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 CO(2) 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).
