Metabolic drivers of skeletal muscle hypertrophy

Question 1

What is a + net protein balance

Answer 1

When muscle protein synthesis is greater than muscle protein breakdown

Question 2

What is translation in simple terms?

Answer 2

Protein synthesis - process by which mRNA sequence is converted to new protein sequence

Question 3

What are the 3 key steps in translation?

Answer 3

Initiation - ribosome binds to mRNA sequence
Elongation - AA added to protein chain
Termination - Removal of ribosomes + new protein form mRNA sequence

Question 4

What does mTOR do?

Answer 4

Governs the size of all body cells - driver by hypermTOR

There are 2 main strains of mTOR - mTORC1 is rapamycin sensitive and integral to controlling cell size

Question 5

What does rapamycin do?

Answer 5

Stops growth by inhibiting mTOR

Question 6

What is rheb and what process is it involved in?

Answer 6

RHEB = small GTP-binding protein, plays a critical role in MTORC1 activation.
- Rheb activates mTORC1 when it is in its GTP-bound form.

Energy stress signals (e.g., low ATP) activate AMPK, which activates TSC2 and/or directly inhibits mTORC1, reducing anabolic activity.

Question 7

Describe the process association Rheb with MTORC1 activation

Answer 7

TSC2 (as part of the TSC1/TSC2 complex) acts as a GTPase-activating protein (GAP) for Rheb, promoting the conversion of Rheb-GTP → Rheb-GDP, thereby inhibiting mTORC1 activation.

Growth signals (like insulin or IGF-1) activate PKB/Akt and p90RSK, which phosphorylate and inhibit TSC2, leading to increased Rheb-GTP and activation of mTORC1.

Energy stress signals (e.g., low ATP) activate AMPK, which activates TSC2 and/or directly inhibits mTORC1, reducing anabolic activity.