B: Muscle gene regulation

Question 1

Type I muscle fibres

Answer 1

• Oxidative metabolism
• Slow twitch, slow contraction
• Mitochondria rich
• Fatigue resistant
• Endurance tasks, posture maintenance

Question 2

Type IIa muscle fibres

Answer 2

• Oxidative metabolism
• Fast twitch, fast contraction
• Fatigue rapidly
• Strength + speed

Question 3

Type IIb muscle fibres

Answer 3

• Glycolytic metabolism
• Fast twitch, quick contraction
• Fatigue rapidly
• Strength + speed

Question 4

Type IId muscle fibres

Answer 4

• Glycolytic metabolism
• Fast twitch, fast contraction
• Fatigue rapidly
• Strength + speed

Question 5

Glycolytic metabolism

Answer 5

• Occurs in cytoplasm
  
  • Occurs rapidly
  • Can support 2 min of tetanic contraction
  • Generates 2 ATP per glucose contraction
  • Generates lactic acid

Question 6

Oxidative metabolism

Answer 6

• Occurs in mitochondria
  
  • Generates 36 ATPs per glucose molecule
  • Relatively slow
  • Can support 40 min to several hours of tetanic contraction

Question 7

Fast-glycolytic fibres in skeletal muscle

Answer 7

• Adapted for generating maximum forces for short periods of time
• Less blood, mitochondria + myoglobin
• Low fat, high glycogen
• Rely on glycogen + anaerobic glycolysis
• Short duration, high intensity contractions
• Anaerobic exercise stimulates enlargement of muscle fibres through production of new microfilaments.

Question 8

Slow oxidative fibres

Answer 8

• Adapted for extended aerobic work
• Lots of blood, high mitochondria, myoglobin
• Able to sustain low intensity contraction for long periods
• Through aerobic conditioning, muscle fibres can acquire greater oxidative capacity.

Question 9

Explain how MEF2 transcription factor is changed from inactive to active form —

Answer 9

MEF2 is a muscle transcription factor that turns on several muscle specific genes.
. MEF2 is controlled by HDAC4 and HDAC5
. These bind to MEF2 in the nucleus and repress it
. HDAC kinase is activated in response to calcium and phosphorylates HDAC4 and HDAC5 –> this makes them translocate out of the nucleus.

Question 10

Muscle activity sensing system —

Answer 10

. Sustain low amplitude contraction: net effect is elevated calcium.
. Calcium binds to calmodulin + activates it
. Activated calmodulin activates calcineurin
. Activated calcineurin dephosphorylates NFAT in cytosol.
. Dephosphorylated NFAT translocates into the nucleus.
. In the nucleus it binds to promoters of muscle specific genes and turns them on.

Question 11

What is ubiquitin + ubiquitin ligase? -

Answer 11

When it is attached to a protein, the protein is targeted for degradation by proteasome.
Ubiquitin ligases are enzymes that attach ubiquitin to specific proteins.

Question 12

What is the relationship between myogenin and muscle atrophy? —

Answer 12

Denervation –> muscle atrophy.
Myogenin is upregulated following denervation
Myogenin regulates expression of E3 ubiquitin ligases MuRF1 and atrogin-1 which cause ubiquitin to be attached to several key muscle proteins + causes muscle atrophy.

Question 13

Difference between NFAT, myogenin & MEF2

Answer 13

Myogenin: Denervation –> muscle atrophy.
Myogenin is upregulated following denervation .Myogenin regulates expression of E3 ubiquitin ligases MuRF1 and atrogin-1 which cause ubiquitin to be attached to several key muscle proteins + causes muscle atrophy.
NFAT: Sustain low amplitude contraction: net effect is elevated calcium.
Calcium binds to calmodulin + activates it
Activated calmodulin activates calcineurin
Activated calcineurin dephosphorylates NFAT in cytosol. Dephosphorylated NFAT translocates into the nucleus.In the nucleus it binds to promoters of muscle specific genes and turns them on.
MEF2: controlled by HDAC4 and HDAC5
These bind to MEF2 in the nucleus and repress it. HDAC kinase is activated in response to calcium and phosphorylates HDAC4 and HDAC5 –> this makes them translocate out of the nucleus.