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

5'-AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine protein kinase that serves as a central energy sensor in eukaryotic cells. The alpha subunit (AMPK-α) is the catalytic component of the heterotrimeric complex, which also includes regulatory beta and gamma subunits (UniProt). AMPK is activated in response to cellular stresses that deplete ATP, such as exercise, hypoxia, or nutrient deprivation, leading to an increase in the AMP:ATP ratio (PubMed: 22349066). Once activated via phosphorylation at Thr172, AMPK restores energy balance by stimulating catabolic pathways like fatty acid oxidation and glucose uptake while inhibiting energy-consuming anabolic processes like lipid synthesis (StatPearls). Due to its pivotal role in metabolism, AMPK-α is a primary therapeutic target for type 2 diabetes, obesity, and metabolic syndrome (Nature Reviews Drug Discovery). Additionally, its influence on cell growth and autophagy has made it a subject of interest in oncology and neurodegenerative disease research (PubMed: 27151511). Drugs targeting AMPK-α include indirect activators like metformin and direct allosteric activators currently in clinical development (Science).

Other names

PRKAA1PRKAA2AMPK alpha5'-AMP-activated protein kinase catalytic subunit alpha-15'-AMP-activated protein kinase catalytic subunit alpha-2AMP-activated protein kinase, alpha catalytic subunit

Direct allosteric activation of the AMPK complex by binding to the ADaM (allosteric drug and metabolite) site or indirect activation via inhibition of mitochondrial Complex I, leading to increased AMP levels and subsequent phosphorylation of the alpha subunit at Thr172 (PubMed: 22349066, 28103444).