Skeletal Muscle Physiology and ATP Production
Muscle Cells and ATP Requirements
Muscle cells require ATP for multiple purposes:
Active transport processes
Metabolic processes
Muscle contraction
Summary of ATP requirements for muscle contraction:
Detachment of myosin from actin (cross-bridge detachment)
Re-energizing the myosin head (transitioning it from low-energy to high-energy form)
Actively pumping Ca$^{2+}$ back into the sarcoplasmic reticulum after it has been released
Muscle Metabolism and ATP Production
Skeletal muscle produces ATP in three distinct ways:
Creatine phosphate pathway
Anaerobic pathway (lactic acid fermentation)
Aerobic cellular respiration
Note: Most body cells carry out aerobic respiration; however, red blood cells (RBCs) do not perform this pathway.
Creatine Phosphate Pathway
For activities lasting longer than approximately 15 seconds, muscles metabolize nutrients to generate ATP.
In the creatine phosphate pathway:
Phosphate is transferred from creatine phosphate to ADP, producing ATP:
Reaction: Creatine phosphate + ADP → creatine + ATP
This reaction is catalyzed by creatine kinase, an enzyme found in skeletal, cardiac, and smooth muscle.
Elevated creatine kinase levels in the blood can indicate muscle damage, such as after a heart attack.
This pathway is sufficient for short bursts of activity, like a 100m dash.
Anaerobic Pathway (Lactic Acid Fermentation)
The anaerobic pathway utilizes glucose (but not free fatty acids - FFAs) and provides energy for approximately 30-40 seconds of maximal muscle activity.
Key characteristics:
Yields 2 ATP per glucose
Does not require oxygen
The primary tissue that utilizes this pathway is skeletal muscle.
Advantages and Limitations of Anaerobic Pathway
Advantages:
Quick energy production.
Limitations:
Requires a larger amount of glucose to produce the same amount of ATP as the aerobic pathway.
Can lead to acidosis:
Decreased pH inhibits enzymes in glycolysis, decreases ATP production, and contributes to muscle soreness.
However, liver, heart, and kidney cells can utilize some lactic acid as fuel, and the liver can convert lactic acid into glucose, helping to remove some acid from the blood.
Aerobic Cellular Respiration
Aerobic cellular respiration:
Accounts for 90-95% of ATP used by muscle at rest and during light to moderate exercise.
Yields 30-32 ATP per glucose.
Commonly occurs during endurance exercises such as long-distance running and swimming.
Nutrient Sources for ATP Production
Both anaerobic and aerobic pathways require nutrients:
Anaerobic pathway: Utilizes glucose.
Aerobic metabolism: Can use both glucose and lipids (free fatty acids = FFAs).
Sources of Glucose and FFAs in the Body
Circulation:
Glucose and free fatty acids travel in the blood and are transported into muscle cells.
Storage Forms:
Liver and skeletal muscle: Store glycogen, which can be broken down into glucose and released into the blood.
Adipose tissue: Stores triglycerides, which can be broken down into FFAs and glycerol, subsequently released into the blood.
Aerobic Metabolism Details
Aerobic metabolism requires oxygen, and the overall equation for aerobic cellular respiration is:
C$6$H${12}$O$6$ (glucose) + 6 O$2$ → 6 CO$2$ + 6 H$2$O
The energy released from this pathway is utilized to synthesize ATP.
Important to note the inputs (glucose and oxygen) and outputs (carbon dioxide and water), though full equation memorization is not required.
Stages of Cellular Respiration
There are three stages of cellular respiration (aerobic metabolism) per glucose metabolized aerobically, yielding 30-32 ATP.
Metabolizing Lipids for ATP Production
Triglycerides stored in cells can be broken down into fatty acids and glycerol, which can be utilized in aerobic respiration.
A 16-carbon fatty acid can yield 129 ATP.
Excess fat metabolism may lead to a buildup of ketone bodies, which are acidic and can result in acidosis.
Metabolizing Proteins for ATP Production
Proteins (amino acids) are not typically the primary fuel for ATP production.
