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AMPK

Category: Pathways · Last updated

AMPK (5'-AMP-activated protein kinase) is a heterotrimeric serine/threonine kinase that senses cellular energy state through the ratio of AMP to ATP and orchestrates catabolic responses when energy is low.

Activation

AMPK is activated when:

  • Cellular AMP rises (energy stress, glucose deprivation, hypoxia, exercise)
  • The upstream kinase LKB1 phosphorylates the AMPK α-subunit Thr172
  • Other upstream kinases (CaMKKβ) phosphorylate the same site in calcium-driven contexts

Downstream effects

Active AMPK:

  • Stimulates glucose uptake (GLUT4 translocation in skeletal muscle, independent of insulin)
  • Stimulates fatty-acid oxidation via inhibition of acetyl-CoA carboxylase
  • Inhibits anabolic processes (mTOR, lipid synthesis, protein synthesis)
  • Promotes mitochondrial biogenesis via PGC-1α
  • Promotes autophagy via ULK1 phosphorylation

Relevance to research peptides

  • MOTS-c · the mitochondrial-derived peptide activates AMPK in skeletal muscle and is one of the few endogenous peptides characterized as a direct AMPK activator (Lee et al., Cell Metab 2015; PMID 25738459)

See also

References

  • Hardie DG. "AMPK — sensing energy while talking to other signaling pathways." Cell Metab. 2014;20(6):939-52.
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