OGDH

This gene encodes one subunit of the 2-oxoglutarate dehydrogenase complex. This complex catalyzes the overall conversion of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO(2) during the Krebs cycle. The protein is located in the mitochondrial matrix and uses thiamine pyrophosphate as a cofactor. A congenital deficiency in 2-oxoglutarate dehydrogenase activity is believed to lead to hypotonia, metabolic acidosis, and hyperlactatemia. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

Full Name

Oxoglutarate Dehydrogenase

Function

2-oxoglutarate dehydrogenase (E1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHC) (PubMed:24495017, PubMed:25210035, PubMed:28435050).
Participates in the first step, rate limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA and CO2 catalyzed by the whole OGDHC (PubMed:24495017, PubMed:25210035, PubMed:28435050).
Catalyzes the irreversible decarboxylation of 2-oxoglutarate (alpha-ketoglutarate) via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST) (PubMed:24495017, PubMed:25210035, PubMed:28435050).
Plays a key role in the Krebs (citric acid) cycle, which is a common pathway for oxidation of fuel molecules, including carbohydrates, fatty acids, and amino acids (PubMed:25210035).
Can catalyze the decarboxylation of 2-oxoadipate in vitro, but at a much lower rate than 2-oxoglutarate (PubMed:28435050).
Mainly active in the mitochondrion (PubMed:29211711).
A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711).

Biological Process

2-oxoglutarate metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Cerebellar cortex developmentIEA:Ensembl
Generation of precursor metabolites and energyISS:UniProtKB
Glycolytic processIEA:UniProtKB-KW
Hippocampus developmentIEA:Ensembl
Histone succinylationManual Assertion Based On ExperimentIDA:UniProtKB
NADH metabolic processIEA:Ensembl
Olfactory bulb mitral cell layer developmentIEA:Ensembl
Pyramidal neuron developmentIEA:Ensembl
Striatum developmentIEA:Ensembl
Succinyl-CoA metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Tangential migration from the subventricular zone to the olfactory bulbIEA:Ensembl
Thalamus developmentIEA:Ensembl
Tricarboxylic acid cycleManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Mitochondrion
Nucleus
Mainly localizes in the mitochondrion. A small fraction localizes to the nucleus, where the 2-oxoglutarate dehydrogenase complex is required for histone succinylation.