Bioenergetics and Metabolism Notes

Unit I Bioenergetics & Metabolism Overview

• Homeostasis
• Principles of Adaptation
• Bioenergetics: The transfer of energy
• Thermodynamics
• Systems of energy production
• Metabolic processes
• Substrate Utilization
• Exercise metabolism

Understanding Graphs

• Independent variable: What is controlled (e.g., exercise intensity).
• Dependent variable: Dependent on the independent variable (e.g., heart rate changes as a function of exercise intensity).

Homeostasis: Dynamic Constancy

• Maintenance of a constant and “normal” internal environment.
• Steady state: Physiological variable is unchanging but not necessarily “normal.”
• Balance between demands placed on the body and the body’s response to those demands.
• Examples include body core temperature and arterial blood pressure.

Biological Control System

• Series of interconnected components that maintain a physical or chemical parameter at a near-constant value.
• Three components:
  • Sensor or receptor: Detects changes in variable.
  • Control center: Assesses input and initiates a response.
  • Effector: Changes the internal environment back to normal.

Examples of Homeostatic Control

• Regulation of body temperature:
  • Thermal receptors send a message to the brain.
  • Response by skin blood vessels and sweat glands regulates temperature.
  • Negative feedback mechanism regulates body temperature around a set point of 37^o C.
• Regulation of blood glucose:
  • Function of the endocrine system, requiring the hormone insulin.
  • Elevated blood glucose signals the pancreas to release insulin.
  • Insulin causes cellular uptake of glucose, lowering blood glucose levels.
  • The pancreas acts as both the sensor and effector organ.

Exercise as a Test of Homeostatic Control

• Exercise disrupts homeostasis by changes in pH, O2, CO2, energy stores, and temperature.
• Control systems maintain steady state during submaximal exercise in a cool environment.
• Intense or prolonged exercise in a hot/humid environment may exceed the ability to maintain homeostatic/steady-state control, leading to fatigue and cessation of exercise.
• Exercise training improves homeostatic control via cellular adaptation.

Exercise-Induced Hormesis

• Hormesis: Process by which low-to-moderate doses of a potentially harmful stress result in a beneficial adaptive response.
• Exercise-induced hormesis defines much of what we know about exercise-induced adaptation in the body.

Adaptation vs. Acclimatization

• Adaptation:
  • Change in structure or function of cell or organ system (i.e., hormesis).
  • Results in improved ability to maintain homeostasis.
• Acclimatization:
  • Adaptation to environmental stresses (hot, cold, or altitude environments).
• Altered gene expression is the molecular basis for physiological adaptation.
• The adaptation must reflect the stimulus.

The Central Dogma: DNA → RNA → Protein

Take Home Message

• Repeated bouts of exercise induce gradual changes in physiological function.
• Exercise challenges the homeostatic system.
• The stimulus/stress alters homeostasis.
• Hormesis: Exercise leads to adaptations, aka, new “set points” in homeostasis.
• The adaptation reflects the stimulus.
• Higher tolerance for perturbations during exercise.
• i.e., “The Training Effect”.

Energy: The Capacity to Perform Work

• Six forms of energy:
  • Chemical
  • Mechanical
  • Heat
  • Light
  • Electrical
  • Nuclear

Work in Biological Systems

Metabolism: Anabolism & Catabolism

• Metabolism: Sum of all chemical reactions that occur in the body.

How the Body Fuels Exercise

• Converts foods (macronutrients: carbohydrates/proteins/fats), with the help of oxygen, water, and/or specialized enzymes, into ATP (energy).
• ATP is catalyzed (broken down), releasing energy allowing work to be done (muscle contraction, building molecules the body needs, moving molecules around, heat production, etc.).

ATP: The Energy Currency of the Cell

• Powers all of the cell’s energy-requiring processes.
• Potential energy extracted from food (~50%).
• Energy is stored in high energy phosphate bonds of ATP and transferred to do work.
• ATP storage in muscle is low.

