The enzyme 5′ AMP-activated protein kinase or AMPK or 5′ adenosine monophosphate-activated protein kinase plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low.
In eukaryotic cells, AMPK serves as a key cellular energy sensor and a master regulator of metabolism to maintain energy homeostasis.
AMPK is expressed in a number of tissues, including the liver, brain, and skeletal muscle.
AMPK activation stimulates hepatic fatty acid oxidation, ketogenesis, stimulation of skeletal muscle fatty acid oxidation and glucose uptake, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipogenesis, inhibition of adipocyte lipolysis, and modulation of insulin secretion by pancreatic beta-cells.
AMPK is a protein complex that is formed by α, β, and γ subunits, each of which takes on a specific role in both the stability and activity of AMPK.
There are 12 versions of AMPK with different tissue localizations, and different functions under different conditions.
AMPK is inhibited by insulin, leptin, by inducing various other phosphorylations.
AMPK may be inhibited or activated by various tissue-specific ubiquitinations.
AMPK is also regulated by several protein-protein interactions, and may either be activated or inhibited by oxidative factors.
When AMPK phosphorylates acetyl-CoA carboxylase 1 it inhibits synthesis of fatty acids, cholesterol, and triglycerides, and activates fatty acid uptake and β-oxidation.
AMPK stimulates glucose uptake in skeletal muscle.
AMPK stimulates glycolysis and inhibits glycogen synthesis
AMPK inhibits the energy-intensive protein biosynthesis process.
AMPK activation signifies low energy within the cell, so protein synthesis is inhibited.
AMPK activates autophagy by directly and indirectly activating.
AMPK stimulates mitochondrial biogenesis, by promoting gene transcription in mitochondria.
AMPK also activates anti-oxidant defenses.
During skeletal muscle activity that takes place during exercise there is increased mitochondrial biogenesis and capacity, increased muscle glycogen, an increase in enzymes which specialize in glucose uptake in cells such as GLUT4 and hexokinase II: all thought to be mediated in part by AMPK.
AMPK has a role in increasing blood supply to exercised/trained muscle cells by stimulating and stabilizing both vasculogenesis and angiogenesis.
Increases in the AMP:ATP ratio occur during single bouts of exercise and long-term training.
During acute exercise, AMPK allows the contracting muscle cells to increase expression of hexokinase II, translocation of GLUT4 to the plasma membrane, for glucose uptake, and by stimulating glycolysis, to meet energy needs.
With long-term training regimen, AMPK facilitates contracting muscle adaptations to a metabolic transition resulting in a fatty-acid oxidation approach to ATP generation as opposed to a glycolytic approach: upregulates activating oxidative enzymes.
AMPK protein abundance has been shown to increase in skeletal tissue with endurance training, its level of activity has been shown to decrease with endurance training in both trained and untrained tissue
With exercise is an increase in fatty acid metabolism, which provides more energy for the cell.
AMPK’s regulate fatty acid oxidation by the phosphorylation and inactivation of acetyl-CoA carboxylase.
AMPK also plays an important role in lipid metabolism in the liver.
AMPK is responsible in part for exercise-induced glucose uptake.
Mitochondrial enzymes, increase in expression and activity in response to exercise.
AMPK is required for increased peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) expression in skeletal muscle in response to creatine depletion.
Loss of AMPK alters the sensitivity of glucose sensing cells: pancreatic beta cells and hypothalamic neurons decreases the sensitivity of these cells to changes in extracellular glucose concentration.
AMPK activates on response to metformin.
AMPK may have a role in tumor suppression.
AMPK activator metformin was used to treat diabetes found a correlation with a reduced risk of cancer, compared to other medications.
AMPK response to exercise decreases with increased training duration.