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9. Muscles and Muscle Metabolism. Introduction: Muscle Metabolism – Energy for Contraction. Energy is never created nor destroyed, only stored or released Bonds = energy – ATP is the currency for cellular energy Energy is stored in the bonds. Muscle Metabolism: Energy for Contraction.

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Muscles and Muscle Metabolism

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    1. 9 Muscles and Muscle Metabolism

    2. Introduction: Muscle Metabolism – Energy for Contraction • Energy is never created nor destroyed, only stored or released • Bonds = energy – ATP is the currency for cellular energy • Energy is stored in the bonds. MDufilho

    3. Muscle Metabolism: Energy for Contraction • ATP only source used directly for contractile activities • Move and detach cross bridges, calcium pumps in SR, return of Na+ & K+ after excitation-contraction coupling • Available stores of ATP depleted in 4–6 seconds MDufilho

    4. Muscle Metabolism: Energy for Contraction • ATP regenerated by: • Direct phosphorylation of ADP by creatine phosphate (CP) • Anaerobic pathway (glycolysis  lactic acid) • Aerobic respiration MDufilho

    5. Figure 9.19a Pathways for regenerating ATP during muscle activity. Direct phosphorylation Coupled reaction of creatine Phosphate (CP) and ADP Energy source:CP Creatine kinase Creatine Oxygen use:None Products: 1 ATP per CP, creatine Duration of energy provided: 15 seconds MDufilho

    6. Figure 9.19b Pathways for regenerating ATP during muscle activity. Anaerobic pathway Glycolysis and lactic acid formation Energy source:glucose Glucose (from glycogen breakdown or delivered from blood) Glycolysis in cytosol 2 Pyruvic acid net gain Released to blood Lactic acid Oxygen use:None Products:2 ATP per glucose, lactic acid Duration of energy provided:30-40 seconds,or slightly more MDufilho

    7. Anaerobic Pathway • At 70% of maximum contractile activity • Bulging muscles compress blood vessels; oxygen delivery impaired • Pyruvic acid converted to lactic acid • Lactic acid • Diffuses into bloodstream • Used as fuel by liver, kidneys, and heart • Converted back into pyruvic acid or glucose by liver MDufilho

    8. Anaerobic Glycolysis • Fast pathway, but does not produce much ATP • Important for the first 30 – 40 sec. of strenuous activity if enzymes and fuel are available • Stored ATP, CP and glycolysis can support strenuous muscle activity for 60 sec. • At full speed lactic acid accumulates, lowering pH which halts reaction • At full speed, glucose might not be supplied fast enough MDufilho

    9. Aerobic Pathway • Produces 95% of ATP during rest and light to moderate exercise; slow • Series of chemical reactions that require oxygen; occur in mitochondria • Breaks glucose into CO2, H2O, and large amount ATP • Fuels - stored glycogen, then bloodborne glucose, pyruvic acid from glycolysis, and free fatty acids MDufilho

    10. Figure 9.19c Pathways for regenerating ATP during muscle activity. Aerobic pathway Aerobic cellular respiration Energy source: glucose; pyruvic acid; free fatty acids from adipose tissue; amino acids from protein catabolism Glucose (from glycogen breakdown or delivered from blood) Pyruvic acid Fatty acids Aerobic respiration in mitochondria Aerobic respiration in mitochondria Amino acids 32 net gain per glucose Oxygen use: Required Products: 32 ATP per glucose, CO2, H2O Duration of energy provided: Hours MDufilho

    11. Aerobic Respiration – Krebs Cycle • Occurs in the mitochondrial matrix and is fueled by pyruvic acid (from glucose) and fatty acids • Prep. Step - Pyruvic acid is converted to acetyl CoA • Requires oxygen, but does not directly use it • Preferred method of ATP production • During rest/light exercise AR yields 95% of ATP needed MDufilho

    12. Krebs Cycle • Coenzyme A shuttles acetic acid to an enzyme of the Krebs cycle • Each acetic acid is decarboxylated and oxidized, generating: • 3 NADH + H+ • 1 FADH2 • 2 CO2 • 1 ATP MDufilho

