FUNCTION 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) (PubMed:15712224, PubMed:16442803, PubMed:16770810, PubMed:17404228, PubMed:20160912, PubMed:20385101). The 2-oxoglutarate dehydrogenase complex is 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). 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).CATALYTIC ACTIVITY N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + NAD(+) = N(6)-[(R)-lipoyl]-L-lysyl-[protein] + NADH + H(+)COFACTOR Binds 1 FAD per subunit.ACTIVITY REGULATION Disruption of native heterodimer state inhibits primary dihydrolipoamide dehydrogenase activity and induces serine protease activity.SUBUNIT Homodimer (PubMed:15946682). 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) (PubMed:14638692). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (by non covalent bonds) (PubMed:14638692, PubMed:20361979). The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2), DLD (dihydrolipoamide dehydrogenase; E3) and the assembly factor KGD4 (By similarity). It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A (PubMed:29211711). Interacts with PDHX (PubMed:16442803, PubMed:20160912, PubMed:20361979, PubMed:20385101).INTERACTION Mainly localizes in the mitochondrion. A small fraction localizes to the nucleus, where the 2-oxoglutarate dehydrogenase complex is required for histone succinylation.ALTERNATIVE PRODUCTS Tyrosine phosphorylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS The active site is a redox-active disulfide bond.SIMILARITY Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.SEQUENCE CAUTION Extended N-terminus.