Pyruvate Carboxylase

Pyruvate Carboxylase (PC) is an enzyme of the ligase class that catalyzes (depending on the species) the physiologically irreversible carboxylation of pyruvate to form oxaloacetate (OAA). The reaction it catalyzes is: pyruvate + HCO−3 + ATP → oxaloacetate + ADP + P. It is an important anaplerotic reaction that creates oxaloacetate from pyruvate. The enzyme is a mitochondrial protein containing a biotin prosthetic group, requiring magnesium or manganese and acetyl CoA. Pyruvate carboxylase was first discovered in 1959 at Western Reserve University by M. F. Utter and D. B. Keech. Since then it has been found in a wide variety of prokaryotes and eukaryotes including fungi, bacteria, plants, and animals. In mammals, PC plays a crucial role in gluconeogenesis and lipogenesis, in the biosynthesis of neurotransmitters, and in glucose-induced insulin secretion by pancreatic islets. Oxaloacetate produced by PC is an important intermediate, which is used in these biosynthetic pathways. In mammals, PC is expressed in a tissue-specific manner, with its activity found to be highest in the liver and kidney (gluconeogenic tissues), in adipose tissue and lactating mammary gland (lipogenic tissues), and in pancreatic islets. Activity is moderate in brain, heart and adrenal gland, and least in white blood cells and skin fibroblasts.