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In #524, when resolving the duplicate representations of the pyruvate dehydrogenase (PDH) and 2-oxoglutarate dehydrogenase (OGDH) complexes, we decided to keep the sets of reactions that explicitly show the involvement of thiamine in the catalytic mechanism (see this comment in particular for the rationale). The reactions representing the catalytic activities of the 2-oxoadipate dehydrogenase (OADH) and branched-chain ketoacid dehydrogenase (BCKDH) complexes do not show the involvement of thiamine, despite the fact that all four complexes use thiamine in exactly the same way (sources for BCKDH and OADH):
Complex
ID
Reaction
Genes
PDH
MAR08746
H+ + pyruvate + thiamin-PP --> 2-(alpha-hydroxyethyl)thiamine-diphosphate + CO2
CoA + S-succinyldihydrolipoamide <=> dihydrolipoamide + succinyl-CoA
DLST
OGDH
MAR06409
H+ + lipoamide + NADH <=> dihydrolipoamide + NAD+
DLD
OADH
MAR04599
2-oxoadipate + H+ + lipoamide --> CO2 + S-glutaryldihydrolipoamide
(OGDH and DLST) or (DHTKD1 and DLST)
OADH
MAR06415
CoA + S-glutaryldihydrolipoamide --> dihydrolipoamide + glutaryl-CoA
DLST
OADH
MAR06409
H+ + lipoamide + NADH <=> dihydrolipoamide + NAD+
DLD
BCKDH
MAR06416
3-methyl-2-oxobutyrate + H+ + lipoamide --> CO2 + S-(2-methylpropanoyl)-dihydrolipoamide
BCKDHB and TMEM91 and BCKDHA
BCKDH
MAR06417
CoA + S-(2-methylpropanoyl)-dihydrolipoamide <=> dihydrolipoamide + isobutyryl-CoA
DBT
BCKDH
MAR06409
H+ + lipoamide + NADH <=> dihydrolipoamide + NAD+
DLD
BCKDH
MAR06419
2-oxo-3-methylvalerate + H+ + lipoamide --> CO2 + S-(2-methylbutanoyl)-dihydrolipoamide
BCKDHB and TMEM91 and BCKDHA
BCKDH
MAR06420
CoA + S-(2-methylbutanoyl)-dihydrolipoamide --> 2-methylbutyryl-CoA + dihydrolipoamide
DBT
BCKDH
MAR06409
H+ + lipoamide + NADH <=> dihydrolipoamide + NAD+
DLD
BCKDH
MAR06421
4-methyl-2-oxopentanoate + H+ + lipoamide --> CO2 + S-(3-methylbutanoyl)-dihydrolipoamide
BCKDHB and TMEM91 and BCKDHA
BCKDH
MAR06422
CoA + S-(3-methylbutanoyl)-dihydrolipoamide --> dihydrolipoamide + isovaleryl-CoA
DBT
BCKDH
MAR06409
H+ + lipoamide + NADH <=> dihydrolipoamide + NAD+
DLD
BCKDH
MAR03800
2-oxobutyrate + CoA + NAD+ --> CO2 + NADH + propanoyl-CoA
BCKDHB and DLD and DBT and BCKDHA
(MAR06409 appears multiple times because DLD is a subunit of all of these complexes; see #529)
Expected feature/value/output:
All reactions representing the activities of 2-ketoacid dehydrogenase complexes should represent the role of thiamine in the catalytic mechanism in the same way. This would entail adding several new reactions to parallel MAR08746 and MAR04209 for the OADH and BCKDH reactions. MAR03800 glosses over the role of lipoic acid in the catalytic mechanism of BCKDH, so I'm also proposing changes to take care of that inconsistency.
