2-oxoacid dehydrogenase complexes (OADHCs)

The 2-oxoacid dehydrogenase complexes (OADHCs) are a family of high-molecular-weight multienzyme complexes that catalyze the oxidative decarboxylation of 2-oxoacids to their respective acyl-CoA derivatives while reducing NAD+ to NADH. This family includes the pyruvate dehydrogenase complex (PDC), the alpha-ketoglutarate dehydrogenase complex (OGDC), and the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), all of which are central to mitochondrial energy metabolism and the TCA cycle. These complexes are characterized by a conserved structure consisting of three main components: a substrate-specific dehydrogenase (E1), a dihydrolipoyl transacetylase/succinyltransferase (E2), and a dihydrolipoyl dehydrogenase (E3). Dysregulation or deficiency in these complexes is linked to various metabolic disorders, such as lactic acidosis and Maple Syrup Urine Disease, as well as neurodegenerative conditions and cancer. Pharmacological modulation of these complexes, particularly through the inhibition of regulatory kinases like pyruvate dehydrogenase kinase (PDK), is a significant area of therapeutic research for treating metabolic and oncological diseases.

Other names

2-oxoacid dehydrogenase complexesAlpha-keto acid dehydrogenase complexesOADHCLipoic acid-dependent dehydrogenase complexesMultienzyme complexes of the 2-oxoacid dehydrogenase family