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PowerPoint® Lecture Slides prepared by Barbara Heard, Atlantic Cape Community College CHAPTER 9 Muscles and Muscle Metabolism © Annie Leibovitz/Contact Press Images © 2013 Pearson Education, Inc. 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. 5/23/2017 2 MDufilho 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 5/23/2017 MDufilho 3 Muscle Metabolism: Energy for Contraction • ATP regenerated by: – Direct phosphorylation of ADP by creatine phosphate (CP) – Anaerobic pathway (glycolysis lactic acid) – Aerobic respiration 5/23/2017 MDufilho 4 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 5/23/2017 Oxygen use: None Products: 1 ATP per CP, creatine Duration of energy provided: 15 seconds MDufilho 5 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 net gain Released to blood 5/23/2017 Pyruvic acid Lactic acid Oxygen use: None Products: 2 ATP per glucose, lactic acid Duration of energy provided: 30-40 seconds, or slightly more MDufilho 6 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 5/23/2017 MDufilho 7 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 5/23/2017 8 MDufilho 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 5/23/2017 MDufilho 9 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 Amino acids Aerobic respiration in mitochondria 32 net gain per glucose Oxygen use: Required Products: 32 ATP per glucose, CO2, H2O Duration of energy provided: Hours 5/23/2017 MDufilho 10 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 5/23/2017 11 MDufilho 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 5/23/2017 MDufilho 12 Figure 24.7 Simplified version of the Krebs (citric acid) cycle. Glycolysis transKrebs Electron cycle port chain and oxidative phosphorylation Carbon atom 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 Succinic acid 5/23/2017 MDufilho α-Ketoglutaric acid Succinyl-CoA 13 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 5/23/2017 MDufilho 14 Figure 24.12 Energy yield during cellular respiration. Mitochondrion Cytosol Electron shuttle across mitochondrial membrane Glycolysis Glucose 2 Acetyl CoA Pyruvic acid Krebs cycle Electron transport chain and oxidative phosphorylation (4 ATP – 2 ATP used for activation energy) by substrate-level phosphorylation by substrate-level phosphorylation by oxidative phosphorylation Typical ATP yield per glucose 5/23/2017 MDufilho 15 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 5/23/2017 MDufilho 16 Figure 9.20 Comparison of energy sources used during short-duration exercise and prolonged-duration exercise. Short-duration exercise 6 seconds 10 seconds ATP stored in muscles is used first. ATP is formed from creatine phosphate and ADP (direct phosphorylation). 5/23/2017 MDufilho 30–40 seconds Prolonged-duration exercise End of exercise Glycogen stored in muscles is broken down to glucose, which is oxidized to generate ATP (anaerobic pathway). Hours ATP is generated by breakdown of several nutrient energy fuels by aerobic pathway. 17 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) 5/23/2017 MDufilho 18 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 5/23/2017 MDufilho 19 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 5/23/2017 MDufilho 20 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 5/23/2017 21 MDufilho 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 5/23/2017 MDufilho 22 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 5/23/2017 MDufilho 23