Proposed Changes:
Create a new metabolite to represent 2-(4-carboxy-1-hydroxybutyl)thiamine diphosphate
Create a new reaction: 2-oxoadipate (MAM00670m) + thiamin-PP (MAM02984m) + H+ (MAM02039m) -> 2-(4-carboxy-1-hydroxybutyl)thiamine diphosphate + CO2 (MAM01596m), GPR: OGDH or DHTKD1 (ENSG00000105953 or ENSG00000181192)
Replace 2-oxoadipate (MAM00670m) with 2-(4-carboxy-1-hydroxybutyl)thiamine diphosphate, replace CO2 (MAM01596m) with thiamin-PP (MAM02984m), and remove H+ in MAR04599
Create a new metabolite to represent 2-(2-methyl-1-hydroxypropyl)thiamine diphosphate
Create a new reaction: 3-methyl-2-oxobutyrate (MAM00824m) + thiamin-PP (MAM02984m) + H+ (MAM02039m) -> 2-(2-methyl-1-hydroxypropyl)thiamine diphosphate + CO2 (MAM01596m), GPR: BCKDHA and BCKDHB (ENSG00000248098 and ENSG00000083123)
Replace 3-methyl-2-oxobutyrate (MAM00824m) with 2-(2-methyl-1-hydroxypropyl)thiamine diphosphate, replace CO2 (MAM01596m) with thiamin-PP (MAM02984m), and remove H+ in MAR06416
Create a new metabolite to represent 2-(2-methyl-1-hydroxybutyl)thiamine diphosphate
Create a new reaction: 2-oxo-3-methylvalerate (MAM00669m) + thiamin-PP (MAM02984m) + H+ (MAM02039m) -> 2-(2-methyl-1-hydroxybutyl)thiamine diphosphate + CO2 (MAM01596m), GPR: BCKDHA and BCKDHB (ENSG00000248098 and ENSG00000083123)
Replace 2-oxo-3-methylvalerate (MAM00669m) with 2-(2-methyl-1-hydroxybutyl)thiamine diphosphate, replace CO2 (MAM01596m) with thiamin-PP (MAM02984m), and remove H+ in MAR06419
Create a new metabolite to represent 2-(3-methyl-1-hydroxybutyl)thiamine diphosphate
Create a new reaction: 4-methyl-2-oxo-pentanoate (MAM01013m) + thiamin-PP (MAM02984m) + H+ (MAM02039m) -> 2-(3-methyl-1-hydroxybutyl)thiamine diphosphate + CO2 (MAM01596m), GPR: BCKDHA and BCKDHB (ENSG00000248098 and ENSG00000083123)
Replace 4-methyl-2-oxo-pentanoate (MAM01013m) with 2-(3-methyl-1-hydroxybutyl)thiamine diphosphate, replace CO2 (MAM01596m) with thiamin-PP (MAM02984m), and remove H+ in MAR06421
Create a new metabolite to represent 2-(1-hydroxypropyl)thiamine diphosphate
Create a new metabolite to represent S-propanoyldihydrolipoamide
Change MAR03800 to: 2-oxobutyrate (MAM00671m) + thiamin-PP (MAM02984m) + H+ (MAM02039m) -> 2-(1-hydroxypropyl)thiamine diphosphate + CO2 (MAM01596m), GPR: BCKDHA and BCKDHB (ENSG00000248098 and ENSG00000083123)
Create a new reaction: 2-(1-hydroxypropyl)thiamine diphosphate + lipoamide (MAM02393m) -> S-propanoyldihydrolipoamide + thiamin-PP (MAM02984m), GPR: BCKDHA and BCKDHB and DBT (ENSG00000248098 and ENSG00000083123 and ENSG00000137992)
Create a new reaction: S-propanoyldihydrolipoamide + CoA (MAM01597m) -> propanoyl-CoA (MAM02774m) + dihydrolipoamide (MAM01701m), GPR: DBT (ENSG00000137992)
The text was updated successfully, but these errors were encountered:
Current behavior:
