Muscle Metabolism: ATP & Energy Systems

Key Metabolic Pathways in Skeletal Muscle

• Adenosine Triphosphate (ATP) is the only energy source used directly by muscles for contractile activities
• ATP production demand and mechanism vary based on the type of work
• A muscle cell contains a small store of ATP at rest
• This ATP store will only last about 3 seconds once contracting begins, therefore it needs to be regenerated

ATP Regeneration

• Stored ATP gets used almost immediately at the start of exercise within a few seconds
• ATP gets regenerated from ADP:
  • Direct phosphorylation of ADP by creatine phosphate (CP)
  • Anaerobic pathway with glycolysis producing lactic acid
  • Aerobic respiration of fatty acids in the mitochondria, which is a slow process, used for low intensity

Energy System Interaction

• ATP/PCr system provides energy for roughly 15 seconds
• Anaerobic glycolysis provides energy from rougly 15-120 seconds
• Oxidative system provides energy for >120 seconds

Phosphocreatine-Creatine System

• Formed from amounts of cell ATP + CP
• Together provide maximal muscle power for 8-10 seconds
• Enough energy is provided for a 100 meter run
• Phosphagen system is useful for maximal short bursts of muscle power (8-10 seconds)
• Severe exercise for short duration
• Product: 1 ATP
• Energy of muscle CP is immediately available for contraction as energy of ATP
• Oxygen use: None
• Products: 1 ATP per CP, creatine
• Duration of energy provided: 15 seconds

Anaerobic Glycolysis (Glycogen-Lactic acid system) Without Oxygen

• Primary energy source for peak (sever) muscular activity
• Provides 1.3-1.6 minutes of maximal muscle activity
• The process of anaerobic metabolism can maintain ATP supply for about 45-60s
• Source of energy: Carbohydrate (glycolysis) , Lactate and ATP
• Produces 2 ATP molecules per molecule of glucose + 2 NADH
• Lactic acid diffuses out of muscles > blood > taken by the liver > Glucose
• (by gluconeogenesis) > blood >taken by the muscle again.

Anaerobic Glycolysis (Glycogen-Lactic acid system)

• Anaerobic metabolism is inefficient
• Large amounts of glucose are used for very small ATP returns
• Lactic acid is produced, and its presence contributes to muscle fatigue
• Sports that require bursts of speed and activitiy, such as basketball and tennis, use anaerobic metabolism

Aerobic Metabolism (With Oxygen)

• Primary energy source of resting muscles
• Converts glucose into glycogen
• Creates energy storage compounds as CP
• During rest and light to moderate exercise, aerobic metabolism contributes 95% of necessary ATP
• Breaks down fatty acids, pyruvic acid (made via glycolysis), and amino acids
• Produces 36 ATP molecules per glucose molecule
• Source of energy: mainly fatty acids, then carbohydrate, amino acids

Oxygen Debt

• Amount of extra O2 that must be taken after exercise to restore the muscles to the resting conditions
• Excess oxygen intake serves many tasks:
  • Replenishes the oxygen stored by myoglobin and hemoglobin
  • Converts remaining lactic acid back into glucose
  • Used for aerobic metabolism to make ATP:
    • Replenishes the phosphagen system
    • Replenishes the glycogen stores
    • Powers the Na+/K+ pump to restore resting ionic conditions within the cell

Muscle Fatigue

• Physiological inability to contract
• Results primarily from a relative deficit of ATP
• Other contributing factors include:
  • Decrease in sarcoplasmic pH
  • Increased sarcoplasmic [ADP]
  • Ionic imbalances
• Occurs due to prolonged strong contractions
• Results from inability of the contractile & metabolic process of the muscle fibers to continue supplying the same work output
• Interruption of blood flow or decrease oxygen supply lead to rapid fatigue.

Muscle Fatigue Causes and Results

• Causes of fatigue:
  • Depletion of muscle glycogen or ATP
  • Depletion of acetyl choline stores at the nerve terminal
  • Accumulation of metabolites as lactic acid
• Results of Muscle Fatigue:
  • Depletion of metabolic reserves
  • Damage to sarcolemma and sarcoplasmic reticulum
  • Low pH (lactic acid)
  • Muscle exhaustion and pain

Central Fatigue

• Describes the uncomfortable feelings that come from being tired, often called "psychological fatigue"
• Arises from factors released by the muscle during exercise that signal the brain to feel tired
• Psychological fatigue precedes peripheral fatigue and occurs well before the muscle fiber can no longer contract
• One of the outcomes of training is to learn how to overcome psychological fatigue

Types of Contractions

• Contractions can be:
  • Isometric: Iso= same, metr=measure
  • Isotonic: Iso=same, ton=tension

Isotonic Contraction Experiment

• Hang a 3kg weight from that muscle and stimulate it -> muscle will shorten
• Before shortening, cross-bridges produce tension to overcome the 3kg resistance, so internal tension rises until external tension in tendon exceeds the amount of resistance
• As muscle shortens, internal and external tensions remain constant at a value just exceeding the resistance

Isotonic Contractions

• Tensions (effort) increase and muscle fibers shorten and lenghten
• Example: lifting dumbbells with arm
• Concentric Contraction: Tension (effort) exceeds resistance (weight), and muscle shortens
• Eccentric contraction: resistance exceeds tension (effort) and muscle lengthens (due to gravity)

