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Literature summary extracted from

  • Gibson, G.E.; Park, L.C.H.; Sheu, K.F.R.; Blass, J.P.; Calingasan, N.Y.
    The alpha-ketoglutarate dehydrogenase complex in neurodegeneration (2000), Neurochem. Int., 36, 97-112.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.2.1.105 ADP stimulates Homo sapiens
1.2.1.105 ADP stimulates Saccharomyces cerevisiae
1.2.1.105 NAD+ stimulates Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.2.1.105 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
 Homo sapiens
1.2.1.105 1-methyl-4-phenylpyridinium
-
 Homo sapiens
1.2.1.105 ATP
-
 Homo sapiens
1.2.1.105 Ca2+ 0.01 mM, decreases the concentration of 2-oxoglutarate required for half-maximal activity, inhibition at higher concentrations Homo sapiens
1.2.1.105 NADH
-
 Homo sapiens
1.2.1.105 NH4+
-
 Homo sapiens
1.2.1.105 Valproic acid
-
 Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.2.1.105 mitochondrion
-
 Homo sapiens 5739
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.2.1.105 Ca2+ 0.01 mM, decreases the concentration of 2-oxoglutarate required for half-maximal activity, inhibition at higher concentrations Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.2.1.105 2-oxoglutarate + lipoamide Saccharomyces cerevisiae
-
 S-succinyldihydrolipoamide + CO2
-
 ?
1.2.1.105 2-oxoglutarate + lipoamide Homo sapiens reductions in enzyme activity occurs in a number of neurodegenerative disorders including Alzheimer‘s disease. The reduction in 2-oxoglutarate dehydrogenase complex activity can be linked to several aspects of brain dysfunction and neuropathology in a number of neurodegenerative diseases S-succinyldihydrolipoamide + CO2
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.2.1.105 Homo sapiens
-
-
-
1.2.1.105 Saccharomyces cerevisiae
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.2.1.105 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2 the enzyme complex catalyzes the reaction : 2-oxoglutarate + CoA + NAD+--> succinyl-CoA + CO2 + NADH, the following partial reactions are catalyzed: 1. HOOC(CH2)2COCOOH + (thiamine diphosphate)-E1--> (HOOC(CH2)2 CHOH-thiamine-diphosphate)-E1 + CO2, 2. (HOOC(CH2)2CH OH-thiamine-diphosphate)-E1 + (LipS2)-E2--> (HOOC(CH)2 CO-(SLipSH))-E2 + (thiamine-diphosphate)-E1, 3. (HOOC(CH2)2CO-(SLipSH))-E2 + HSCoA--> (Lip(SH)2)-E2 + HOOC(CH2)2CO-SCoA, 4. (Lip(SH)2)-E2 + E3-FAD--> (LipS2)-E2 + reduced E3-FAD, 5. reduced E3-FAD + NAD+--> E3-FAD + NADH Homo sapiens
a
1.2.1.105 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2 the enzyme complex catalyzes the reaction : 2-oxoglutarate + CoA + NAD+--> succinyl-CoA + CO2 + NADH, the following partial reactions are catalyzed: 1. HOOC(CH2)2COCOOH + (thiamine diphosphate)-E1--> (HOOC(CH2)2 CHOH-thiamine-diphosphate)-E1 + CO2, 2. (HOOC(CH2)2CH OH-thiamine-diphosphate)-E1 + (LipS2)-E2--> (HOOC(CH)2 CO-(SLipSH))-E2 + (thiamine-diphosphate)-E1, 3. (HOOC(CH2)2CO-(SLipSH))-E2 + HSCoA--> (Lip(SH)2)-E2 + HOOC(CH2)2CO-SCoA, 4. (Lip(SH)2)-E2 + E3-FAD--> (LipS2)-E2 + reduced E3-FAD, 5. reduced E3-FAD + NAD+--> E3-FAD + NADH Saccharomyces cerevisiae
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.2.1.105 brain endothelial cells have about six times higher activity than do brain microglial cells or neurons Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.2.1.105 2-oxoglutarate + lipoamide
-
 Homo sapiens S-succinyldihydrolipoamide + CO2
-
 ?
1.2.1.105 2-oxoglutarate + lipoamide
-
 Saccharomyces cerevisiae S-succinyldihydrolipoamide + CO2
-
 ?
1.2.1.105 2-oxoglutarate + lipoamide reductions in enzyme activity occurs in a number of neurodegenerative disorders including Alzheimer‘s disease. The reduction in 2-oxoglutarate dehydrogenase complex activity can be linked to several aspects of brain dysfunction and neuropathology in a number of neurodegenerative diseases Homo sapiens S-succinyldihydrolipoamide + CO2
-
 ?

Cofactor

EC Number Cofactor Comment Organism Structure
1.2.1.105 additional information EC 1.8.1.4, dihydrolipoyl dehydrogenase component of the 2-oxoglutarate dehydrogenase complex is a flavin protein Homo sapiens
1.2.1.105 additional information EC 2.3.1.61, dihydrolipoamide succinyltransferase component of the 2-oxoglutarate dehydrogenase enzyme complex contains a lipoate moiety that is covalently bound to Lys110 through an epsilon-amide linkage. The thiamine diphosphate reaction adduct then reductively acylates the lipoyl moiety of EC 2.3.1.61 Homo sapiens
1.2.1.105 thiamine diphosphate
-
 Saccharomyces cerevisiae
1.2.1.105 thiamine diphosphate 2-oxoglotarate dehydrogenase component of the 2-oxoglutarate dehydrogenase complex is dependent on thiamine diphosphate. Thiamine diphosphate attacks the alpha-carbon of 2-oxoglutarate and decarboxylates the substrate. The thiamine diphosphate reaction adduct then reductively acylates the lipoyl moiety of EC 2.3.1.61 Homo sapiens
1.2.1.105 thiamine diphosphate required, 2-oxoglutarate dehydrogenase component Homo sapiens