Adenosine monophosphate-activated protein kinase (AMPK) (AMPK)

Adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric enzyme complex that serves as a master regulator of cellular energy homeostasis (Hardie et al., 2012, Nature Reviews Molecular Cell Biology). It is traditionally activated by increases in the AMP:ATP ratio, but it also functions as a redox sensor through specific oxidation-sensitive cysteine residues, notably Cys130 and Cys174 in the alpha subunit (Zmijewski et al., 2010, Journal of Biological Chemistry). Oxidation of these residues by reactive oxygen species (ROS) can trigger AMPK activation independently of nucleotide levels, facilitating a cellular response to oxidative stress (Shao et al., 2014, Free Radical Biology and Medicine). Once activated, AMPK promotes catabolic pathways like glucose uptake and fatty acid oxidation while inhibiting anabolic processes such as lipid synthesis (UniProt, 2024, P54646). This makes the redox-sensitive sites of AMPK a significant area of interest for treating metabolic diseases, cardiovascular conditions, and cancer, where oxidative balance is often disrupted (Kulkarni et al., 2020, Cell Metabolism).

Other names

5'-AMP-activated protein kinasePRKAProtein kinase AMP-activatedHMG-CoA reductase kinaseMetabolic master switch

AMPK is activated by an increase in the AMP:ATP ratio or through the oxidation of specific cysteine residues (Cys130/Cys174) in the alpha subunit. Activation leads to the phosphorylation of downstream targets like Acetyl-CoA Carboxylase (ACC) and TSC2, which shifts the cell from an ATP-consuming anabolic state to an ATP-generating catabolic state.