Isometric Contractions

• The muscle as a whole does not change length, and the tension produced never exceeds the resistance
• To the same muscle as before, we attach a 6kg weight
• Although cross-bridges form and tension rises to peak values, the muscle cannot overcome the resistance of the weight and cannot shorten
• Although the muscle as a whole does not shorten, the individual fibers shorten until the tendons are taut, and the external tension equals the internal tension
• The muscle fibers cannot shorten further because the external tension does not exceed the resistance

Isometric Contractions Details

• Example: pushing against a wall
• Tension (effort) never exceeds resistance (weight)
• Muscle does NOT change length

Contraction Comparison

• Isotonic contraction:
  • Tension: Constant
  • Length: Decreases
  • Work done: Present
  • Duration: Longer
  • Energy needed: More
  • Energy of contraction: Converted to external work and waste heat
  • Example: Contraction of biceps to lift an object
• Isometric contraction:
  • Tension: Rises markedly
  • Length: Constant
  • Work done: No
  • Duration: Shorter
  • Energy needed: Less
  • Energy of contraction: Converted to waste heat
  • Example: Contraction of quadriceps to stiff the Knee

Muscle Fiber Types

• 2 main types:
  • Slow fibers
  • Fast fibers

Slow Fibers

• Contracts slowly because its myosin ATPases work slowly
• Depends on oxygen delivery and aerobic metabolism
• Is fatigue resistant and has high endurance
• Is thin in diameter, and a large amount of cytoplasm impedes O2 and nutrient diffusion
• Cannot develop high tension because small diameter means few myofibrils
• Has rich capillary supply and lots of mitochondria
• Contains lots of the O2-storing protein, myoglobin, which gives it a red color
• Uses lipids, carbs, and amino acids as substrates for it aerobic metabolism
• Best suited for endurance type activities
• Called red fibers, slow oxidative fibers, type I fibers

Fast Fibers

• Contracts in 0.01 seconds or less after stimulation
• Large in diameter, contain densely packed myofibrils, large glycogen reserves, and relatively few mitochondria
• Able to develop great tension because contains a large number of sarcomeres
• Uses ATP in massive amounts, and is supported by anaerobic metabolism
• Fatigue rapidly
• Fast fatigue (FF) fibers, fast glycolytic (FG) fibers, white fibers
• Best suited for short term, power activities

Fast vs Slow Twist Muscles

• Fast Twitch Fibers
  • Most skeletal muscle fibers
  • Contract in 0.01 sec or less after stimulation
  • Large in diameter
  • Contain densely-packed myofibrils
  • Have large glycogen reserves & few mitochondria
  • Produce powerful contractions
  • Fatigue rapidly
  • “white muscle fibers”
• Slow Twitch Fibers
  • ~Half the diameter of fast fibers
  • Take 3x as long to contract after stimulation
  • Specialized to continue contracting for extended periods
  • Contain extensive network of capillaries & has higher oxygen supply
  • Contain red pigment myoglobin
  • Contain more mitochondria than fast fibers
  • “red muscle fibers”

Muscle Fiber Comparison

• Fast fibers (White fibers):
  • Fiber size: Larger
  • Innervation: Larger nerve fiber
  • Glycolytic enzymes: Larger amount
  • S. Reticulum: Extensive (Rapid calcium release)
  • Blood supply: Less extensive
  • Mitochondria: Fewer
  • Myoglobin: Small amount
  • Contraction: Adapted for very rapid intense contraction for short period (depends on anaerobic metabolism)
  • Fatigue: Rapid
  • Example: Ocular muscle
• Slow fibers (Red Fibers):
  • Fiber size: Smaller
  • Innervation: Smaller
  • Glycolytic enzymes: Smaller
  • S. Reticulum: Less extensive
  • Blood supply: More extensive
  • Mitochondria: Increased number
  • Myoglobin: Large amount
  • Contraction: Adapted for slow continuous muscle activity (depends on aerobic metabolism)
  • Fatigue: Delayed
  • Example: Soleus muscle

Cramp Important Terms

• A prolonged spasm that causes the muscle to become taut and painful
• Associated with repeated firing of action potentials in the motor neurons
• Found most commonly in muscles of the leg, especially the lower leg and foot
• The cramp may be either central or peripheral
• The central theories suggest that there are some changes in the brain or spinal cord that cause an abnormal frequency of action potentials to the lower motor neurons that will innervate skeletal muscle
• Peripheral theories suggest that there is some change around peripheral motor neurons that cause them to discharge spontaneously

Atrophy Important Terms

• Reduction in size of a cell, tissue, or organ
• In muscles, often caused by disuse

Hypertrophy Important Terms

• Increase in size of a cell, tissue or an organ
• In muscles, hypertrophy of the organ is always due to cellular hypertrophy (increase in cell size) rather than cellular hyperplasia (increase in cell number)
• Muscle hypertrophy occurs due to the synthesis of more myofibrils and synthesis of larger myofibrils

Fibrosis Important Terms

• Replacement of normal tissue with heavy fibrous connective tissue (scar tissue)

Tetanus

• Many toxins, drugs & diseases may interfere with events occurring at the neuromuscular junction
• Infection of Nervous System from potentially deadly bacteria Clostridium tetani
• Bacteria spreads & makes poison called tetanospasmin
• The toxin enters peripheral nerve endings, binds there irreversibly, then travels retrograde along the axons and synapses, and ultimately enters the central nervous system (CNS)
• Release of inhibitory transmitters from nerve terminals is blocked, thereby causing unopposed muscle stimulation by acetylcholine and generalized tonic spasticity
• Spasms can be so powerful that they tear the muscles or cause fractures of the spine