When metabolized, keto acids are produced, which may result in acidosis.
Utilization of Pathways by Muscle
No pathway is completely shut off; the percentage of ATP derived from each pathway shifts based on:
Duration of activity
Activity intensity level
At rest:
Almost all ATP is derived from the aerobic pathway.
During exercise:
At the beginning, stored ATP, creatine phosphate, and lactic acid pathways provide 100% of the ATP required.
As the duration of exercise increases, the proportion of ATP produced aerobically rises, with 90-95% of ATP used by muscles during light to moderate exercise generated via the aerobic pathway.
As exercise intensity increases, the percentage of ATP produced anaerobically (via lactic acid fermentation) also increases.
Fuel Usage by Muscles
In muscles at rest:
~66% of ATP is derived from lipid metabolism.
~33% of ATP is derived from carbohydrate metabolism.
In muscles during exercise:
Initial spike in carbohydrate usage occurs at the onset of exercise.
Over longer durations, there is a mixture of lipid and carbohydrate metabolism.
As exercise intensity escalates, carbohydrate metabolism increases while lipid metabolism diminishes.
Summary of Energy Production in Exercise
Short-duration exercise:
1-3 seconds: ATP stored in muscles is utilized first.
10 seconds: ATP is formed from creatine phosphate and ADP (direct phosphorylation).
30-40 seconds: Glycogen stored in muscles is broken down to glucose and oxidized to generate ATP (anaerobic pathway).
End of exercise (hours): ATP generated by the breakdown of several nutrient energy fuels via the aerobic pathway.
Types of Muscle Fibers
Two main characteristics used to describe muscle fibers:
Speed of contraction:
Slow fibers (slow twitch): Myosin heads split ATP more slowly.
Fast fibers (fast twitch)
Major pathway for ATP synthesis:
Oxidative fibers: Rely on aerobic cellular respiration.
Glycolytic fibers: Rely on anaerobic glycolysis.
Structural and Functional Characteristics of Muscle Fibers
Three types of skeletal muscle fibers:
Slow oxidative fibers
Speed of contraction: Slow
Myosin ATPase activity: Slow
Primary pathway: Aerobic
Myoglobin content: High
Glycogen stores: Low
Rate of fatigue: Slow (fatigue-resistant)
Best suited for endurance-type activities (e.g., running marathons).
Fast oxidative fibers
Speed of contraction: Fast
Myosin ATPase activity: Fast
Primary pathway: Aerobic (some anaerobic)
Myoglobin content: High
Glycogen stores: Intermediate
Rate of fatigue: Intermediate (moderately fatigue-resistant)
Best suited for activities such as sprinting and walking.
Fast glycolytic fibers
Speed of contraction: Fast
Myosin ATPase activity: Fast
Primary pathway: Anaerobic glycolysis
Myoglobin content: Low
Glycogen stores: High
Rate of fatigue: Fast (fatigable)
Best suited for short-term, high-intensity movements (e.g., hitting a baseball).
Muscle Fatigue
Muscle fatigue is defined as the physiological inability to contract, meaning the muscle cannot respond to stimuli.
This differs from central fatigue, which refers to the feeling of tiredness and the desire to cease activity originating from the central nervous system.
Mechanisms of fatigue are not completely understood, but for focused study:
Fatigue from intense, short-duration exercise is likely due to ionic imbalances that reduce Ca$^{2+}$ release from the sarcoplasmic reticulum (SR).
Fatigue from prolonged, low-intensity exercise likely stems from:
Structural damage to SR, impacting Ca$^{2+}$ release.
Glycogen depletion.
Metabolite accumulation.
Effects of Exercise on Skeletal Muscle
Endurance exercise:
Transforms some fast glycolytic fibers into fast oxidative fibers.
Weight training:
Increases the size of fast glycolytic fibers, a process known as hypertrophy, which refers to an increase in the size of muscle fibers due to enhanced actin/myosin synthesis within these fibers.
Atrophy:
Refers to the loss of muscle mass due to disuse or injury, but if the nerve supply to the muscles is intact and healthy, atrophy is reversible.