ATP Synthesis vs. ATP Hydrolysis

• ATP hydrolysis releases energy:
  • ATP + H2O \rightarrow ADP + Pi + Energy
• ATP synthesis requires energy:
  • Energy + ADP + P_i \rightarrow ATP
• ATP hydrolysis is catalyzed by ATPase.

Intermediary Molecules for Energy Transfer

• These molecules can be used in a controlled manner to provide free energy when required:
  • ATP
  • PCr
  • NAD
  • NADP
  • FAD
  • Coenzyme A

Bioenergetics Definition

• The transfer of energy in biological systems.
  • Energy is not created nor destroyed; instead, it is transferred from one form of energy to another.
  • Energy transfer is very inefficient; much of the energy during transfer is lost to heat (disorder).
  • Unlike mechanical systems, biological systems can’t utilize heat to produce work.
• Energy: The capacity to perform work.
• Work: Force production over a given distance.
• Power: Rate of work over time.

Energy Processes

• Energy-conserving process (endergonic): Stores or absorbs energy.
• Energy-releasing process (exergonic): Releases energy to surroundings.
• Coupled reactions: Exergonic drive endergonic.

Coupled Reaction

• Exergonic (gives off energy).
• Endergonic (absorbs energy).

Enzymes

• Enzymes facilitate energy conversion as biologic catalysts.
• Reduce required activation energy.
• Accelerate the rates of chemical reactions.
• Reaction rates depend upon: pH, temperature, and availability of substrates.
• Regulated steps in pathways.

Enzyme-Catalyzed Reactions

• Lock-and-key mechanism of enzyme action.
• Almost all enzymes' names end in –ase.
  • Kinases – add a phosphate group.
  • Dehydrogenases – Remove hydrogen atoms

3 Energy Systems

• Phosphagen System
  • Anaerobic
  • Immediate
• Glycolysis
  • Anaerobic
  • 5-10 seconds to activate
• Oxidative Phosphorylation/ Electron Transport Chain
  • Aerobic
  • 1-2 minutes to activate

Energy Systems for Muscular Work

Anaerobic ATP Production (two systems)

• ATP-PCr system
  • Immediate source of ATP.
    • ATP \xrightarrow{ATPase} ADP + P_i + energy
    • PCr \xrightarrow{creatine kinase} Pi + Cr + energy
  • Result: Energy released from breakdown of phosphocreatine is used to resynthesize ATP from ADP and Pi.
  • Occurs in the cytosol.
  • Lasts only ~10 sec.

Creatine Supplementation

• Depletion of PCr may limit short-term, high-intensity exercise.
• Creatine monohydrate supplementation:
  • Increased muscle PCr stores.
  • Some studies show improved performance in short-term, high-intensity exercise.
  • Increased strength and fat-free mass with resistance training.
• Glycolysis (anaerobic; 5-10 secs)
  • Substrates: Glucose and glycogen.
    • Muscle free glucose (low), blood glucose.
    • Glycogen stores in muscle.
  • Glycolysis occurs in the cytosol.
  • Synthesizes ATP and high-energy substrates via the breakdown of glucose to 2x pyruvate, then 2x lactate.
  • Energy Yield:
    • Glucose → → → 2 ATP + 2 Pyruvate

Conversion of Pyruvate to Lactate

• This reaction allows Glycolysis to continue functioning to synthesize ATP between 10 sec and 2 min of exercise, or until Aerobic metabolism can kick in.

Lactate Metabolism

• Lactate cannot be used in the active skeletal muscle.
• Sent to the blood:
  • Neighboring inactive muscle for use.
  • Liver.
• Lactic acid or lactate?

