9/25 MOD 2: Energy Systems in Exercise — Comprehensive Notes

Energy systems overview
- Three systems contribute to ATP production during exercise: phosphocreatine (ATP-PCr) system, anaerobic glycolysis, and aerobic (mitochondrial) metabolism.
- All three can be active at once; some respond more quickly and dominate at different times depending on intensity.
- Key timeframes often cited:
- Phosphocreatine (PCr) system: rapid ATP resynthesis for very short, high-intensity efforts; typically ~5–10 seconds of all-out work.
- Anaerobic glycolysis: fast but limited by lactate/acid buildup; effective for ~3–4 minutes of high-intensity effort before fatigue limits it.
- Aerobic system: slower to ramp up, but supports sustained activity over minutes to hours; the primary energy source for longer-duration exercise.
- Example of energy contribution by duration (approximate):
- 400 m sprint: ~30% aerobic, ~70% anaerobic
- 800 m: roughly 50/50
- 10,000 m: mostly aerobic
Phosphocreatine (ATP-PCr) system
- Stores a tiny amount of high-energy phosphate (phosphocreatine) in muscle.
- Donates phosphate to ADP to rapidly regenerate ATP during short, intense bursts: ADP + \,\text{PCr} \rightarrow ATP + \mathrm{Cr}
- This system is non-sustained; once PCr is depleted, energy must come from other sources.
- Repletion happens during recovery, primarily via aerobic metabolism (hours to minutes depending on intensity).
- Key takeaway: PCr provides immediate ATP but is exhausted quickly; it is replenished more slowly than it is used.
Anaerobic glycolysis (glycolytic system)
- Starts in parallel with PCr; uses glucose to produce ATP in the cytosol without requiring oxygen.
- Glucose entry and phosphorylation steps involve enzymes, notably:
- Hexokinase: \text{Glucose} + \text{ATP} \rightarrow \text{Glucose-6-phosphate} + \text{ADP}
  - Facilitates glucose trapping inside the cell.
- Phosphofructokinase (PFK): a rate-limiting, highly regulated enzyme sensitive to hydrogen ion concentration (acid): \text{Fructose-6-phosphate} + \text{ATP} \rightarrow \text{Fructose-1,6-bisphosphate} + \text{ADP}
  - PFK is the “thermostat” that slows glycolysis when acidity rises (lower pH).
- Net glycolytic ATP yield: \text{Glucose} \rightarrow 2\ \text{pyruvate (or lactate under anaerobic conditions)} with gross ATP yield of 4 ATP per glucose and a net yield of 2 ATP per glucose (4 produced, 2 consumed).
- End product under anaerobic conditions: pyruvate is reduced to lactate, regenerating NAD+ for glycolysis.
- Lactate fate (interconnected pathways):
- In fast-twitch fibers, lactate can be produced and accumulate; some lactate is taken up by slow-twitch fibers and oxidized (lactate as fuel).
- Cori cycle: liver can convert lactate back to pyruvate and then to glucose (gluconeogenesis) for reuse by tissues; this process is limited by hepatic blood flow during heavy exercise.
- Lactate and acid-base balance:
- Lactate exists with a hydrogen ion; the acidic component is what lowers pH and contributes to fatigue.
- Lactic acid splits into lactate (ion) and H⁺; the hydrogen ions contribute to acidosis and inhibit enzymes like PFK.
Lactic acid, buffering, and ventilation
- Hydrogen ions (acid) are problematic for enzyme function and nerve/muscle contraction; buffering is essential.
- In the bloodstream, bicarbonate (HCO₃⁻) buffers excess H⁺: \mathrm{HCO}3^- + \mathrm{H}^+ \rightarrow \mathrm{H}2\mathrm{CO}3 \rightarrow \mathrm{CO}2 + \mathrm{H}_2O}
- CO₂ is the primary driver for increasing ventilation (breathing rate) during intensified exercise; CO₂ buildup stimulates breathing more than O₂ availability.
- An illustrative aside from respiration: holding breath demonstrations show how deep breathing to “blow off CO₂” can delay the urge to breathe briefly; in real exercise, CO₂ drives ventilation, which helps clear H⁺ via buffering and exchange with the lungs.
- Recovery breathing: through a light cooldown and continued breathing, lactate clearance can occur; lactate is largely cleared within about five minutes after exercise, and lactic acid is not a lingering factor beyond that timeframe in healthy individuals.
Fate of lactate and liver metabolism (Cori cycle)
- Slow-twitch (type I) fibers can oxidize lactate to pyruvate and feed it into mitochondria for ATP production; lactate can also be converted to glucose in the liver via gluconeogenesis (Cori cycle).
