Activating Compound | Comment | Organism | Structure |
---|---|---|---|
thiamine | can reverse the loss in KGDHC in Alzheimer's disease patients | Homo sapiens | |
Trolox | can dramatically increase KGDHC in cultured cells | Homo sapiens |
Application | Comment | Organism |
---|---|---|
medicine | KGDHC is diminished in brains from patients with Alzheimers's disease, Parkinson's disease, Huntington's disease, Wernicke-Korskoff disease, and progressive supranuclear palsy, not diminished in brains of patients that died with schizophrenia, reduced KDGDHC may be a better indicator of the primary reactive oxygen species action than commonly used measures of oxidative stress | Homo sapiens |
medicine | loss of KGDHC activity resulting from the lack of thiamine diphosphate coenzyme may lead to oxidative stress and to neuronal death both directly and by predisposing to other insults | Rattus norvegicus |
additional information | alpha-ketoglutarate-involving reactions belong to the backbone of high-flux reactions, which is rather conserved in evolution | Escherichia coli |
Protein Variants | Comment | Organism |
---|---|---|
additional information | patients bearing the APP670/671 mutation show declined KGDHC activity | Homo sapiens |
additional information | thiamine diphosphate deficiency diminishes KGDHC activity, knockouts of eNOS or ICAM-1 diminish oxidative stress and reduce neuronal death in thiamine-deficient mice, knockouts of E3 have diminished KGDHC in brain and liver | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(R)-2-amino-3-((1,1,2,2-tetrafluoroethyl)thio)propanoic acid | inactivates | Homo sapiens | |
1-methyl-4-phenylpyridine | i.e. MPP+ | Homo sapiens | |
3-nitropropionic acid | - |
Homo sapiens | |
3-NP | - |
Mus musculus | |
amyloid-beta peptide | - |
Homo sapiens | |
H2O2 | addition outside of cells reduces KGDHC activity in proportion to the increase in reactive oxygen species | Homo sapiens | |
H2O2 | oxidative damage to KGDHC | Saccharomyces cerevisiae | |
HNE | - |
Homo sapiens | |
isoquinoline derivative | - |
Homo sapiens | |
KMV | severely inhibits KGDHC activity | Mus musculus | |
KMV | inhibits KGDHC in PC-12 cells and does not alter mitochondrial membrane potential, but is associated with the release of cytochrome-c from mitochondria into the cytosol, reduction in basal cytosolic Ca2+, and diminishing endoplasmic reticulum calcium stores | Rattus norvegicus | |
NADH | allosteric inhibitor, inhibition relieved by micromolar Ca2+ and ADP | Bos taurus | |
reactive oxygen species | - |
Mesocricetus auratus | |
reactive oxygen species | - |
Mus musculus | |
tryptamine-4,5-dione | strongly inhibits | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrion | - |
Homo sapiens | 5739 | - |
mitochondrion | - |
Rattus norvegicus | 5739 | - |
mitochondrion | - |
Sus scrofa | 5739 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
ADP | activates through allosteric binding | Bos taurus | |
Ca2+ | dependent on | Sus scrofa | |
Ca2+ | dependent on, activates through allosteric binding | Bos taurus |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Bos taurus | - |
- |
- |
Escherichia coli | - |
- |
- |
Homo sapiens | - |
- |
- |
Mesocricetus auratus | - |
- |
- |
Mus musculus | - |
- |
- |
Rattus norvegicus | - |
- |
- |
Saccharomyces cerevisiae | - |
- |
- |
Sus scrofa | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Mus musculus | - |
brain | - |
Rattus norvegicus | - |
brain | diminished activities in regions with severe pathology, as well as in areas of minimal pathology, activity declines with the severity of disease | Homo sapiens | - |
cerebellum | - |
Homo sapiens | - |
heart | - |
Sus scrofa | - |
kidney | - |
Bos taurus | - |
liver | - |
Mus musculus | - |
additional information | N2a cells | Mus musculus | - |
ovary | - |
Mesocricetus auratus | - |
PC-12 cell | - |
Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine | - |
Bos taurus | [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2 | - |
? | |
2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine | reaction significant for energy production, neurotransmitter metabolism, and metabolic interaction between mitochondria and cytoplasm | Escherichia coli | [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
alpha-ketoglutarate dehydrogenase | - |
Mus musculus |
alpha-ketoglutarate dehydrogenase | - |
Homo sapiens |
alpha-ketoglutarate dehydrogenase | - |
Rattus norvegicus |
alpha-ketoglutarate dehydrogenase | - |
Saccharomyces cerevisiae |
alpha-ketoglutarate dehydrogenase | - |
Bos taurus |
alpha-ketoglutarate dehydrogenase | - |
Mesocricetus auratus |
alpha-ketoglutarate dehydrogenase complex | - |
Mus musculus |
alpha-ketoglutarate dehydrogenase complex | - |
Escherichia coli |
alpha-ketoglutarate dehydrogenase complex | - |
Homo sapiens |
alpha-ketoglutarate dehydrogenase complex | - |
Rattus norvegicus |
alpha-ketoglutarate dehydrogenase complex | - |
Sus scrofa |
alpha-ketoglutarate dehydrogenase complex | - |
Saccharomyces cerevisiae |
alpha-ketoglutarate dehydrogenase complex | - |
Bos taurus |
alpha-ketoglutarate dehydrogenase complex | - |
Mesocricetus auratus |
E1k | - |
Mus musculus |
E1k | - |
Homo sapiens |
E1k | - |
Rattus norvegicus |
E1k | - |
Saccharomyces cerevisiae |
E1k | - |
Bos taurus |
E1k | - |
Mesocricetus auratus |
KGDHC | - |
Mus musculus |
KGDHC | - |
Escherichia coli |
KGDHC | - |
Homo sapiens |
KGDHC | - |
Rattus norvegicus |
KGDHC | - |
Sus scrofa |
KGDHC | - |
Saccharomyces cerevisiae |
KGDHC | - |
Bos taurus |
KGDHC | - |
Mesocricetus auratus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
lipoic acid | increases KGDHC activity in aged rates | Rattus norvegicus | |
lipoic acid | leads to a stabilization of cognitive functions in Alzheimer's disease patients | Homo sapiens | |
thiamine diphosphate | - |
Rattus norvegicus |