Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 1.2.1.105 extracted from

  • Gibson, G.E.; Blass, J.P.; Beal, M.F.; Bunik, V.
    The alpha-ketoglutarate-dehydrogenase complex: a mediator between mitochondria and oxidative stress in neurodegeneration (2005), Mol. Neurobiol., 31, 43-63.
    View publication on PubMed

Activating Compound

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

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

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

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

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
Homo sapiens 5739
-
mitochondrion
-
Rattus norvegicus 5739
-
mitochondrion
-
Sus scrofa 5739
-

Metals/Ions

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

Organism UniProt Comment Textmining
Bos taurus
-
-
-
Escherichia coli
-
-
-
Homo sapiens
-
-
-
Mesocricetus auratus
-
-
-
Mus musculus
-
-
-
Rattus norvegicus
-
-
-
Saccharomyces cerevisiae
-
-
-
Sus scrofa
-
-
-

Source Tissue

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 and Products (Substrate)

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

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

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