Chapter 9 & 24 Muscle Metabolism

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1 Chapter 9 & 24 Muscle Metabolism Annie Leibovitz/Contact Press Images

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. 10/7/2015 2

3 9.6 Energy for Contraction and ATP Providing Energy for Contraction ATP supplies the energy needed for the muscle fiber to: Move and detach cross bridges Pump calcium back into SR Pump Na + out of and K + back into cell after excitation-contraction coupling Available stores of ATP depleted in 4 6 seconds ATP is the only source of energy for contractile activities; therefore it must be regenerated quickly 10/7/2015 3

4 Providing Energy for Contraction ATP is regenerated quickly by three mechanisms: Direct phosphorylation of ADP by creatine phosphate (CP) Anaerobic pathway: glycolysis and lactic acid formation Aerobic respiration 10/7/2015 4

5 Figure 9.16a Pathways for regenerating ATP Direct phosphorylation during muscle activity. Coupled reaction of creatine phosphate (CP) and ADP Energy source: CP CP ADP Creatine kinase Creatine ATP Oxygen use: None Products: 1 ATP per CP, creatine Duration of energy provided: 15 seconds 10/7/2015 5

6 Figure 9.16b Pathways for regenerating ATP Anaerobic pathway during muscle activity. Glycolysis and lactic acid formation Energy source: glucose Glucose (from glycogen breakdown or delivered from blood) Glycolysis in cytosol 2 ATP net gain Released to blood Pyruvic acid Lactic acid O 2 O 2 Oxygen use: None Products: 2 ATP per glucose, lactic acid Duration of energy provided: seconds, or slightly more 10/7/2015 6

7 Providing Energy for Contraction (cont.) Anaerobic pathway: glycolysis and lactic acid formation (cont.) Lactic acid Diffuses into bloodstream Used as fuel by liver, kidneys, and heart Converted back into pyruvic acid or glucose by liver Anaerobic respiration yields only 5% as much ATP as aerobic respiration, but produces ATP 2½ times faster 10/7/2015 7

8 Anaerobic Glycolysis Fast pathway, but does not produce much ATP Important for the first 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 10/7/2015 8

9 Providing Energy for Contraction (cont.) Aerobic respiration Produces 95% of ATP during rest and light-tomoderate exercise Slower than anaerobic pathway Consists of series of chemical reactions that occur in mitochondria and require oxygen Breaks glucose into CO 2, H 2 O, and large amount ATP (32 can be produced) Fuels used include glucose from glycogen stored in muscle fiber, then bloodborne glucose, and free fatty acids Fatty acids are main fuel after 30 minutes of exercise 10/7/2015 9

10 Figure 9.16c Pathways for regenerating ATP Aerobic pathway during muscle activity. 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) Fatty acids Amino acids Pyruvic acid Aerobic respiration in mitochondria O 2 O 2 CO 2 H 2 O 32 ATP net gain per glucose Oxygen use: Required Products: 32 ATP per glucose, CO 2, H 2 O Duration of energy provided: Hours 10/7/

11 Oxidation of Glucose (cont.) Citric acid cycle Also called Krebs cycle Occurs in mitochondrial matrix Fueled by pyruvic acid from glucose breakdown and fatty acids from fat breakdown 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 10/7/

12 Oxidation of Glucose (cont.) Citric acid cycle (cont.) Transitional phase is where each pyruvic acid is converted to acetyl coenzyme A (acetyl CoA) in three steps Each acetic acid is decarboxylated and oxidized, generating: 3 NADH + H + 1 FADH 2 2 CO 2 1 ATP 10/7/

13 Figure 24.7 Simplified version of Electron Glycolysis Citric acid transport chain Carbon atom cycle and oxidative phosphorylation the citric (Krebs) P i Inorganic phosphate cycle. CoA Coenzyme A ATP ATP ATP Cytosol Pyruvic acid from glycolysis Mitochondrion (matrix) Transitional phase CO 2 NAD + CoA NADH + H + Acetyl CoA Oxaloacetic acid Citric acid NADH + H + (pickup molecule) CoA (initial reactant) NAD + Malic acid Isocitric acid Citric acid cycle CO 2 NAD + NADH + H + FADH 2 Fumaric acid CO 2 a-ketoglutaric acid CoA NAD + FAD Succinic acid Succinyl-CoA NADH + H + CoA GTP GDP + P i ADP ATP 10/7/

14 Summary of ATP Production Complete oxidation of 1 glucose molecule Totals between substrate-level phosphorylation and oxidative phosphorylation equal 32 ATPs Glycolysis + Krebs cycle + electron transport chain But.energy is required to move NADH + H + generated in glycolysis into mitochondria, which uses up ~2 ATPs, so final total is 30 ATPs produced There is still uncertainty on final total 10/7/

15 Figure Energy yield during cellular respiration. Cytosol 2 NADH + H + Mitochondrion Electron shuttle across mitochondrial membrane 2 NADH + H + 6 NADH + H + 2 FADH 2 Glucose Glycolysis Pyruvic acid 2 Acetyl CoA Citric acid cycle Electron transport chain and oxidative phosphorylation (4 ATP 2 ATP used for activation energy) 10 NADH + H ATP 2 FADH ATP Net +2 ATP by substrate-level phosphorylation +2 ATP + about 28 ATP by substrate-level phosphorylation by oxidative phosphorylation 2 ATP (average shuttle cost) About 30 ATP Typical ATP yield per glucose 10/7/

16 Providing Energy for Contraction (cont.) Energy systems used during sports Aerobic endurance Length of time muscle contracts using aerobic pathways Light-to-moderate activity, which can continue for hours Anaerobic threshold Point at which muscle metabolism converts to anaerobic pathway 10/7/

17 Figure 9.17 Comparison of energy sources used during short-duration exercise and prolongedduration exercise. Short-duration, high-intensity exercise Prolonged-duration exercise 6 seconds 10 seconds seconds End of exercise Hours ATP stored in muscles is used first. 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 is generated by breakdown of several nutrient energy fuels by aerobic pathway. 10/7/

18 Muscle Fatigue Physiological inability to contract despite continued stimulation Usually occurs when there are ionic imbalances Levels of K +, Ca 2+, P i can interfere with E-C coupling Prolonged exercise may also damage SR and interferes with Ca 2+ regulation and release Lack of ATP is rarely a reason for fatigue, except in severely stressed muscles 10/7/

19 Excess Postexercise Oxygen Consumption For a muscle to return to its pre-exercise state: Oxygen reserves are replenished Lactic acid is reconverted to pyruvic acid Glycogen stores are replaced ATP and creatine phosphate reserves are resynthesized All replenishing steps require extra oxygen, so this is referred to as excess postexercise oxygen consumption (EPOC) Formerly referred to as oxygen debt 10/7/

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 10/7/

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 10/7/

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 Ca 2+ entry damaged contractile fibers inflammatory cells muscle mass drops Victims become clumsy and fall frequently; usually die of respiratory failure in 20s 10/7/

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 10/7/

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