    13. Figure 24.7 Simplified version of the Krebs (citric acid) cycle. Carbon atom Electron trans- port chain and oxidative phosphorylation Glycolysis Krebs cycle Inorganic phosphate Coenzyme A Cytosol Pyruvic acid from glycolysis Transitional phase Mitochondrion (matrix) Oxaloacetic acid (pickup molecule) Citric acid (initial reactant) Isocitric acid Malic acid Krebs cycle Fumaric acid α-Ketoglutaric acid Succinic acid Succinyl-CoA MDufilho

    14. Summary of ATP Production • Complete oxidation of 1 glucose molecule • Glycolysis + Krebs cycle + electron transport chain  CO2 + H2O  32 molecules ATP • By both substrate-level and oxidative phosphorylation • But, energy required to move NADH + H+ generated in glycolysis into mitochondria  final total ~ 30 molecules ATP • Still uncertainty on final total MDufilho

    15. Figure 24.12 Energy yield during cellular respiration. Mitochondrion Cytosol Electron shuttle across mitochondrial membrane Electron transport chain and oxidative phosphorylation Glycolysis 2 Acetyl CoA Krebs cycle Pyruvic acid Glucose (4 ATP – 2 ATP used for activation energy) by substrate-level phosphorylation by substrate-level phosphorylation by oxidative phosphorylation Typical ATP yield per glucose MDufilho

    16. Energy Systems Used During Sports • Aerobic endurance • Length of time muscle contracts using aerobic pathways • Anaerobic threshold • Point at which muscle metabolism converts to anaerobic MDufilho

    17. Figure 9.20 Comparison of energy sources used during short-duration exercise and prolonged-duration exercise. Short-duration exercise Prolonged-duration exercise End of exercise 30–40 seconds 6 seconds 10 seconds Hours ATP is formed from creatine phosphate and ADP (direct phosphorylation). Glycogen stored in muscles is broken down to glucose, which is oxidized to generate ATP (anaerobic pathway). ATP stored in muscles is used first. ATP is generated by breakdown of several nutrient energy fuels by aerobic pathway. MDufilho

    18. Muscle Fatigue • Physiological inability to contract despite continued stimulation • Occurs when • Ionic imbalances (K+, Ca2+, Pi) interfere with E‑C coupling • Prolonged exercise damages SR and interferes with Ca2+ regulation and release • Total lack of ATP occurs rarely, during states of continuous contraction, and causes contractures (continuous contractions) MDufilho

    19. Excess Postexercise Oxygen Consumption • To return muscle to resting state • Oxygen reserves replenished • Lactic acid converted to pyruvic acid • Glycogen stores replaced • ATP and creatine phosphate reserves replenished • All require extra oxygen; occur post exercise MDufilho

    20. Heat Production During Muscle Activity • ~40% of energy released in muscle activity useful as work • Remaining energy (60%) given off as heat • Dangerous heat levels prevented by radiation of heat from skin and sweating • Shivering - result of muscle contractions to generate heat when cold MDufilho

    21. Skeletal Muscle Cramps Cause • Insufficient blood flow or oxygen = anaerobic ATP production • Lactic acid accumulates and causes muscle irritation • Due to dehydration and insufficient K+ , Ca 2+ and rarely Na+ Prevention • Hydration, fitness and adequate diet MDufilho

    22. Muscular Dystrophy • Duchenne muscular dystrophy (DMD): • Most common and severe type • Inherited, sex-linked, carried by females and expressed in males (1/3500) as lack of dystrophin • Cytoplasmic protein that stabilizes sarcolemma • Fragile sarcolemma tears Ca2+ entry  damaged contractile fibers  inflammatory cells  muscle mass drops • Victims become clumsy and fall frequently; usually die of respiratory failure in 20s MDufilho

    23. Muscular Dystrophy • No cure • Prednisone improves muscle strength and function • Myoblast transfer therapy disappointing • Coaxing dystrophic muscles to produce more utrophin (protein similar to dystrophin) successful in mice • Viral gene therapy and infusion of stem cells with correct dystrophin genes show promise MDufilho