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.
  - Happens in presence of fructose (see “Fructose and Glucose“).
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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Summaries