ANPS 19

1. ANPS 19 Skeletal Muscle Metabolism Dr. Tompkins Department of Neurological Sciences Given D408 john.tompkins@uvm.edu Reading: Anatomy & Physiology: An Integrative approach, McKinley et al., Chapter 10, Muscle Tissue, pages 350-354, 358-359 (Sections 10.4, 10.5, 10.8)

2. Outline • Supplying Energy for Skeletal Muscle Contraction • Oxygen Debt • Skeletal Muscle Fiber Types • Effects of Exercise and Aging on Skeletal Muscle • Exam

3. Skeletal Muscle Metabolism Learning Objectives: 1) Describe immediate, short-term, and long-term means that muscle fibers use to supply ATP for muscle contraction. • Explain how the means of supplying ATP is related to intensity and duration of exercise. • Define oxygen debt, and explain why it occurs.

4. Skeletal Muscle Metabolism: Supplying Energy for Skeletal Muscle Contraction Three ways to generate ATP in skeletal muscle fiber: • Immediate supply via the phosphagen system • Short-term supply via anaerobic cellular respiration • Long-term supply via aerobic cellular respiration Phosphatases -P Kinases +P

5. Phosphagen System (Figure 10.14) - Immediate ATP supply Myokinase Creatine kinase ATPase 2 ADP ADP + AMP ATP ADP + Pi ADP + CP ATP + Creatine CP ADP ADP ADP ATP Creatine kinase Myokinase ATPase Creatine Pi ADP AMP ATP ATP • Myokinasetransfers one phosphate from adenosine diphosphate (ADP) to another • ADP to yield ATP and AMP. • Generates an additional few secs of energy. • ATP already present in skeletal tissue hydrolyzed by (myosin)ATPaseinto ADP and Pi (phosphate ion). • Initial energy source good for about 5 sec maximal exertion. • Creatine phosphate (CP) cansupply ATP in skeletal muscle only. Creatine kinase transfers one phosphatefrom creatine phosphate to ADP to yield creatine and ATP. • Provides additional 10 to 15 seconds of energy. Process reversed during rest. (a) (b) (c) • The phosphagen system provides an immediate supply of ATP • Uses molecules containing phosphate • Not dependent upon presence of oxygen

6. Skeletal Muscle Metabolism: Supplying Energy for Skeletal Muscle Contraction • Short-term supply of ATP: anaerobic cellular respiration (glycolysis) • ATP provided by anaerobic cellular respiration • occurs in cytosol • does not require oxygen • glucose from glycogen or through the blood • converted to two pyruvate molecules • 2 ATP released per glucose molecule

8. Metabolic Processes for Generating ATP (Figure 10.15) Glycolysis Glucose NADH 2 ATP (a) Short-term energy supply (anaerobic cellular respiration) 2 pyruvate Insufficient oxygen Cytosol Lactic acid Outer mitochondrial membrane Oxygen Mitochondrion Pyruvate Outer membrane compartment Acetyl CoA NADH Inner mitochondrial membrane CO2 Mitochondrial matrix NADH CO2 Citric acid cycle FADH2 (b) Long-term energy supply (aerobic cellular respiration) ATP 2 e– H2O H+ e– O2 ATP 32 e– e– Electron transport chain ATP synthetase (oxidative phosphorylation) H+

9. Skeletal Muscle Metabolism: Supplying Energy for Skeletal Muscle Contraction • Long-term supply of ATP: aerobic cellular respiration (citric acid cycle + oxidative phosphorylation) • Occurs within mitochondria • Requires oxygen • Pyruvate oxidized to carbon dioxide • Transfer of chemical bond energy to NADH and FADH2 • Energy used to generate ATP by oxidative phosphorylation • 34 net ATP produced • Triglycerides also used for aerobic respiration and are the preferential fuel molecules for most skeletal muscle

