Lecture 5: Control of muscle mass Flashcards
1
Q
what is muscle protein balance? 3 scenarios
- if you train and eat protein, what happens?
A
- relationship between muscle protein synthesis and muscle protein breakdown
- muscle mass is gained if synthesis > breakdown
- muscle mass is lost if synthesis < breakdown
- muscle mass remains stable if 2 processes are equal
*constant fluctuation, remember graph! - if you train, both MPS and MPB increase but MPB increases more! to offset, need to eat protein –> then MPS > MPB
2
Q
- what are the 2 important pathways ish for muscle protein synthesis
- explain their 4 steps
A
TRANSCRIPTION (DNA to mRNA):
1. initiation
2. elongation
3. termination
4. mRNA processing
TRANSLATION (mRNA to protein)
1. initiation
2. elongation
3. termination
4. folding and modifications
*using ribosome, tRNA, aa
3
Q
what are the 3 protein breakdown processes?
A
- proteolysis: general breakdown of proteins
- autophagy: recycling of cellular components
- ubiquitin-proteasome system: targeted breakdown of proteins (due to mutation or damage or cell wants to break it down)
4
Q
explain the 5 steps of autophagy
A
- signal –> autophagy induction –> reaches phagophore
- LC3 (degradation proteins form a circle around what needs to be degraded –> elongation and engulfment
- autophagosome formation (closed circle with phagophore and LC3) around déchets
- autolysosome –> lysosome engults protein and spits out amino acids (?)
- lysosomal degradation
*lysosome = anabolic shuttle: brings stuff to place of syntehsis
5
Q
explain the 8 steps of protein-ubiquitination pathway
A
- ubiquitin activation –> E1 activates ubiquinone using ATP! (produces AMP + PPi)
- ubiquitin conjugation –> E2 receives ubiquitin from E1
- Ubiquitin ligation –> ligase transfers ubiquitin from E2 to protein
- polyubiquination –> chain of ubiquitin aded to the protein = will serve as recognition
- recognition of ubiquitin tail by proteasome –> protein + ubiquitin tail –> bind to 19S of proteosome
- deubiquitination and unfolding –> ubiquitin removed + protein unfolded by ATPase
- proteolysis –> degradation of protein in 20S
- peptide and ubiquitin recycling
6
Q
what is the role of muscle protein breakdown? (2)
A
- essential for muscle protein turnover
- increase MPB = muscle atrophy (decrease muscle volume/mass from not using muscle or depriving yourself from energy/food)
7
Q
muscle hypertrophy vs hyperplasia?
- in all humans?
A
HYPERTROPHY:
- increase in size (volume/cross-sectional area) of existing muscle fibers
- in humans!
HYPERPLASIA
- increase in number of muscle fibers! –> muscle fibers grow and split into smaller fibers
- does not occur in humans (expect if on drugs)
8
Q
what are the 4 key molecular pathways that regulate muscle mass?
- do they activate or inhibit muscle synthesis?
A
- mTORC1 (mechanistic target of rapamyacin complex 1) –> main driver of growth! increases muscle synthesis
- IGF-1 (insulin-like growth factor-1 = hormone) –> activates mTORC1 = activate MPS
- AMPK (activated protein kinase): inhibit mTORC1 = inhibit MPS
- myostatin: body’s natural muscle growth stopper: inhibits mTORC1 + directly inhibits MPS
9
Q
- what is mTOR? –> goal?
- factors (3) activating mTOR –> leads to 2 flèches
A
- mTOR = master growth regulator of muscle protein sythesis
- goal = promotes muscle hypertrophy when activated by key signals
1. nutrients (especially aa like leucine)
2. growth factors like IGF-1
3. mechanical stimuli (resistance exercise)
–> activate mTOR –> increase MPS –> increase muscle growth
10
Q
- what is IGF-1?
- primarily produced where?
- produced in response to what?
- plays a role in what?
- stimulates (2)
- pathway?
A
- hormone that promotes muscle hypertrophy
- liver
- muscle specific IGF-1 –> produces in response to muscle contraction
- plays a role in local muscle repair and growth
- stimulates MPS and muscle cell growth (satellite cell activation)
- IGF1 (or growth factors) –> P13K –> AKT –> mTORC1 –> increase MPS
11
Q
where are satellite cells in the muscle?
- play a crucial role in what?
A
- between basal lamina and basement membrane
- plays crucial role to repair muscle cell
12
Q
- what is AMPK? activated when?
- AMP = signal of what?
- which enzyme converts ADP to AMP?
- what happens when high glucose/energy?
- vs low glucose/energy
- pathway!
A
- AMPK = energy sensor that is activated when energy levels are low (high AMP/ATP ratio)
- AMP = signal of low E availability –> ATP is used up, becomes ADP –> when E demande is extremely high, ADP further converted to AMP via adenylate kinase
- high glucose: AMPK not activated –> mTORC1 is activated –> MPS
- low glucose: ratio of AMP/ATP increases when cell is E-deprived –> signals cells to restore E balance –> activates AMPK –> increase in glucose uptake + fat oxidation to produce more ATP + inhibit anabolic processes like MPS (consume ATP)
*AMPK activated –> inhibits mTOR + activates TSC1, TSC2 –> inhibit mTORC
13
Q
- what is myostatin?
- what does it do (2)
- can be suppressed via what?
- pathway?
- amount of myostatin is from (2)
A
- negative regulator of muscle growth
- inhibits muscle hypertrophy by limiting fiber growth and satellite cell activity + enhances protein degradation pathways
- can be suppressed via participation in resistance exercise (anabolic)
- myostatin inhibits AKT = influences transcription (to increase protein degradation) + inhibits mTOR + inhibits myogenesis
- from genetics + number of androgen receptors
14
Q
what happens if your myostatin levels are very low?
A
very big hypertrophy BUT can influence tendon and ligament strength
15
Q
- what is a satellite cell?
- goal?
- typically in what stage? until what?
A
- muscle stem cells located on muscle fiber surface
- only means of muscle fiber repair and growth after damage
- typically in a quiescent stage (inactive) until muscle membrane is damaged (damaging layers the satellite cells are in (ie basement membrane))
