Phosphoenolpyruvate carboxykinase, cytosolic (PEPCK-C)

Phosphoenolpyruvate carboxykinase, cytosolic (PEPCK-C), encoded by the PCK1 gene, is a critical enzyme in gluconeogenesis that catalyzes the conversion of oxaloacetate to phosphoenolpyruvate while releasing carbon dioxide and using GTP as a phosphate donor[1][6]. This reaction is a rate-limiting and highly regulated step in the generation of glucose from non-carbohydrate sources, particularly in the liver and kidney. PEPCK-C also plays roles in glyceroneogenesis and the removal of intermediates from the citric acid cycle (cataplerosis), thereby contributing to overall energy metabolism, amino acid cycling, and lipid biosynthesis. Its dysregulation has been implicated in diabetes, metabolic syndrome, and other metabolic diseases. Research tools and small-molecule inhibitors targeting PEPCK-C are used to explore its physiological function and therapeutic potential, but clinically approved drugs against this target do not exist as of 2024[4][5][6].

Other names

PCK1PEPCK-CPhosphoenolpyruvate carboxykinase (GTP), cytosolic

Enzyme inhibitor (small molecules inhibit gluconeogenic function of PEPCK-C, reducing hepatic glucose output). Allosteric modulation and covalent inhibition have both been reported in preclinical studies.