A three-carbon intermediate (2-oxopropanoate) important in glucose metabolism and amino acid synthesis. Pyruvate produced in glycolysis (the Embden–Meyerhof pathway) feeds into the (tricarboxylic acid cycle). Pyruvate carboxylase (EC 220.127.116.11) catalyses the formation of four-carbon oxaloacetate from pyruvate, CO2, and ATP in gluconeogenesis whereas pyruvate dehydrogenase (PDH, EC 18.104.22.168) uses pyruvate to produce acetyl-CoA. Pyruvate carboxylase is a key regulatory enzyme in gluconeogenesis, lipogenesis, and neurotransmitter synthesis. Defects in the pyruvate dehydrogenase complex are a common cause of primary lactic acidosis in children, which can cause mental retardation and death, and can arise through mutations in either the gene for pyruvate decarboxylase or the gene encoding the E1α polypeptide of the pyruvate dehydrogenase (EC 22.214.171.124) complex. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK, EC 126.96.36.199) results in inactivation and is an important control in energy metabolism. There are multiple tissue-specific PDK isozymes. Pyruvate dehydrogenase phosphatase deficiency can also lead to lactic acidosis.
Subjects: Medicine and Health.