- The Cori cycle is most effective at rest or during lower-intensity recovery when blood flow to the liver is adequate.
- During heavy exercise, hepatic blood flow is reduced; the liver cannot rapidly convert lactate to glucose in real-time to rescue exercise performance.
The aerobic system (mitochondrial energy production)
- Conceptual model: mitochondria are like batteries that gather hydrogen (from food substrates) and convert it into a flow of electrons to drive ATP production.
- Inner mitochondrial membrane hosts the electron transport system (ETS/ETC) where protons are pumped to create a proton-motive force used by ATP synthase to produce ATP.
- Substrates feeding the mitochondria:
- Carbohydrates: glucose is converted to acetyl-CoA via glycolysis and pyruvate dehydrogenase; oxaloacetate (OAA) is required to combine with acetyl-CoA in the citric acid (Krebs) cycle. The cycle oxidizes acetyl-CoA to CO₂, generating NADH and FADH₂ for the ETC.
- Fats: fatty acids are broken down via beta-oxidation to acetyl-CoA before entering the Krebs cycle.
- Cofactors involved in shuttling hydrogens: nicotinamide adenine dinucleotide (NAD⁺/NADH) and riboflavin-derived flavin adenine dinucleotide (FAD/FADH₂) act as hydrogen carriers; they are sometimes referred to as energy vitamins (e.g., B vitamins) that assist in transporting hydrogens to the ETC.
- Key entry point: acetyl-CoA is the entry point for both carbohydrate- and fat-derived substrates into the Krebs cycle.
- Important caveat: oxaloacetate supply from carbohydrate metabolism is necessary to sustain the cycle; carbohydrate deficiency can limit this cycle and promote ketone body formation (ketosis).
- Overall: aerobic metabolism is slower to ramp up but provides the most substantial, sustainable ATP production when oxygen is available.
- Practical note: Fat oxidation requires ongoing aerobic activity and is favored at moderate, prolonged intensities; maximal fat loss occurs with extended aerobic work rather than brief, intense efforts that rely on anaerobic glycolysis.
Fat metabolism and lipolysis (breaking down fat stores)
- Triglycerides in adipose tissue are the main fat storage form (glycerol backbone + three fatty acids).
- Step 1: mobilization
- A hormone signal activates hormone-sensitive lipase (HSL) to hydrolyze triglycerides into glycerol and free fatty acids (FFAs).
- Enzymes/hormones involved in mobilization include epinephrine (adrenaline), norepinephrine, cortisol, growth hormone, and others; ephedra historically used as a stimulant to increase lipolysis but carries serious risks.
- The hormone signals (epinephrine, norepinephrine, cortisol, growth hormone) activate HSL, initiating fat mobilization.
- The glycerol portion dissolves in blood and can enter glycolysis; the FFAs must be transported in the blood by albumin (and also by lipoproteins for some contexts).
- Step 2: transport
- FFAs circulate bound to albumin due to their hydrophobic nature; they cannot freely travel in plasma.
- Some FFAs circulate bound to lipoproteins (e.g., chylomicrons, VLDL); dietary and metabolic factors influence transport.
- Step 3: uptake into muscle mitochondria
- FFAs bind to receptors or transporters on muscle cell membranes and are transported inside the cell.
- Inside the cell, FFAs undergo activation and import into mitochondria for beta-oxidation to acetyl-CoA, feeding the Krebs cycle.
- Step 4: beta-oxidation and entry to Krebs cycle
- Beta-oxidation cleaves FFAs into two-carbon acetyl-CoA units, which enter the Krebs cycle and are oxidized for energy.
- The hydrogen atoms (carried by NADH and FADH₂ in the oxidation steps) are shuttled to the ETC to produce ATP.
- Step 5: transport and storage considerations
- Fats require a transport mechanism (albumin for FFAs; lipoproteins for some forms) to reach tissues that will oxidize them.
- Receptors for fatty acids on cell membranes can increase with training, improving fat uptake and oxidation capability; endurance training increases the density of these receptors and enhances fat burning.
- Practical consequences for fat loss:
- Exercise increases epinephrine levels, which activates HSL and mobilizes fat.
- Training enhances fat oxidation capacity by increasing receptor availability and improving fat transport to mitochondria.
- Diet can influence fat storage via insulin; high insulin promotes triglyceride storage, whereas low insulin (e.g., via physical activity and appropriate carbohydrate management) supports fat mobilization.
- Fat storage depots:
- Subcutaneous fat (under the skin)
- Intramuscular fat (between muscle fibers)
- Visceral fat (around organs) – associated with higher health risk; visceral fat is particularly concerning with aging.
