Glossary
AMPK
AMPK is a three-part kinase switched on as the AMP:ATP ratio climbs. An overview of its subunits, the kinases above it and the metabolic targets below it.
AMPK, short for AMP-activated protein kinase, is a heterotrimer: one catalytic alpha subunit plus regulatory beta and gamma subunits. The gamma subunit senses adenine nucleotides. When ATP is consumed and the AMP:ATP and ADP:ATP ratios climb, bound AMP encourages LKB1 to phosphorylate Thr172 of the alpha subunit and shields that residue from phosphatases. A second activation path, driven by calcium via CaMKK2, works independently of cellular energy status.
Why researchers track AMPK
Activated AMPK phosphorylates substrates that switch off energy-hungry biosynthesis and switch on energy-producing breakdown: ACC1 and ACC2 (governing fatty-acid synthesis and oxidation), HMG-CoA reductase, TBC1D1, plus ULK1 and TSC2, the last two connecting it to autophagy and to the suppression of mTORC1. For that reason it is the standard readout against which most metabolic research compounds are screened, and in the usual nutrient-sensing schematic it stands across from mTOR, next to sirtuins and NAD+.
Getting the mechanism right is important: AICAR switches AMPK on directly through its metabolite ZMP, while metformin — a prescription-only reference compound — is mostly described as working indirectly, by inhibiting complex I and thereby shifting nucleotide ratios. Neither mechanism should be interpreted as a claim about outcomes.
Related terms and material
PPAR-delta · mitochondrial-derived peptide · in vitro. Reference material: MOTS-c, mitochondrial peptides. Further reading: what is AICAR.