22. Regulation of skeletal muscle mass Flashcards
What is the approximate rate of protein intake/oxidation and synthesis/breakdown?
Intake/oxidation = 80g/day Synthesis/breakdown = 300g/day
What does more 13CO2 in breath mean?
More oxidation of infused tracer.
How do you measure whole body protein synthesis & breakdown?
Using stable isotope methodology, we can measure muscle protein synthesis rates by determining the incorporation of labelled AA into protein.
*if you know oxidation, you can calculate synthesis
%/day of protein synthesis in different tissues
1.15% muscle protein will be synthesised & broken down daily.
In liver, 12% will be. Therefore in 7-8 days, you will have a completely new liver.
Taking into consideration the mass, the whole body turnover % is 29% and 11% for liver.
Centrifugation steps select for……during isolation of different protein fractions from muscle.
Centrifugation steps select:
- mitochondria
- sarcoplasmic proteins (eg. signaling proteins)
- myofibrillar proteins
Describe muscle protein synthesis in different protein fractions in muscle. (mt vs. contractile)
Mitochondrial protein turnover is higher than contractile (myosin heavy chain) protein turnover.
Mito FSR > MHC FSR
Is protein synthesis & breakdown constant?
Nope, they are not constant during the day. Highly responsive to:
- food intake (protein, CHO, fat)
- exercise
- inflammatory signals
- hormones, etc.
Protein synthesis is increased during post-exercise recovery and decreased during exercise.
Effects of exercise on mixed muscle protein synthesis in trained & untrained individuals.
Mixed muscle protein synthesis is reduced during exercise, but increased for >24 hours post-exercise in untrained individuals.
Trained have a more acute response, but return to baseline much quicker than untrained ind.
What increases the myofibrillar and sarcoplasmic protein synthesis rates (FSR) following exercise?
Resistance exercise increases myofibrillar and sarcoplasmic protein synthesis.
Following exercise training, what is the acute response to exercise regarding mt & myofibrillar protein synthesis (FSR)?
Mito FSR > myo FSR
Exercise training alters the acute response to exercise.
myofibrillar: (resistance > endurance)
mitochondrial: (endurance > resistance)
This must mean that different signaling pathways are activated.
How is protein synthesis mainly regulated & how can you increase protein synthesis?
Through rate of transcription and initiation of binding of ribosome to start codon in mRNA
Also due to energy demanding amino acids and ATP/GTP.
Increased transcription levels or translation levels.
What drives the increase in MPS after exercise?
Increased translation seems to drive increased MPS after exercise.
Translation initiation
Initial binding of pre-initiation complex to mRNA
Binding of first tRNA to ribosomal subunit (methionine start amino acid)
What is the most responsive pathway to exercise & nutrition?
mTOR protein synthesis pathway
What is the effect of resistance exercise on signalling?
During exercise, AMPK activity is increased while mTOR signaling is reduced.
However, post exercise, mTOR signaling increases to promote protein synthesis.
What is S6K1 and effect of exercise on S6K1 is…
S6K1 is a downstream factor of mTOR pathway.
Effect of exercise on S6K1 is fibre-type specific.
Rapamycin and mTOR signaling
Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis.
Drug binds to mTOR & inhibits its activity
Describe the muscle wasting process with respect to aging.
With increasing age:
- increase in fat mass
- decrease in muscle mass.
Sarcopenia is a SLOW process, muscle loss is 8-10% per decade.
Wasting due to reduced anabolic response to food intake/exercise
Describe the anabolic resistance in the elderly.
Protein synthetic response to exercise is reduced in the elderly.
Protein synthesis rates after physical activity and protein intake are significantly reduced in elderly humans.
Anabolic resistance following bed-rest.
7 days of bed rest reduces anabolic response to AA intake.
*inactivity changes the activity of mTOR pathway
Describe the anabolic resistance in cancer.
The increase in protein synthesis after food intake is blunted in cancer patients.
Factors from tumour increase leg proteolysis more so than in post-op and control/non cancer state.
What are the pathways that regulate protein synthesis?
- mTOR pathway
2. translation initiation