Aerobic Glycolysis

• Glycolysis
  • Glucose → 2x Pyruvate + 2x ATP + 2x NADH
• Pyruvate cannot be used in the exercising skeletal muscle during anaerobic metabolism.
  • Pyruvate → Lactate (anaerobic)
  • Pyruvate → Mitochondria (aerobic)

Importance of Glycolysis

• Very inefficient pathway (~30% of energy is conserved during glycolysis; remaining = heat).
• Short periods of energy needs.
  • 50m swim.
  • 100m running sprint.
  • Sprint at finish of 5k run.
• Lactate production.
  • Valuable “waste product”.
• Aerobic Glycolysis.
  • Most “bang” for your buck w/ CHO Glycolysis

Metabolic Fate of Pyruvate

• Pyruvate can be converted to Lactate in the cytosol under anaerobic conditions.
• Pyruvate can be transported to the Mitochondria under aerobic conditions.
• Pyruvate --(Anaerobic)--> Lactate (Cytosol)
• Pyruvate --(Aerobic)--> Acetyl CoA (Mitochondria)

Two Phases of Aerobic Glycolysis

Krebs Cycle

• Also known as the Tricarboxylic (TCA) Cycle or Citric Acid Cycle.
• 2nd phase of glucose metabolism.
• Pyruvate enters mitochondria.
• O_2 not actually utilized in Krebs cycle.
• The primary function of the Krebs cycle is to generate NADH and FADH2 (transport H^+ to ETC).
• Occurs in mitochondria.

Mitochondria: Cell’s “Powerhouse”

• Responsible for cellular respiration.
• Utilization of O_2 via oxidative metabolism to synthesize ATP.
• Contains the Krebs Cycle and electron transport chain (ETC).
• Large amounts of ATP can be synthesized via aerobic metabolism compared to anaerobic.
• ETC & ATP Synthase complexes.

Electron Transport Chain and Oxidative Phosphorylation

• Located in the inner mitochondrial membrane (between the intermembrane space and the mitochondrial matrix), the ETC is responsible for oxidative energy production.
• First pump = Complex I.
• Yellow hexagon = Complex II.
• Second pump = Complex III.
• Third pump = Complex IV.
• ATP Synthase = synthesizes ATP via aerobic metabolism.

Energy Yield from Glucose Metabolism

• Anaerobic Glycolysis: 2 ATP (0-2 ATP + 4 ATP = 2 ATP).
• Aerobic Glycolysis: 32 ATP (+2 ATP (from anaerobic) +30 ATP from Krebs & ETC) Total net yield of 32 ATP per glucose.

Glycogen Metabolism

• Glycogen: primary form of carbohydrate storage.
• Muscle & liver.
• Glucose polymers strung together in long branched chains.
• Glycogen synthesis.
• Enzyme: glycogen synthase.

Glycogenolysis

• Breakdown of glycogen to glucose: G-6-P.
• In muscle → glycolysis.
• In liver → blood.

Fat (Lipid) Metabolism

• Fat represents the body’s largest source of stored potential energy.
• Two storage depots: adipose tissue (subcutaneous & visceral) & intramuscular triglycerides.
• 3-C backbone + 3 fatty acids.
• “Lipolysis” – breakdown of lipids (fats).
• Utilization of lipids is oxidative: 1) mobilized, 2) activated (requires ATP), 3) transported into the mitochondria, and then 4) oxidized.
• Lipids are catabolized in a process called “β-oxidation”.
• β-oxidation produces Acetyl-CoA à Krebs Cycle.

Lipolysis: Cleavage of FFA

• Triacylglycerols: 3-C glycerol backbone with 3 fatty acids attached.
• “Free” fatty acids (FFA): long chain of carbons.
• 14-24 carbons in length.
• Hormone-sensitive Lipase catalyzes lipolysis.

Fuel Utilization for Exercise

• Contribution of Aerobic/Anaerobic ATP Production During Sporting Events

Energy System Contribution to Short-Duration Exercise

• Most activities <2 min in duration will be fueled predominantly by anaerobic metabolism.
• Duration & Intensity are the main determinants of metabolic fuel production.

Influence of Exercise Intensity on Muscle Fuel Source

Exercise Intensity and Fuel Utilization

• Low-intensity exercise (<35% VO_2 max)
  • Lipids are primary fuel
• Moderate to High-intensity exercise (>50% VO_2 max)
  • Carbohydrates are primary fuel

Low-Intensity Exercise for Burning Fat

• At low exercise intensities (~20% VO_2 max):
  • High percentage of energy expenditure (~60%) derived from fat.
  • However, total energy expended (kcal burned) is low (~2.5 kcal/min energy expenditure).
  • Total fat oxidation is also low (~1.5 kcal/min from fat).
• At higher exercise intensities (~50% VO_2 max):
  • Lower percentage of energy (~40%) from fat.
  • Total energy expended is higher (5-10 kcal/min energy expenditure).
  • Total fat oxidation is also higher (2-4 kcal/min from fat).

