The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate and CoA into acetyl-CoA and CO2 in the presence of NAD+. Acetyl-CoA then goes into the citric acid cycle where it reacts with oxaloacetate to form citrate. Acetyl-CoA is also used for fatty acid and cholesterol biosynthesis. The reaction of oxidative decarboxylation of pyruvate therefore serves as a critical link between glycolysis and the citric acid cycle and lipid metabolism. In mammalian cells, the pyruvate dehydrogenase complex is located in the mitochondrial matrix . This complex is comprised of three enzymes: pyruvate dehydrogenase , dihydrolipoamide acetyltransferase, and dihydrolipoamide dehydrogenase . Pyruvate dehydrogenase consists of two subunits: ? and ?. This enzyme catalyzes the removal of CO2 from pyruvate. Mutations in the ? subunits of pyruvate dehydrogenase lead to congenital defects that are usually associated with lactic acidosis, neurodegeneration, and early death .~Pyruvate dehydrogenase kinase 1 phosphorylates pyruvate dehydrogenase ?1 subunit at Ser293 to inactivate its activity . This phosphorylation contributes to the tumor metabolic reprogramming toward glycolysis in hypoxia by inhibiting the citric acid cycle .