5'-AMP-activated protein kinase holoenzyme containing the beta-1 regulatory subunit (AMPK-beta1) (AMPK-beta1)

5'-AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme complex consisting of alpha, beta, and gamma subunits that serves as a master regulator of cellular energy homeostasis (Hardie et al., 2012; Nat Rev Mol Cell Biol). The holoenzyme containing the beta-1 regulatory subunit (PRKAB1) is of particular therapeutic interest due to its high expression in the liver and its role in mediating the effects of specific small-molecule activators (UniProt P80331). The beta-1 subunit contains a carbohydrate-binding module (CBM) that, together with the alpha-subunit kinase domain, forms the Allosteric Drug and Metabolite (ADaM) site (Hawley et al., 2012; Science). Activation of beta-1-containing AMPK complexes promotes catabolic processes such as fatty acid oxidation and glucose uptake while suppressing anabolic pathways like lipogenesis and gluconeogenesis (Cool et al., 2006; Cell Metab). Consequently, this target is being actively investigated for the treatment of metabolic disorders, including type 2 diabetes and non-alcoholic steatohepatitis (NASH). Drugs like salicylate and synthetic activators like A-769662 specifically target the beta-1 subunit to enhance AMPK activity and improve metabolic health (Myers et al., 2017; Science). This subunit-specific targeting is thought to offer a therapeutic window by focusing activity on metabolic tissues while potentially avoiding cardiac side effects associated with other isoforms.

Other names

AMPK beta-1PRKAB1-containing AMPK5'-AMP-activated protein kinase subunit beta-1AMPK beta-1 complexAMP-activated protein kinase beta-1

Direct allosteric activation via binding to the Allosteric Drug and Metabolite (ADaM) site, which is formed by the interface of the alpha-subunit kinase domain and the beta-subunit carbohydrate-binding module (Hawley et al., 2012; Science). This binding also protects the alpha-subunit Thr172 from dephosphorylation by protein phosphatases (Hunter et al., 2014; Chem Biol).