Category: catabolism
Branch point between glycolytic endpoint and TCA / fermentation / gluconeogenesis. Three fates: (1) pyruvate dehydrogenase (PDH) → acetyl-CoA (mitochondrial, irreversible; the gateway to TCA + fatty acid synthesis); (2) lactate dehydrogenase (LDH) → lactate (cytosolic; regenerates NAD+ in anaerobic conditions or in Warburg-effect tumors; type A tissues = muscle/liver, type B = heart); (3) pyruvate carboxylase → oxaloacetate (anaplerotic; mitochondrial; gluconeogenesis entry). PDH deficiency is the most common congenital lactic acidosis; thiamine deficiency (Wernicke-Korsakoff) presents partly as PDH dysfunction (TPP cofactor). Dichloroacetate (DCA) activates PDH and is investigated for MELAS + congenital lactic acidosis.