Energy Metabolism of Muscle Flashcards
What is dystrophin?
What happens if it is deficient?
It is a protein that connects the cytoskeleton of the muscle cell to the plasma membrane of the muscle, this is important to smoothly transfer the contractile forces to the membrane
If deficient, the membrane will rupture and the muscles will be lysed and die
In the muscle, why can’t ATP be stored directly?
What molecules are converted to store the high energy phosphate bonds?
What enzyme is used to catalyze the reaction?
How can this enzyme be used for diagnostic purposes?
ATP is an allosteric regulator for many different enzymes. Storing ATP directly might interfere with their activity
Creatine is phosphorylated to creatine phosphate
Creatine (phospho) kinase is used (CK or CPK)
CPK or CK can denote muscle damage
How can the degradation of creatine phosphate be used in diagnostic purposes?
Creatine phosphate is constantly being degraded to creatinine. It will be secreted in the urine as long as you maintain your muscle mass. If it is elevated in the blood, it denotes the impairment of kidney functions
Myosin generates ADP in muscle contraction, talk about this process, what is it converted to? What enzyme is used?
2 ADP is converted to ATP and AMP through adenylate kinase
How is PFK-2 regulated in the skeletal muscle?
Cardiac muscle?
In skeletal muscle, PFK-2 cannot be phosphorylated, so it CANNOT be inhibited
1
In cardiac muscle, insulin, epinephrine, and AMP can induce PFK-2
How does AMP regulate fatty acid metabolism in the skeletal muscle?
When AMP is high, AMP-PK is activated. This can either inhibit ACC, which converts acetyl CoA to malonyl CoA. AMP-PK can also activates MCoADC, which converts malonyl CoA into acetyl CoA
Describe cardiac muscle conditions during fasting. Where will most of the energy come from?
Insulin level will be low, GLUT-4 will be low, energy will mainly come from beta-oxidation (long chain FA). High acetyl CoA will inhibit glucose going into glycolysis
Describe cardiac muscle condition when well fed
Can increase glycolysis for producing energy. Insulin inhibits beta-oxidation, it facilitates glucose uptake, it will activate PFK-2 through phosphorylation, which will activate PFK-1 by allosteric regulation
What causes ischemia in cardiac muscle?
Low O2 will inhibit mitochondrial ATP synthesis and beta-oxidation of FA. High AMP/ATP ratio will activate glycolysis (high AMP will up regulate glucose uptake as well as PFK 1 and 2)
Because ETC does not work, TCA cycle stops, pyruvate will be converted to lactate, glucose use assured by AMP levels, so it will activate AMP dependent kinase (AMP-PK), which will put GLUT-4 on the surface and take up glucose. This will activate PFK-2. This will cause an accumulation of pyruvate, resulting in lactic acidosis
Describe the resting skeletal muscle condition. Where does most of the energy come from? What if there’s enough energy?
Most of the energy come from oxidative phosphorylation, most of the energy provided by fatty acid oxidation. Increase in blood glucose will convert glucose to glycogen
The oxidation of branched chain amino acids can be used for energy production if amino acid levels are high
If there’s enough energy, the citrate level will reduce the rate of glycolysis and beta-oxidation
Describe fuel metabolism in skeletal muscles during starvation
Glucose uptake is down regulated. Fatty acids will be preferred during this time
Low ATP/high AMP will activate AMP-PK, this will deactivate ACC-2, this will lead to low malonyl CoA levels, which will activate CPT-1 and beta-oxidation, this will lead to large amounts of acetyl-CoA and inhibit pyruvate dehydrogenase
Describe fuel metabolism during the onset of exercise
The need for ATP is increased, ATP from resting state will be exhausted, the creatine phosphate stores will be depleted. Oxygen phosphorylation is not possible for at least 1 minute due to limited O2 delivery (epinephrine limitation), anaerobic glycolysis is the only quick way for ATP supply, it will activate glycogenolysis and glycolysis
Describe fuel metabolism during high intensity exercise. What is the most prominent source of energy?
Beta-oxidation and the TCA cycle will provide most of the energy. However, this is not enough, AMP levels will rise and activate glycogen phosphorylase and PFK-1.
TCA will run at its highest capacity from the accumulation of acetyl-CoA from beta-oxidation. This will make the PDC inactive, accumulating pyruvate and converting it to lactate (lactic acidosis), causing muscle damage
What uses lactate produced from high intensity exercise? How?
Lactate produced during high intensity exercise can be used by resting skeletal and cardiac muscles for energy. They convert lactate to pyruvate using lactate dehydrogenase (due to low NADH/NAD ratio)
Liver can use lactate through gluconeogenesis (cori cycle)
What occurs during long term exercise?
Aerobic oxidation of FA as well as glucose is the main energy source. Lactate diminishes. Glucose will be provided by the liver for 40 minutes. After 4 hours of exercise, gluconeogenesis increases, glycogenolysis decreases, muscle increases its use of FA