In #524, when resolving the duplicate representations of the pyruvate dehydrogenase (PDH) and 2-oxoglutarate dehydrogenase (OGDH) complexes, we decided to keep the sets of reactions that explicitly show the involvement of thiamine in the catalytic mechanism (see this comment in particular for the rationale). The reactions representing the catalytic activities of the 2-oxoadipate dehydrogenase (OADH) and branched-chain ketoacid dehydrogenase (BCKDH) complexes do not show the involvement of thiamine, despite the fact that all four complexes use thiamine in exactly the same way (sources for BCKDH and OADH):
(
MAR06409
appears multiple times because DLD is a subunit of all of these complexes; see #529)Expected feature/value/output:
All reactions representing the activities of 2-ketoacid dehydrogenase complexes should represent the role of thiamine in the catalytic mechanism in the same way. This would entail adding several new reactions to parallel
MAR08746
andMAR04209
for the OADH and BCKDH reactions.MAR03800
glosses over the role of lipoic acid in the catalytic mechanism of BCKDH, so I'm also proposing changes to take care of that inconsistency.Proposed Changes:
MAM00670m
) + thiamin-PP (MAM02984m
) + H+ (MAM02039m
) -> 2-(4-carboxy-1-hydroxybutyl)thiamine diphosphate + CO2 (MAM01596m
), GPR: OGDH or DHTKD1 (ENSG00000105953 or ENSG00000181192
)MAM00670m
) with 2-(4-carboxy-1-hydroxybutyl)thiamine diphosphate, replace CO2 (MAM01596m
) with thiamin-PP (MAM02984m
), and remove H+ inMAR04599
MAM00824m
) + thiamin-PP (MAM02984m
) + H+ (MAM02039m
) -> 2-(2-methyl-1-hydroxypropyl)thiamine diphosphate + CO2 (MAM01596m
), GPR: BCKDHA and BCKDHB (ENSG00000248098 and ENSG00000083123
)MAM00824m
) with 2-(2-methyl-1-hydroxypropyl)thiamine diphosphate, replace CO2 (MAM01596m
) with thiamin-PP (MAM02984m
), and remove H+ inMAR06416
MAM00669m
) + thiamin-PP (MAM02984m
) + H+ (MAM02039m
) -> 2-(2-methyl-1-hydroxybutyl)thiamine diphosphate + CO2 (MAM01596m
), GPR: BCKDHA and BCKDHB (ENSG00000248098 and ENSG00000083123
)MAM00669m
) with 2-(2-methyl-1-hydroxybutyl)thiamine diphosphate, replace CO2 (MAM01596m
) with thiamin-PP (MAM02984m
), and remove H+ inMAR06419
MAM01013m
) + thiamin-PP (MAM02984m
) + H+ (MAM02039m
) -> 2-(3-methyl-1-hydroxybutyl)thiamine diphosphate + CO2 (MAM01596m
), GPR: BCKDHA and BCKDHB (ENSG00000248098 and ENSG00000083123
)MAM01013m
) with 2-(3-methyl-1-hydroxybutyl)thiamine diphosphate, replace CO2 (MAM01596m
) with thiamin-PP (MAM02984m
), and remove H+ inMAR06421
MAR03800
to: 2-oxobutyrate (MAM00671m
) + thiamin-PP (MAM02984m
) + H+ (MAM02039m
) -> 2-(1-hydroxypropyl)thiamine diphosphate + CO2 (MAM01596m
), GPR: BCKDHA and BCKDHB (ENSG00000248098 and ENSG00000083123
)MAM02393m
) -> S-propanoyldihydrolipoamide + thiamin-PP (MAM02984m
), GPR: BCKDHA and BCKDHB and DBT (ENSG00000248098 and ENSG00000083123 and ENSG00000137992
)MAM01597m
) -> propanoyl-CoA (MAM02774m
) + dihydrolipoamide (MAM01701m
), GPR: DBT (ENSG00000137992
)The text was updated successfully, but these errors were encountered: