Thematic Minireview Series: A Perspective on the Biology of Phosphoenolpyruvate Carboxykinase 55 Years After Its Discovery

It is now more than 55 years since the mitochondrial form of phosphoenolpyruvate carboxykinase (GTP) (PEPCK2 ; EC 4.1.1.32) from chicken liver was first reported by Utter and Kurahashi (1). Since that time, our understanding of the properties and biological role of this enzyme has increased greatly. We now know, for example, that there are two forms of PEPCK, one in mitochondria (PEPCK-M) and another in the cytosol (PEPCK-C), and rather than being involved exclusively in gluconeogenesis, the enzyme has a broader metabolic function in the cataplerosis of citric acid cycle intermediates (removal of citric acid cycle anions), which is required for gluconeogenesis and glyceroneogenesis.