Transcript Lecture 4 - Muscle Metabolism

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.
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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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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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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
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Oxygen use: None
Products: 1 ATP per CP, creatine
Duration of energy provided:
15 seconds
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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
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Pyruvic acid
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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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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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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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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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
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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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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
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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
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α-Ketoglutaric acid
Succinyl-CoA
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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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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
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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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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).
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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.
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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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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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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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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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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
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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
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