Control of Fuel Selection in Muscles

Control of Fuel Selection in Muscles

Biochemistry team

Academic Year: 2025/2026

Aim

  • To show how muscles select their fuel based on various factors, including:

    • Type of muscle

    • Fed and fasting state

    • Degree of exercise intensity

    • Training effects

Objectives

After this lecture, you should be able to:

  • Distinguish between the types of muscle and their fuels.

  • Relate the impact of the fed versus fasting state on muscle fuel selection.

  • Classify the effect of exercise intensity on muscle fuel usage.

  • Identify how training affects fuel selection in muscles.

Why are there Different Types of Skeletal Muscle Fibers?

  • The body has diverse requirements for its skeletal muscles, including:

    • Generating rapid movements in some cases.

    • Maintaining high levels of tension without fatigue in others.

    • Some muscles exhibit mixed properties.

Types of Skeletal Muscle Fibers

  • The two main types of skeletal muscle fibers are:

    1. Type I fibers (Red / Slow twitch fibers):

    • Have a high rate of citric acid cycle activity.

    • Rich in mitochondria, myoglobin, and intramuscular triacylglycerol.

    1. Type II fibers (White / Fast twitch fibers):

    • Have a low rate of citric acid cycle activity.

    • Poor in mitochondria and myoglobin; higher muscle glycogen content.

Examples of Muscle Fiber Functionality

I. Soleus Muscle

  • Key roles include:

    • Maintaining posture (e.g., while standing).

    • Contributing to leg movement.

  • Characteristics:

    • An endurance muscle capable of constant use for hours.

    • Reaches peak tension in 80-200 minutes (slow kinetics).

    • Contains predominantly slow contracting muscle fibers.

II. Extra-Ocular Eye Muscles

  • Characteristics:

    • Control eye movement and elevate the eyelid.

    • Produce rapid, intermittent movements without maintaining tension for long periods.

    • Reaches peak tension in 7-8 minutes (fast kinetics).

    • Contain predominantly fast contracting muscle fibers.

Types of Exercise

  • Aerobic Exercise:

    • Sustained for long periods, typically low to moderate intensity.

    • Example: Marathon running.

  • Anaerobic Exercise:

    • Short duration, high intensity.

    • Example: Weightlifting or sprinting.

Muscle Fuel Selection

  • Analogy comparing muscles and motorbikes:

    • Both convert chemical energy into motion.

    • Motorbike engine uses petrol; muscles use food-derived chemical energy.

  • Muscles can utilize various fuels based on:

    1. Intensity of work (high vs. low intensity).

    2. Fed state or fasting state of the individual.

ATP: The Energy Form in Living Cells

  • Source of Energy:

    • ATP (adenosine triphosphate) powers the contraction of working muscles.

    • Energy comes from carbohydrates, fats, and proteins.

Sources of Fuel for Muscles

  1. Plasma Glucose: Utilized during the fed state (exercise or rest).

  2. Muscle & Liver Glycogen: Resulting from glycogenolysis during fasting (<18 hrs) and high-intensity exercise.

    • Exhaustion coincides with depletion of muscle glycogen.

  3. Muscle & Adipose Fat (TAG): Used during fasting and low-intensity exercise.

  4. Plasma Lipoproteins & NEFA: Utilized during fasting and non-exercising states.

  5. Ketone Bodies: Used during prolonged exercise or extended fasting.

  6. Amino Acids: Derived from degraded muscle tissue during starvation.

Fuel Sources Summary

Fed State vs. Fasting State

  • Fed State:

    • External sources of fuel.

  • Fasting State:

    • Internal sources of fuel.

    • Prolonged fasting: muscle uses amino acids by degrading proteins.

  • Resting states versus exercising states considerably influence available fuel sources.

Fuel Type by Activity

  • Muscle generally uses a mix of carbohydrate and fat depending on:

    • Fed state and high intensity exercise predominate carbohydrate usage (glucose).

    • Fasting shifts to glycogen, TAGs, and KBs.

    • Prolonged starvation leads to reliance on amino acids for energy.

Fuel Choice during the Fed-Starve Cycle

I. The Fed State

  • Leads to insulin secretion, which regulates metabolism:

    • Stimulates fuel storage and protein synthesis.

    • Increases:

    • Glycogenesis

    • Glycolysis

    • Lipogenesis

    • Decreases:

    • Gluconeogenesis

    • Lipolysis.

  • Insulin promotes glucose uptake and inhibits fatty acid oxidation.

II. The Early Fasting State

  • Blood glucose levels drop, leading to:

    • Decreased insulin secretion.

    • Increased glucagon secretion, mobilizing glycogen stores.

  • Glucagon's Action:

    • Stimulates:

    • Glycogenolysis

    • Gluconeogenesis

    • Inhibits:

    • Glycogenesis

    • Lipogenesis

    • Glycolysis.

Fuel Choice During Exercise

  • Determined by intensity and duration:

    • At rest: Uses external fuel sources (blood glucose, TAG).