10. Metabolic Processes for Generating ATP (Figure 10.15) Glycolysis Glucose NADH 2 ATP (a) Short-term energy supply (anaerobic cellular respiration) 2 pyruvate Insufficient oxygen Cytosol Lactic acid Outer mitochondrial membrane Oxygen Mitochondrion Pyruvate Outer membrane compartment Acetyl CoA NADH Inner mitochondrial membrane CO2 Mitochondrial matrix NADH CO2 Citric acid cycle FADH2 (b) Long-term energy supply (aerobic cellular respiration) ATP 2 e– H2O H+ e– O2 ATP 32 e– e– Electron transport chain ATP synthetase (oxidative phosphorylation) H+

11. Triglycerides also used for aerobic respiration and are the preferential fuel molecules for most skeletal muscle

12. ATP source dependent on intensity and duration of exercise(Figure 10.16) 50 meters: 5–6 seconds 1500 meters: 5–6 minutes 400 meters: 50–60 seconds Phosphagen system = immediate energy source Anaerobic cellular respiration = short-term energy source Aerobic cellular respiration = long-term energy source 1500-meter track

13. Skeletal Muscle Metabolism: Oxygen Debt When an individual participates in exercise during which the demand for oxygen exceeds the availability of oxygen, an oxygen debt is incurred. Oxygen debt isthe mount of additional oxygen that must be inhaled following exercise to restore pre-exercise conditions. Additional oxygen required to • replace oxygen on hemoglobin and myoglobin • replenish glycogen • replenish ATP and creatine phosphate in phosphagen system • convert lactic acid back to glucose (in the liver)

14. Skeletal Muscle Fiber Types Learning Objectives: 1) Explain the two primary criteria used to classify skeletal muscle fiber types. • Compare and contrast the three muscle fiber types. • Describe the distribution of muscle fiber types in a muscle and how this relates to function.

15. Skeletal Muscle Fiber Types Three types of skeletal muscle fibers • Slow oxidative fibers (slow, Type I) • Fast oxidative fibers (intermediate, Type IIa) • Fast glycolytic fibers (fast, Type IIb) Categorized based on • type of contraction (type of myosin ATPase) • means of supplying ATP

16. Skeletal Muscle Fiber Types: Criteria for Classification of Muscle Fiber Types Muscle Twitch Types of contraction generated • Fast-twitch fibers • have fast variant of myosin ATPase • short latent period • short contraction period • strong contraction • greater power and speed than slow-twitch fibers • Slow-twitch fibers • have slow variant of myosin ATPase • long latent period • long contraction period Latent period Relaxation period Contraction period Muscle tension Stimulus Time (msec)

17. Skeletal Muscle Fiber Types: Criteria for Classification of Muscle Fiber Types Means for supplying ATP • Oxidative fibers • use aerobic cellular respiration • have extensive capillaries, lots of mitochondria, lots of myoglobin (muscle oxygen transport protein - imparts red appearance) • contract for long periods (fatigue-resistant) • Glycolytic fibers • use anaerobic cellular respiration • have fewer structures needed for aerobic cellular respiration (white in appearance due to lack of myoglobin) • large glycogen reserves for anaerobic respiration • tire easily after short time of sustained activity (fatigable)

18. Three types of Skeletal Muscle Fibers (intermediate) (slow) (fast) Essentially everything you need to know about the three fiber types.

19. Skeletal Muscle Fiber Types: Distribution of Muscle Fiber Types Mixture of muscle fiber types in skeletal muscle • Variation in relative percentage of muscle fibers • Most muscles with a mixture of all types • E.g., in eye, high percentage of fast glycolytic fibers • requires swift, brief contractions • E.g., in postural muscles, high percentage of slow oxidative fibers • need to contract continually to help maintain posture

20. Skeletal Muscle Fiber Types: Distribution of Muscle Fiber Types Slow oxidative fibers (SO) Fast oxidative fibers (FO) Fast glycolytic fibers (FG) Mixture of muscle fiber types in skeletal muscle • Most muscles with a mixture of all types • Variation in relative percentage of muscle fibers • E.g., in eye, high percentage of fast glycolytic fibers • requires swift, brief contractions • E.g., in postural muscles, high percentage of slow oxidative fibers • need to contract continually to help maintain posture FO SO FO FO FG FG FO SO FG SO FO SO LM 40x FG Notice the difference in color of each fiber type

