Lecture 33: amino acid sensing & anabolic resistance Flashcards
How does the body respond to protein intake?
Protein ingestion stimulates increase in protein synthesis
What happens to protein synthesis as more protein is consumed?
As more protein is consumed protein synthesis increases until about 25grams where the increase starts to reach a plateau. Amino acids not used in protein synthesis are targeted for oxidation as a result.
When does protein synthesis happen following protein intake?
Protein synthesis following protein intake is at its maximum rate between 1 and 2 hours after consumption.
However this increase is short-lived.
What pathway is involved in protein synthesis following consumption?
Stimulation of protein synthesis after protein consumption is reduced by rapamycin which means the mTORC1 pathway is what causes it.
What are 4BP1 and S6K?
Proteins used as a measurement of mTORC1 activity and are downstream targets of mTORC1
What does leucine do to MPS?
Leucine stimulates MPS via mTORC1
What is the effect of arginine on muscle protein synthesis?
Arginine is often involved in synthesis of nitric oxide which causes increase in blood flow to muscles and in turn muscle protein synthesis via mTORC1.
How are intra and extracellular concentration of amino acids correlated?
No real correlation between plasma concentration and intracellular concentration.
How are essential amino acids and change in protein synthesis correlated?
Increase in essential amino acids and change in protein synthesis are correlated and there is an increase in protein synthesis following increase in blood amino acid concentration.
How is intracellular amino acid concetration inscreased?
SNAT2 receptor detects increase in extracellular amino acids and in turn internalizes some amino acids.
Higher intracellular amino acids can be created by lysosomes.
How does consumption of nutrients including protein increase the activation of the mTOR pathway?
Insulin stimulates Akt which stimulates PRAS40 activating mTOR.
For full activation mTOR needs to bind to a lysosome and amino acids facilitate this binding.
Rheb is activated by mTOR and as a result muscle protein synthesis is activated.
summary of point:
presence of amino acids are essential for any protein synthesis to occur.
How does leucine activate the mTOR pathway?
Leucyl-tRNA synthetase provides GTP to Rheb which is a protein that needs to be activated for the mTOR pathway to take place.
*This is the protein that combines leucine to tRNA.
How does the cell sense protein consumption?
Leucyl-tRNA detects leucine presence and in turn activates rheb and allows the pathway to take place.
What is the role of LRS in protein synthesis?
in the absence of LRS the activation of mTOR doesn’t work. LARS is needed for translocation to the lysosome and activation of mTOR.
