AMP-activated protein kinase catalytic subunit alpha-1 (or alpha-2) (AMPK alpha1 (PRKAA1) or AMPK alpha2 (PRKAA2))

AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme complex composed of a catalytic alpha subunit (with two isoforms: alpha-1 and alpha-2), and regulatory beta and gamma subunits. The alpha subunit contains the kinase/catalytic domain essential for AMPK’s function as a central energy sensor. This kinase is activated by increased AMP/ATP ratio (energy stress), leading to phosphorylation of Thr-172 (alpha1) or Thr-174 (alpha2), and it functions to restore energy balance by inhibiting energy-consuming biosynthetic pathways and activating ATP-generating catabolic pathways. AMPK is a well-validated drug target for metabolic diseases, including type 2 diabetes and obesity, and is also implicated in cancer, cardiovascular, and neurodegenerative diseases[1][2][3][6][7]. Drugs such as metformin and AICAR act through direct or indirect activation of the AMPK alpha catalytic domain. Biomarker assessment usually involves monitoring the level of Thr-172 phosphorylation as a readout of AMPK activity[4][6].

Other names

5'-AMP-activated protein kinase catalytic subunit alpha-15'-AMP-activated protein kinase catalytic subunit alpha-2AMPK alpha1AMPK alpha2PRKAA1PRKAA2AMP-activated protein kinase alpha subunit

Allosteric activation by AMP or ADP; Direct phosphorylation at Thr-172 by upstream kinases (LKB1, CaMKKβ); Drug-induced allosteric activation/inhibition of autoinhibition