Lecture 5: Control of muscle mass Flashcards
what is muscle protein balance? 3 scenarios
- if you train and eat protein, what happens?
- 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
- what are the 2 important pathways ish for muscle protein synthesis
- explain their 4 steps
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
what are the 3 protein breakdown processes?
- 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)
explain the 5 steps of autophagy
- 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
explain the 8 steps of protein-ubiquitination pathway
- 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
what is the role of muscle protein breakdown? (2)
- essential for muscle protein turnover
- increase MPB = muscle atrophy (decrease muscle volume/mass from not using muscle or depriving yourself from energy/food)
muscle hypertrophy vs hyperplasia?
- in all humans?
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)
what are the 4 key molecular pathways that regulate muscle mass?
- do they activate or inhibit muscle synthesis?
- 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
- what is mTOR? –> goal?
- factors (3) activating mTOR –> leads to 2 flèches
- 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
- what is IGF-1?
- primarily produced where?
- produced in response to what?
- plays a role in what?
- stimulates (2)
- pathway?
- 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
where are satellite cells in the muscle?
- play a crucial role in what?
- between basal lamina and basement membrane
- plays crucial role to repair muscle cell
- 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!
- 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
- what is myostatin?
- what does it do (2)
- can be suppressed via what?
- pathway?
- amount of myostatin is from (2)
- 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
what happens if your myostatin levels are very low?
very big hypertrophy BUT can influence tendon and ligament strength
- what is a satellite cell?
- goal?
- typically in what stage? until what?
- 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))
explain steps from quiescent satellite cell to myofiber
- how long is the process?
- ACTIVATION: quiescence satellite –> activated satellite cells (self-renewal
- PROLIFERATION: activated satellite cells –> myogenic progenitor (myoblasts/baby muscle fiber)
- DIFFERENTIATION: myoblasts –> myocytes
- FUSION: myocytes –> myotubes (multiple nuclei per cell)
- MATURATION: myotubes –> myofiber
- steps 3, 4 and 5 –> 3-6 days
what is necessary for muscle growth regardless of training in the gym?
- how much?
protein consumption!
- 0.8g/kg/day for sedentary individuals (WHO rec)
- 1.6-2.2g/kg/d for resistance trained individuals
*no added benefit of eating above 1.6g/kg/d according to literature
- 1.83g/kg/d for endurance athletes (still high bc lots of breakdown during run)
how often and what type of protein should be eaten?
- across 12h feeding window during post-resistance exercise recovery period –> 4 x 20g (every 3h) had the optimal muscle growth!
- protein sources high in leucine concentrations (casein < soy < whey)
what does resistance training do to MPS vs MPB?
- how to offset?
- both increase but MPB increase is higher!
- to offset: eat protein –> then MPS increases past MPB!
*long term goal: keep muscle constantly stimulated
why is intermediate protein feeding strategy optimal for muscle protein synthesis? (2)
- at the end of the day, what matters the most?
- offsets breakdown periods –> if not breakdown periods would be too low
- need a minimum amount fo stimulate protein synthesis (thats why we dont recommend 8 x 10g every 1.5h)
- amount of protein you eat in a day!
what is the most robust stimulus to increase rate of MPS?
resistance training!
- each time you train and eat, you will have a spike in MPS
- however, the spike will be lower and lower bc your body adapts (but your baseline MPS will increase!)
what are 5 key resistance training principles?
- progressive overload
- close to failure
- stretch (not static)
- specificity
- recovery
key resistance training principles:
explain:
- progressive overload
- CLOSE TO FAILURE
PROGRESSIVE OVERLOAD:
- gradual increase in resistance
- must increase load (intensity), otherwise muscle will adapt, and load is no longer a sufficient stimulus
- or increase volume (# of reps)
CLOSE TO FAILURE:
- training the muscle to exhaustion or up to the point of exhaustion (2 reps in reserve)
- across all studies, seems to be key principle for muscle growth
key resistance training principles:
explain:
STRETCH
SPECIFICITY
RECOVERY
STRETCH
- increase in muscle size due to mechanical stretching of muscle fibers (ie very low depth in Bpress)
- mechanotransduction: muscle contains mechanosensors that activate hypertrophic process
SPECIFICITY:
- target specific muscle for desired adaptations
- muscle growth/strength is a localized response (training biceps will not make your legs stronger) BUT around 20% carryover effect for strength (ie if you only train L side, 20% increase on R side)
RECOVERY:
- rest adequately, essential for repair and growth
- dependent on experience, type of training, nutrition
why are muscles not growing if i have been participating in endurance exercise for years?
- type of muscle fibers
- training stimulus
- protein balance
- volume vs intensity
- E utilization
- TYPE of MUSCLE FIBERS targeted –> type 1 (slow twitch)
- TRAINING STIMULUS: low intensity, high volume activity –> adaptations such as mitochondrial density, increase capillarization, increased oxygen utilization –> not enough tension
- PROTEIN BALANCE: catabolic environment –> MPB occurs to meet E demands
- VOLUME VS INTENSITY: intensity of mechanical load applied to muscle during endurance exerc. is significantly lower –> hypertrophy requires muscles to be loaded close to maximum capacity to generate necessary mechanical tension and microdamage
- ENERGY UTILIZATION: body prioritizes oxidative E systems utilizing CHO and fats for long duration E –> energy efficiency focus vs muscle size increase
how do resistance exercise vs endurance exercise affect molecular pathways regulating muscle mass?
- ___________ effect –> explain!
- resistance exercise activates mTOR
- endurance exercise activates AMPK activity (inhibits mTOR)
INTERFERENCE effect: - phenomenon by which adaptation to concurrent strength training and endurance training is diminished compared to separately training only strength or endurance
- reduced response from one of the other
what is the difference in adaptations for untrained vs trained when they do only endurance vs only resistance vs concurrent training?
UNTRAINED
- Endurance only = increase endurance + lil bit hypertrophy strength
- resistance training only = increase hypertrophy strength + lil bit endurance
- concurrent: adaptations in both endurance and strength, equally
VS TRAINED:
- ET only: only endurance adaptations
- RT only: only strength adaptations
- CT: more endurance then strength adaptations!
*strength will mostly be compromised
how to circumvent compromisation of hypertrophy strength during concurrent training? (2)
- not doing endurance and strength on same day
- do strength first for neuromuscular adaptations
what is capillarization?
- key adaptation to which type of training?
- benefits? (3 ish)
- increase in number and density of capillaries around muscle fibers
- key adaptation to endurance training
- increase capillary density = increase delivery of O2 and nutrients to muscles fibers + increase removal of metabolic waste products
- increase blood flow
how to have better effects from strength training?
if you do endurance training a few weeks before!