21. review - The Motor Unit Spinal cord Fig. 10.6a Motor neuron 1 Motor neuron 2 Muscle fibers innervated by motor neuron 1 • All fibers in a motor unit are of the same fiber type • Slow motor units contain slow fibers • Fast motor units contain fast fibers Neuromuscular junctions

22. Skeletal Muscle Fiber Types: Distribution of Muscle Fiber Types Muscle fiber types vary in individuals • Long distance runners • higher proportion of slow-oxidative fibers in legs • Sprinters • higher percentage of fast-glycolytic fibers • Determined primarily by genes • Determined partially by training FO SO FO FO FG FG FO SO FG SO FO SO LM 40x FG

23. Effects of Exercise and Aging on Skeletal Muscle Learning Objectives: 1) Compare and contrast the changes in skeletal muscle that occur as a result of an exercise program or from the lack of exercise. • Summarize the effects of aging on skeletal muscle.

24. Effects of Exercise and Aging on Skeletal Muscle: Effects of Exercise Changes in muscle from a sustained exercise program • Hypertrophy • increase in skeletal muscle size • results from repetitive stimulation of fibers • results in • more mitochondria • larger glycogen reserves • increased ability to produce ATP • more myofibrils that contain larger number of myofilaments • Hyperplasia • increase in the number of muscle fibers • may occur in a limited way with exercise

25. Effects of Exercise and Aging on Skeletal Muscle: Effects of Exercise Endurance training Little hypertrophy but major biochemical adaptations within muscle fibers. Increased numbers of mitochondria; concentration and activities of oxidative enzymes (e.g. succinate dehydrogenase, see below). Succinate dehy- drogenase (SDH) activity: Low activity light High activity dark Control 12-weeks treadmill running

26. Effects of Exercise and Aging on Skeletal Muscle: Effects of Exercise Disuse causes atrophy -- USE IT OR LOSE IT! Individual fiber atrophy (loss of myofibrils) with no loss in muscle fibers. Effect more pronounced in Type IIb fibers (Fast, white fibers). “Completely reversible” (in young healthy individuals). ATPase activity: Type I fibers light Type II fibers dark Prolonged bed rest Control

27. Clinical View: Anabolic steroids • Synthetic substances that mimic testosterone • Require prescription for legal use • Stimulate manufacture of muscle proteins • Popular performance enhancers • Side effects include • increased risk of heart disease and stroke • kidney damage and liver tumors • testicular atrophy, breast development in males • acne, high blood pressure, aggressive behavior • growth of facial hair and menstrual irregularities in women

28. Effects of Exercise and Aging on Skeletal Muscle: Effects of Aging Reduced capacity to recover from injury • Decreased number of satellite cells • Muscle mass often replaced by dense irregular connective tissue • termed fibrosis • decreases flexibility of muscle • can restrict movement and circulation • Reduced decline in muscular performance • with attention to physical fitness throughout life

29. Effects of Exercise and Aging on Skeletal Muscle: Effects of Aging Performance Declines with Aging despite maintenance of physical activity 100 80 60 Performance (% of peak) 40 Shotput/Discus Marathon 20 Basketball (rebounds/game) 0 20 30 40 50 60 10 Age (years) D.H. Moore (1975) Nature 253:264-265. NBA Register, 1992-1993 Edition

30. Motor unit remodeling with aging Central nervous system Muscle Motor neuron loss AGING • Fewer motor units • More fibers/motor unit

31. Effects of Exercise and Aging on Skeletal Muscle: Effects of Aging • Muscle injury may play a role in the development of atrophy and weakness with aging. • Muscles in old animals are more susceptible to contraction- induced injury than those in young or adult animals. (increased susceptibility to injury) • Muscles in old animals show delayed and impaired recovery following contraction-induced injury. (decreased ability to recover) • Following severe injury, muscles in old animals display prolonged, possibly irreversible, structural and functional deficits. (prolonged deficits)

32. EXAM • 80 questions total – 60 lecture + 20 lab • 60 lecture questions cover material in course manual – not responsible for additional slides • 6-8 questions per lecture (2-3 from each assessment quiz) • Good luck!