M9 Nutrition, energy and AA sensing

Question 1

What is responsible for the regulation of protein synthesis

Answer 1

• AA responsible to regulation of protein syn
• ~25g protein req for maximal stimulation of protein synthesis

Question 2

Effects of continuously infusing protein

Answer 2

• Effect duration is short
• Rapidly ↑intially
• ↓after ~2hrs

Question 3

mTORC1 vs mTORC 2

Answer 3

• mTORC1 is sensitive to rapamycin
  
  • ∴rapamycin inhibits mTORC1 but not mTORC2

Question 4

2 main downstream pathways of mTORC1

Answer 4

• 4EBP1 and S6K are downstream targets of mTORC1

Question 5

Different AA’s effect on MPS

Answer 5

• Leucine stimulates MPS via mTORC1
• Arginine → stimualtes S6K phosphorylation, also stimulates mTOR → ∴stimulates protein synthesis
  
  • Independent of NO pathway (i.e. not stimulating mTOR via dilating vessels → allowing ↑[AA]

Question 6

Extracellular vs intracellular AA availability on MPS

Answer 6

• MPS is modulated by extracellular, not intracellular AA availability

Question 7

LAT1

Answer 7

• transports leucine
• Directly signals mTOR
• Or ↑intracellular AA availability
• May be translocated to lysosomes → crucial in activation of mTOR

Question 8

Intracellular signalling required to activate mTORC1

Answer 8

• mTORC1 needs to be translocated to a lysosome for activation

Question 9

What is the effect of AA ingestion and resistance exercise?

Answer 9

• AA ingestion and resistance exercise → changes the levels of AA transporters

Question 10

Activation of mTOR

Answer 10

• Insulin stimulate Akt → PRAS40 → phosphorylates mTOR and localises mTOR to lysosomes to be activated by the RAGS system
  
  • AA are crucial to maximally stimulate mTOR
    
    • AA can bind only if GDP loading is changed (achieved by LRS)

Question 11

Leucyl-tRNA synthetase

Answer 11

1. Couples leucine to tRNA → producing leucyl-tRNA → Used by ribosomes to build new protein
2. Have GTPase activity → activated by leucine → bind, change and activated mTOR
   
   • A intracellular leucine sensor
   • LRS is required for translocation to the lysosome and further activation of mTOR

Question 12

Proteins modulating the activity of mTOR

Answer 12

• SCL38A9 → senses lysosomal arginine → signals mTOR

Question 13

Non-essential AA regulating protein turnover

Answer 13

• Looks at serine biosynthesis → related to glycine and the folate cycle
  
  • Glutamine req for serine synthesis
  • Knocking out this pathway → trouble activating 4EBP1

Question 14

Attenuated anabolic resistance to EAA in elderly

Answer 14

• ↓myofibrillar and mitochondrial protein synthesis
• No response to ↑leucine ingestion (↑availability of EAA → does not restore MPS rates)

Question 15

What may inflammation induce?

Answer 15

• may induce anabolic resistance
• Control inflam (treated with glycine) → improve anabolic response to leucine
• Mechanism is unclear

Question 16

Macronutrients on anabolic response to protein (i.e. carbs)

Answer 16

• Carb ingestion → insignificant to anabolic response

Question 17

However, what are the effects of combining glucose and fructose intake?

Answer 17

• ↑carbohydrate oxidation → ↓use of muscle glycogen → ↑glycogen storage → ↑performance

Question 18

Effects of chronic sucrose ingestion?

Answer 18

• Chronic sucrose intake → get fat → accelerates sarcopenia through alterations in insulin sensitivity and ↓MPS