    • During exercise: Primarily internal sources (muscle glycogen, TAG).

    • High-intensity exercise favors blood glucose.

Energy for Muscle Contraction

  • Myosin converts chemical energy (ATP) to muscle contraction movements.

  • Muscle ATP is limited; therefore:

    • The rate of ATP production becomes crucial for physical activities.

ATP Replenishment Methods in Muscles

  1. Adenylate Kinase

  2. Creatine Kinase (Phosphokinase)

  3. Glycolysis

  4. Fatty Acid Oxidation

  5. TCA Cycle & Electron Transport Chain (ETC)

  • These methods work together dynamically depending on exercise phase and intensity.

Phases of ATP Production (Energy Systems)

  1. ATP/Creatine Phosphate:

    • Lasts ~3 seconds (immediate energy source).

    • Creatine Phosphate (CP) lasts 8-10 seconds, providing energy rapidly.

  2. Glycogen & Glucose (Anaerobic):

    • Provides energy for ~90 seconds without oxygen but produces lactic acid.

  3. Aerobic Respiration:

    • After 2 minutes, oxygen becomes available, utilizing stored energy for extended periods (hours).

Practical Example of Fuel Usage

  • Scenario: Running to a hospital for an emergency.

    • Initial 3 seconds: Muscle cells utilize stored ATP.

    • Next 8-10 seconds: Muscles use creatine phosphate.

    • Following 90 seconds: The glycogen system (anaerobic respiration) kicks in.

    • Afterwards: Aerobic respiration takes over.

Metabolic Fuel Use over Time

  • Significant changes in energy source with exercise duration:

    • Stored ATP and creatine phosphate utilized first, followed by anaerobic metabolism, and finally aerobic metabolism for extended duration.

Specifics of Energy Systems in Exercise

  • Sprinters (e.g., 100m) utilize ATP/creatine phosphate for short bursts.

  • Middle-distance events (200m, 400m) rely on anaerobic glycolysis.

  • Long-distance events (marathons) depend on aerobic respiration.

Muscle Metabolism During Exercise

  • Increased glycogenolysis and glucose uptake during activity.

  • Increased uptake of fatty acids and TAG breakdown.

  • Elevated adrenaline levels stimulate glucose release and fatty acid mobilization.

Low to Moderate Intensity Exercise

  • At lower intensity levels, oxidative metabolism can adequately produce ATP, preferentially utilizing fatty acids for energy due to the precious nature of glucose.

Fatty Acid Mobilization During Exercise

  • Release of triacylglycerols (TAG) from adipose tissue and muscle is crucial.

  • Controlled by adrenaline secretion, leading to increased FFAs for mitochondrial oxidation during exercise.

Acetyl CoA and Glucose Metabolism

  • Increased fatty acid usage generates acetyl CoA, inhibiting glucose metabolism.

  • Results in slowed glycogen usage and delayed exhaustion onset.

Respiratory Quotient (RQ)

  • RQ is crucial for calculating basal metabolic rate (BMR) based on CO₂ production and O₂ consumption.

  • RQ values indicate which macronutrient is being metabolized:

    • 0.7 for fats

    • ~0.8 for proteins

    • 1.0 for carbohydrates

  • A mixed diet approximates an RQ of 0.8, indicating the balance of fuel sources used.

Effects of Training on Fuel Usage

  • Anaerobic Training Effects:

    • Increased size of Type II fibers, enhancing muscle bulk and glycogen storage.

  • Aerobic Training Effects:

    • Increased glycogen synthase activity and capillary density.

    • Enhanced expression of fatty acid transport proteins and mitochondrial dimension.

    • Temporary and reversible changes.

Consequences of Inactivity on Muscle Metabolism

  • Severe immobilization can drastically reduce mitochondrial counts and power generation capabilities.

  • Mitochondrial functionality drops as a result of muscle disuse.

Summary of Fuel Metabolism Impacts

  • Muscle metabolism is affected by multiple factors including:

    • Fed vs. fasting state.

    • Intensity and duration of exercise.

    • Training status.

  • Regulation of glucose and fatty acid availability and utilization is crucial in dictating muscle fuel selection.

Suggested Readings

  • Chapter 20, Biochemical, Physiological & Molecular Aspects of Human Nutrition (ed. by Martha Stipanuk)

  • Section 30.4, Fuel Choice During Exercise Is Determined by Intensity and Duration of Activity. Biochemistry, 5th edition. Berg JM, Tymoczko JL, Stryer L. New York: W H Freeman; 2002.

  • Use of endogenous carbohydrate and fat as fuels during exercise. Proceedings of the Nutrition Society, 57: 49-54. Cited by Martin WH & Klein S (1998).

  • Principles of Exercise Biochemistry, J. R. Poortmans (Ed.). (Karger, 1988), pp. 78–119.

  • Fat Metabolism During Exercise: New Concepts. Edward F. Coyle, Ph.D., Sports Nutrition; 2006.