Phosphoenolpyruvate carboxykinase 2, mitochondrial (PCK2)

Phosphoenolpyruvate carboxykinase 2, mitochondrial (PCK2), is a **mitochondrial enzyme** and an isoform of the phosphoenolpyruvate carboxykinase family. It catalyzes the GTP-dependent conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), a key, rate-limiting step in gluconeogenesis, thereby linking glycolytic and tricarboxylic acid (TCA) cycle intermediates within mitochondria[1][5]. Unlike the cytosolic isoform (PCK1), PCK2 is broadly expressed in various tissues, including non-gluconeogenic organs such as brain, pancreas, and immune cells, and is constitutively active. PCK2 has roles in metabolic adaptation, supporting cell growth and survival in nutrient-depleted or stressful environments, and is involved in cancer cell metabolism and inflammatory responses. In immune cells (e.g., Kupffer cells), upregulation or altered localization of PCK2 modulates inflammatory signaling, notably through NF-κB and MAPK/AKT phosphorylation pathways. PCK2 is under investigation as a therapeutic target in metabolic disorders, cancer, and inflammatory conditions, but direct clinical drugs are not available[1][2][3][4].

Other names

PEPCK-MPEPCK2mtPCK2Phosphoenolpyruvate carboxykinase [GTP], mitochondrialPEP carboxykinasephosphopyruvate carboxylase

Inhibition of PCK2 can decrease inflammatory cytokine production via downregulation of AKT/MAPK/NF-κB pathway activation in immune cells[2][3]. Blockade can induce tumor cell death or limit growth by restricting metabolic flexibility under stress[4]. Knockdown may suppress metabolic reprogramming associated with cancer and immune response.