Lactate Threshold

• The point at which blood lactate rises systematically during incremental exercise.
• Appears at ~50–60% VO2 max in untrained subjects and at higher work rates (65–80% VO2 max) in trained subjects.
• Also called:
  • Anaerobic threshold.
  • Onset of blood lactate accumulation (OBLA) - Blood lactate levels reach 4 mmol/L.
• Training Increases Lactate Threshold.

Lactate Threshold Uses

• Prediction of performance (combined with VO_2 max).
• Planning training programs (marker of training intensity; choose a training HR based on LT).
• Lactate does NOT cause post-exercise muscle soreness.

Oxygen Consumption

• Volume of oxygen consumed (utilized) for energy production using aerobic/oxidative metabolism.
• VO_2 increases proportionately with exercise intensity.
• Expressed two ways:
  • Absolute – (L/min)
  • Relative – (mL/kg/min) normalized to body mass.

Energy Requirements at Rest

• Almost 100% of ATP produced by aerobic metabolism.
• Predominant fuel source is fat (~70%).
• Blood lactate levels are low (<1.0 mmol/L).
• Resting O_2 consumption:
  • ~0.25 L/min (absolute).
  • ~3.5 mL/kg/min (relative).

Maximal Oxygen Consumption

• is the maximal amount of oxygen that can be consumed by a person
• VO_2max provides a quantitative measure of a person’s ability to resynthesize ATP using aerobic metabolism
• Average values for college-aged
  • Untrained:
    • Men 35-45 mL/kg/min
    • Women 30-40 mL/kg/min
  • Trained:
    • Men 50-60 mL/kg/min
    • Women 45-55 mL/kg/min

Metabolic Responses to Incremental Exercise

• Oxygen consumption increases proportionately with increases in work rate until VO_2 max is reached.
• max:
  • No further increase in VO_2 with increasing work rate.
  • “Physiological ceiling” for delivery & uptake of O_2 to muscle.

Summary: Oxygen Consumption

• VO2 @ rest = ~ 3.5 mL/kg/min
  • Low energy expenditure
  • Predominantly aerobic metabolism
  • Lipids as fuel (60-70%)
• VO2 @ max exercise
  • High energy expenditure
  • Maximal aerobic metabolism
  • CHO as fuel (~100%)
• max values
  • Untrained:
    • Men 35-45 mL/kg/min
    • Women 30-40 mL/kg/min
  • Trained:
    • Men 50-60 mL/kg/min
    • Women 45-55 mL/kg/min

Factors Affecting VO_2max

• Mode of activity.
• Heredity.
• State of training.
  • Maximum ability of the cardiorespiratory system to deliver oxygen to the muscle.
  • Ability of muscles to use oxygen and produce ATP aerobically.
• Sex.
• Body size and body composition.
• Age.

Rest-to-Exercise Transitions

• ATP utilization & production increase immediately.
• Oxygen consumption increases rapidly, reaching steady state within 1–4 minutes.
• After steady state is reached, ATP requirement is met through aerobic ATP production.
• Initial ATP production through anaerobic pathways:
  • Phosphagen system
  • Glycolysis
• Oxygen deficit: Lag in oxygen uptake at the beginning of exercise.

Oxygen Debt

• Also known as Excess Post-exercise Oxygen Consumption (EPOC)
• “Rapid” portion of O_2 debt:
  • Resynthesis of stored PC.
  • Replenishing muscle and blood O_2 stores.
• “Slow” portion of O_2 debt:
  • Elevated heart rate and breathing = increased energy need.
  • Elevated body temperature = increased metabolic rate.
  • Elevated epinephrine and norepinephrine = increased metabolic rate.
  • Conversion of lactate to glucose (gluconeogenesis).