new GPRs reflect these preferences:
Proposed Changes:
MAR01253andMAR01270toENSG00000072778 or ENSG00000115361 or ENSG00000177646MAR03997toENSG00000072778 or ENSG00000115361MAR03291toENSG00000115361MAR03163andMAR03212toENSG00000122971 or ENSG00000196177(updated in light of Mistakes GPR rules beta oxidation - ACAD #980)