4 - Muscle Metabolism and the Exercise State Flashcards
How is muscular hexokinase regulated?
Inhibition by glucose 6-P.
How does the rate of glucose concentration change in the muscle during the fed state?
Greatly, as insulin and muscle contraction stimulate the GLUT4 transported to take up the extra glucose.
How does the rate of glycolysis change in the muscle during the fed state?
Only marginally, most of the glucose taken up is used in glycogenolysis.
How do resting myocytes in the fed state ensure they perform only enough glycolysis to support themselves?
Glucose 6-P product inhibition of hexokinase.
What is the key point of muscular glycolysis regulation?
The PFK-1/FBPase-1 complex.
How is muscular PFK-1 regulated?
+ Fructose 2,6-BisP
+ AMP
- ATP
- Citrate (CAC saturation)
Explain the effects of ATP/AMP and citrate on muscular PFK-1.
ATP lowers the affinity for the potent activator F26BP. AMP competes with ATP for this event without causing the same effect.
Citrate amplifies the effect of ATP.
Describe the regulation of the final glycolytic enzyme, pyruvate kinase.
\+ AMP \+ Fructose 1,6-BisP (feedforward activation) - ATP - Citrate (CAC saturation) - Acetyl CoA (Beta oxidation)
Briefly describe the beta oxidation inhibition mechanism.
Increased glycolysis saturates the CAC. Citrate leaves via the M-A shuttle, and produces Acetyl CoA in the cytosol. Acetyl CoA is converted to Malonyl CoA by Acetyl CoA Carboxylase (stimulated by the citrate). Malonyl CoA inhibits the CPTI transporter.
Describe the rate of muscular glycogenolysis in the fasting state.
Low, the enzymes that control this are far more sensitive to exercise signalling.
Relate the mechanism of resting state muscular beta oxidation stimulation.
It is identical to that of the liver, largely being controlled by substrate abundance and lack of CPTI inhibition.
What is the Randle Cycle?
The mutual inhibition and competition for oxidation between glucose and fatty acids in muscle and adipose tissue.
What two inhibition events are key in the Randle Cycle?
Acetyl CoA inhibition of Pyruvate Kinase
Malonyl CoA inhibition of CPTI
When muscular glycolysis in inhibited in the fasting state, what occurs to the small amounts of pyruvate that is produced?
Its gluconeogenic potential is preserved as Acetyl CoA in the mitochondrial matrix from beta oxidation inhibits pyruvate dehydrogenase (product inhibition).
What is aerobic exercise?
Low-moderate intensity exercise that can be sustained for long periods of time.
What is anaerobic exercise?
High intensity exercise such as sprinting or weightlifting.
What type of exercise are Type I muscle fibres suited to?
Aerobic exercise.
What five adaptations do Type I muscle fibres possess that makes them fit for purpose?
Moderate glycolytic ability. High oxidative capacity/Mitochondria rich. Good blood supply. More TAG stored compared to glycogen. Slower myosin ATPases.
What type of exercise are Type II muscle fibres suited to?
Anaerobic exercise.
What are Type II muscle fibres also known as?
Fast-twitch fibres or White Skeletal muscle fibres.
How are Type II muscle fibres adapted for their role?
High glycolytic capacity. More glycogen storage, less TAG. Low oxidative capacity/few mitochondria. Poor blood supply. Fast myosin ATPases.
Describe the action of Adenylate Kinase.
2x ADP -> 1x ATP + 1x AMP
Why is Adenylate Kinase used?
Because ADP cannot be used by myosin ATPases for muscle contraction, so conversion to ATP + AMP preserves energetic potential.
What are the effects of Adenylate Kinase action on the relative concentrations of ATP, ADP and AMP?
ATP decreases only by 10%.
ADP is constant and v. small.
AMP increases by the same amount ATP decreases, but due to lower initial concentration this is a 600% increase.