Mitochondrial lipoamide-containing enzymes

Mitochondrial lipoamide-containing enzymes are a group of multienzyme complexes essential for aerobic metabolism and energy production (UniProt: P10515). This group primarily includes the pyruvate dehydrogenase complex (PDC), alpha-ketoglutarate dehydrogenase complex (OGDC), branched-chain alpha-keto acid dehydrogenase complex (BCKDC), and the glycine cleavage system (PubChem: CID 864). These enzymes share a common mechanism involving the covalent attachment of a lipoic acid cofactor to a lysine residue on the E2 subunit or H-protein, facilitating the transfer of acyl groups and electrons (DrugBank: DB00166). In clinical medicine, these enzymes are significant targets of heavy metal toxicity, particularly arsenic, which binds to the dihydrolipoamide intermediate and halts the tricarboxylic acid cycle (NCBI: PMC2756298). Conversely, alpha-lipoic acid is administered therapeutically to support these enzymes in conditions like diabetic neuropathy or certain metabolic disorders (StatPearls: NBK541073). Dysfunction in these complexes is linked to various pathologies, including lactic acidosis, maple syrup urine disease, and primary biliary cholangitis, where they serve as major autoantigens (PubMed: 10648265). The inhibition of these enzymes leads to a failure of cellular respiration and the accumulation of toxic metabolic intermediates.

Other names

Other mitochondrial lipoamide-containing enzymes2-oxoacid dehydrogenase complexesLipoylated enzymesAlpha-keto acid dehydrogenase complexesLipoamide-containing enzymes

These enzymes utilize a lipoamide cofactor to catalyze the oxidative decarboxylation of alpha-keto acids. Drugs like arsenic inhibit these enzymes by binding to the dithiol groups of the lipoamide, while alpha-lipoic acid serves as a therapeutic cofactor or antioxidant (DrugBank: DB00166; NCBI: PMC2756298).