5'-AMP-activated protein kinase catalytic subunit alpha (AMPKα) (AMPKα)

5'-AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme complex that serves as a central energy sensor and master regulator of metabolism in eukaryotic cells. The alpha subunit (AMPKα) contains the catalytic domain responsible for the kinase activity, which is triggered by cellular energy stress indicated by a high AMP:ATP ratio (UniProt: P54646, Q13131). When activated, AMPKα restores energy balance by promoting catabolic processes such as glucose uptake and glycolysis while simultaneously suppressing anabolic pathways like gluconeogenesis and lipid synthesis (StatPearls: AMPK). In the liver, AMPK inhibits gluconeogenic gene expression (e.g., PEPCK and G6Pase) by phosphorylating transcriptional co-activators like CRTC2 (PMID: 29129784). In skeletal muscle, it stimulates glycolysis by activating PFKFB3 and facilitating the translocation of GLUT4 to the plasma membrane (PMID: 22349066). Due to its ability to lower blood glucose and improve insulin sensitivity, AMPKα is a major therapeutic target for metabolic disorders, most notably through the indirect action of metformin, the first-line treatment for type 2 diabetes (NCBI Gene: 5562).

Other names

PRKAA1PRKAA2AMP-activated protein kinase alphaAMPK alpha 1AMPK alpha 2Protein kinase AMP-activated catalytic subunit alpha

AMPKα is the catalytic subunit of the AMPK complex that is activated by an increased AMP:ATP ratio or upstream kinases like LKB1. Once activated, it phosphorylates downstream targets to stimulate ATP-producing catabolic pathways (e.g., increasing glycolysis via PFKFB3 activation and GLUT4 translocation) and inhibit ATP-consuming anabolic pathways (e.g., suppressing gluconeogenesis by inhibiting CRTC2 and FoxO1 transcription factors).