AMPK

  • Master regulator of metabolism.
    • Restores energy balance during metabolic stress.
  • Activated by depletion in ATP supplies.
    • Low glucose, heat shock, and other energy stresses.
    • ATP -> donates phosphor -> ADP -> donates phosphor -> AMP.
    • Energy stresses show up as changes in AMP:ATP or ADP:ATP ratios.
  • Once AMP pool is formed: fork in the road.
    • AMP Kinase pathway (AMPK): breakdown and burn fat, energy.
    • AMP Deaminase pathway (AMPD): build and store fat, energy.
  • AMPK restores ATP levels during metabolic stress.
    • Inhibits ATP-consuming pathways, avoiding build-up of macro-molecules.
      • Protein synthesis.
      • Fatty acid synthesis.
      • Sterol synthesis.
      • Glycogen synthesis.
    • Activates ATP generating pathways, breaking down macro-molecules.
      • Breakdown of fatty acids: fatty acid oxidation.
      • Breakdown of glucose: glycolysis.
      • Glucose uptake.
      • Autophagy.
    • AMPK protein synthesis inhibition is mediated by direct inhibition of the mTORC1 complex.
      • AMPK and mTORC1 function antithetically in the regulation of cellular metabolism.
      • Ie, mTORC1 is anabolic and AMPK is catabolic.
    • AMPK pathway activation potential treatment of metabolic diseases.
      • Diabetes, obesity, inflammation, and cancer (inhibits cell growth and proliferation).
      • Metformin partly works through AMPK activation (or AMPD inhibition).

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