AMPK (AMP-activated protein kinase) is a heterotrimeric enzyme built from a catalytic alpha subunit and regulatory beta and gamma subunits. Adenine nucleotides bind the gamma subunit: as ATP is spent and the AMP:ATP and ADP:ATP ratios rise, AMP binding promotes phosphorylation of Thr172 on the alpha subunit by LKB1 and protects that site from dephosphorylation. Calcium-driven activation through CaMKK2 provides a second, energy-independent route.
Why AMPK matters
Once active, AMPK phosphorylates targets that shut down ATP-consuming synthesis and open ATP-generating catabolism: ACC1 and ACC2 (fatty-acid synthesis and oxidation), HMG-CoA reductase, TBC1D1, and ULK1 and TSC2, which links it to autophagy and to mTORC1 suppression. It is therefore the readout most metabolic research compounds are screened against, and it sits opposite mTOR in the standard nutrient-sensing diagram alongside sirtuins and NAD+.
Attribution matters here: AICAR activates AMPK directly via its ZMP metabolite, whereas metformin, a prescription-only reference compound, is generally reported to act indirectly through complex I inhibition and the resulting nucleotide shift. Neither mechanism should be read as an outcome claim.
Related terms and material
PPAR-delta · mitochondrial-derived peptide · in vitro. Reference material: MOTS-c, mitochondrial peptides. Further reading: what is AICAR.