Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (By similarity). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (By similarity). 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 (By similarity). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity). (R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + NAD(+) = (R)-N(6)-lipoyl-L-lysyl-[protein] + H(+) + NADH Binds 1 FAD per subunit. Homodimer. Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDHA (PDHA1 or PDHA2) and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (by non covalent bonds). The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3). It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A. Interacts with PDHX. Mainly localizes in the mitochondrion. A small fraction localizes to the nucleus, where the 2-oxoglutarate dehydrogenase complex is required for histone succinylation. Expressed in heart (at protein level). Tyrosine phosphorylated. The active site is a redox-active disulfide bond. Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.