Pyruvate Dehydrogenase (PDH)

Pyruvate dehydrogenase (PDH) is a key enzyme that catalyzes the conversion of pyruvate, the end product of glycolysis, into acetyl-CoA, which then enters the tricarboxylic acid (TCA) cycle. This reaction also produces carbon dioxide (CO₂) and reduces NAD⁺ to NADH. The PDH reaction serves as a critical link between glycolysis and aerobic respiration. The PDH is not a single protein but is part of a large multi-enzyme complex called the pyruvate dehydrogenase complex (PDC). PDHC acts as a gatekeeper for carbohydrate entry into mitochondrial metabolism—its activity determines whether glucose-derived carbons enter oxidative phosphorylation or alternative pathways like lactate production under hypoxia or in cancer cells. Dysregulation has been implicated in metabolic diseases, and mutations can cause neurological disorders due to impaired energy metabolism in neurons.

Inhibition of Pyruvate Dehydrogenase Kinase (PDK)