The pyruvate dehydrogenase (PDH) complex converts pyruvate into acetyl-CoA when bound to the co-enzyme, thiamine pyrophosphate (TPP). In cancer, phosphorylation of PDH by pyruvate dehydrogenase kinase isoforms 1 to 4 (PDK1 to 4) inactivates PDH, leading to a reduction, in pyruvate conversion to lactate by lactate dehydrogenase A (LDHA). Inhibition of PDK activity by dichloroacetate (DCA) reduces phosphorylation and induces apoptosis. TPP binding to PDH has also been suggested to inhibit PDK phosphorylation and may explain why high dose thiamine has anti-proliferative effects in a tumor xenograft model. In the oxidative direction, pyruvate is converted to acetyl-CoA by PDH and is continually catabolized to α- ketoglutarate. The thiamine-dependent enzyme alpha-ketoglutarate dehydrogenase (α- KGDH) converts α- ketoglutarate to succinyl-CoA. Cancer cells exploit glutaminolysis to resupply the tricarboxylic acid (TCA) cycle with carbon as α- ketoglutarate. Continuation of the TCA cycle results in anabolic activity to provide precursors for nucleotides, amino acids, and lipids for biomass generation.