The eukaryotic alpha-ketoacid dehydrogenase complex family comprises three large, mitochondrial-localized multi-enzyme complexes: pyruvate dehydrogenase, alpha-ketoglutarate (oxoglutarate) dehydrogenase, and the branched-chain alpha-ketoacid dehydrogenase complex. They share the same basic architecture, using multiple copies of three enzymes as major building blocks, referred to as E1, E2 and E3. A dihydrolipoyl transacylase (E2) forms the core of the complex, with an alpha-ketoacid dehydrogenase (E1) and a dihydrolipoamide dehydrogenase (E3) attached to the E2 core through non-covalent bonds. The E3 component (DLD) is the same in each complex. Additional proteins are also present in some systems/complexes, such as a regulatory protein kinase and protein phosphatase. Alpha-ketoacid dehydrogenase multienzyme complexes catalyze analogous reactions in central metabolism. An alpha-ketoacid (pyruvate, branched-chain alpha-ketoacids or alpha-ketoglutarate) is decarboxylated by the E1 component followed by transfer of the remaining acyl group to the lipoamide cofactor bound to E2. Next, the active site of the E2 catalytic domain catalyzes the transfer of the acyl group from lipoamide to coenzyme A (CoA) forming acyl-CoA and leaving the lipoamide in a reduced state. Eventually, the E3 component reactivates the lipoamide by oxidation using a bound FAD cofactor and NAD+ as external electron acceptor, thereby completing the functional cycle. (Adapted from PMID:10745006.)