Literature summary for 1.2.1.105 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.

Search for more literature for 1.2.1.105

Activating Compound

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

Inhibitors

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

Localization

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

Metals/Ions

Metals/Ions	Comment	Organism	Structure
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)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
2-oxoglutarate + lipoamide	Saccharomyces cerevisiae	-	S-succinyldihydrolipoamide + CO2	-	?
2-oxoglutarate + lipoamide	Homo sapiens	reductions in enzyme activity occurs in a number of neurodegenerative disorders including Alzheimers 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

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Saccharomyces cerevisiae	-	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
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
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

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

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2-oxoglutarate + lipoamide	-	Homo sapiens	S-succinyldihydrolipoamide + CO2	-	?
2-oxoglutarate + lipoamide	-	Saccharomyces cerevisiae	S-succinyldihydrolipoamide + CO2	-	?
2-oxoglutarate + lipoamide	reductions in enzyme activity occurs in a number of neurodegenerative disorders including Alzheimers 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

Cofactor	Comment	Organism	Structure
additional information	EC 1.8.1.4, dihydrolipoyl dehydrogenase component of the 2-oxoglutarate dehydrogenase complex is a flavin protein	Homo sapiens
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
thiamine diphosphate	-	Saccharomyces cerevisiae
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
thiamine diphosphate	required, 2-oxoglutarate dehydrogenase component	Homo sapiens

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Release 2023.1 (January 2023)