Phosphoenolpyruvate carboxykinase 1 (PCK1)

Phosphoenolpyruvate carboxykinase 1 (PCK1), also known as cytosolic PEPCK, is an enzyme that catalyzes a committed and rate-limiting step in gluconeogenesis: the decarboxylation and phosphorylation of oxaloacetate to phosphoenolpyruvate using GTP, releasing carbon dioxide and GDP[1][2][5]. This reaction is critical for glucose production in the liver and kidneys, playing a pivotal regulatory role in blood glucose homeostasis. PCK1 activity is tightly controlled at the transcriptional level by hormones such as insulin (downregulates), glucagon, and glucocorticoids (upregulate), and through dietary cues[1][4]. Beyond gluconeogenesis, PCK1 is involved in glyceroneogenesis, linking carbohydrate and lipid metabolism, as well as facilitating the metabolic flexibility needed in tissues like liver, kidney, small intestine, and skeletal muscle[6]. Altered PCK1 expression or activity is implicated in the pathophysiology of diabetes, metabolic syndrome, and some cancers, making it a therapeutic and diagnostic target of interest[3][2].

Other names

PEPCKPEPCK-C (cytosolic)PCK1 (gene symbol)Phosphoenolpyruvate carboxykinase (soluble)GTP-dependent PEPCK

Enzyme inhibition (theoretical for antidiabetic agents: reduction of hepatic gluconeogenesis by PCK1 inhibition) Transcriptional regulation (by hormones influencing gene expression: glucocorticoids upregulate, insulin downregulates) Indirect modulation by metabolic pathway drugs (e.g., metformin’s action reduces gluconeogenesis, partly by decreasing PEPCK levels)