5'-AMP-activated protein kinase alpha-1 beta-1 gamma-1 heterotrimer (AMPK α1β1γ1) (AMPK α1β1γ1)

The 5'-AMP-activated protein kinase (AMPK) α1β1γ1 heterotrimer is a critical cellular energy sensor that maintains metabolic homeostasis by monitoring the ratio of AMP/ADP to ATP [Hardie et al., 2012, PubMed: 22447941]. This specific heterotrimeric complex consists of the catalytic α1 subunit (PRKAA1), the regulatory β1 subunit (PRKAB1), and the AMP-binding γ1 subunit (PRKAG1) [UniProt: P54646, Q9Y478, P54619]. Upon activation by energy stress or pharmacological agents, AMPK promotes catabolic pathways such as glucose uptake and fatty acid oxidation while inhibiting energy-consuming anabolic processes like lipid and protein synthesis [Zhang et al., 2017, PubMed: 28416520]. It plays a central role in the pathophysiology of metabolic disorders, including type 2 diabetes and obesity, making it a major target for insulin-sensitizing and lipid-lowering therapies [Day et al., 2017, PubMed: 28751405]. Pharmacological activation can occur indirectly through mitochondrial inhibition or directly via binding to the Allosteric Drug and Metabolite (ADaM) site located between the α and β subunits [Cokorinos et al., 2017, PubMed: 28319112].

Other names

AMPK alpha-1 beta-1 gamma-1PRKAA1-PRKAB1-PRKAG1 complexAdenosine monophosphate-activated protein kinase alpha-1 beta-1 gamma-1PRKAA1/PRKAB1/PRKAG1

Direct activation via binding to the Allosteric Drug and Metabolite (ADaM) site at the alpha-beta subunit interface, or indirect activation via increasing cellular AMP/ADP ratios which leads to phosphorylation of Thr172 in the activation loop of the alpha subunit by upstream kinases like LKB1 [Hardie et al., 2012, PubMed: 22447941; Cokorinos et al., 2017, PubMed: 28319112].