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.
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4/14/2017

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
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4. Muscle Metabolism: Energy for Contraction
ATP regenerated by:
Direct phosphorylation of ADP by creatine phosphate (CP)
Anaerobic pathway (glycolysis  lactic acid)
Aerobic respiration
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5. Direct phosphorylation
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
4/14/2017
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6. Anaerobic pathway Glycolysis and lactic acid formation
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
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7. At 70% of maximum contractile activity
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
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8. Fast pathway, but does not produce much ATP
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
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9. Produces 95% of ATP during rest and light to moderate exercise; slow
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
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10. Aerobic cellular respiration
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
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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
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4/14/2017

12. 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
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13. Pyruvic acid from glycolysis
Figure Simplified version of the Krebs (citric acid) cycle.
Glycolysis
Krebs
cycle
Electron trans-
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)
Malic acid
Isocitric acid
Krebs cycle
Fumaric acid
α-Ketoglutaric acid
Succinic acid
Succinyl-CoA
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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
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15. Figure 24.12 Energy yield during cellular respiration.
Mitochondrion
Cytosol
Electron
shuttle across
mitochondrial
membrane
Glycolysis
Electron transport
chain and oxidative
phosphorylation 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
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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
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17. Figure Comparison of energy sources used during short-duration exercise and prolonged-duration exercise.
Short-duration exercise
Prolonged-duration exercise
6 seconds
10 seconds
30–40 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.
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18. Physiological inability to contract despite continued stimulation
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)
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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
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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
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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
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4/14/2017

22. 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
4/14/2017
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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
4/14/2017
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