- A vivid example of fat mobilization and activation:
- A modern anecdote highlights that a single bout of walking can mobilize fat and increase fatty acid receptor density, enhancing fat utilization later. Endurance activity improves fat utilization compared with short, intense efforts.
Practical considerations for fat loss and exercise strategy
- To maximize fat loss, emphasize aerobic, prolonged, moderate-intensity exercise rather than brief, high-intensity efforts for fat burning, though the latter can be valuable for overall fitness and energy expenditure.
- Energy balance concept: burning fat requires movement that creates an energy demand; simply taking diet pills or stimulants without physical activity does not effectively mobilize or oxidize fat.
- Typical caloric value: approximately 1\ ext{lb of fat} \approx 3500\ \text{kcal}; thus, gradual fat loss during a sustainable program is safer and more realistic than rapid, large losses.
- The combination of dietary management (reducing unnecessary fat intake and managing carbohydrates) and regular movement is essential for sustainable fat loss.
- Ketosis and carbohydrate intake:
- Glucose is essential for efficient fat metabolism because certain intermediates (e.g., oxaloacetate) derived from carbohydrate metabolism support the Krebs cycle.
- In carbohydrate-restricted states, ketone bodies may become a more prominent fuel source, but fat oxidation still depends on an intact aerobic pathway.
Key takeaways and mental models
- Think of energy metabolism as a layered battery system:
- Immediate, rapid ATP from PCr (fastest system)
- Fast but limited ATP from anaerobic glycolysis (glucose -> lactate pathway)
- Slow, sustained ATP from aerobic metabolism (mitochondria) using carbohydrates and fats
- Lactic acid is not simply “the problem” but a signal and fuel shuttling between tissues; lactate can be reused as fuel and converted back to glucose in the liver (Cori cycle), but this is limited by blood flow and recovery time.
- Oxygen plays a central buffering role by accepting electrons in the mitochondria; lack of oxygen leads to lactate accumulation and acidosis, while adequate oxygen enables continued aerobic ATP production.
- Training status affects fat oxidation: more fat oxidation capacity is associated with more fatty acid transporters, better transport of fatty acids into mitochondria, and greater reliance on fat as a fuel during sustained activity.
- Everyday relevance: fat loss is best achieved through long-duration, moderate-intensity activity, not only high-intensity workouts; a sustainable routine (e.g., walking, cardio, or other enjoyable activities) improves overall energy expenditure and fat utilization over time.
Quick glossary and formulas
- PCr: phosphocreatine; ATP-PCr system provides immediate ATP.
- Glycolysis steps (highlights):
- Hexokinase: \text{Glucose} + \text{ATP} \rightarrow \text{Glucose-6-phosphate} + \text{ADP}
- Phosphofructokinase (PFK): \text{Fructose-6-phosphate} + \text{ATP} \rightarrow \text{Fructose-1,6-bisphosphate} + \text{ADP}
- Lactate/pH: \text{pyruvate} + \text{NADH} + H^+ \rightarrow \text{lactate} + \text{NAD}^+
- Lactate buffering and exhalation: \mathrm{HCO}3^- + \mathrm{H}^+ \rightarrow \mathrm{H}2\mathrm{CO}3 \rightarrow \mathrm{CO}2 + \mathrm{H}_2\mathrm{O}
- Glucose to ATP in aerobic respiration: acetyl-CoA enters the Krebs cycle; NADH/FADH₂ feed the ETC; O₂ is the terminal electron acceptor, forming water.
- Fat energy: triglyceride breakdown yields glycerol + FFAs; FFAs undergo beta-oxidation to acetyl-CoA; acetyl-CoA enters the Krebs cycle; overall fat oxidation provides substantial ATP but requires adequate oxygen and a sustained aerobic pace.
- Fat loss energy cost: 1\ \text{lb fat} \approx 3500\ \text{kcal}
- Physiology note: liver blood flow is reduced during heavy exercise, limiting Cori cycle capacity in real-time; recovery relies more on slow-twitch fibers and aerobic clearance.
Ethical and practical considerations mentioned
- Historical diet pills (ephedra) were linked to dangerous cardiovascular events due to stimulant effects (epinephrine-like activity).
- Caffeine is a common stimulant that can raise catecholamine levels and influence lipolysis; safety and context matter.
- Emphasis on evidence-based strategies: sustainable activity, balanced diet, and avoidance of unsafe stimulants for weight/fat loss.
Summary connections to broader physiology
- The three energy systems are interdependent and dynamically regulated by substrate availability (glucose, fat), oxygen supply, and hormonal signals.
- Training adapts the body to become more efficient at fat oxidation by increasing fatty acid transporters and improving mitochondrial function.
- Understanding these pathways helps explain why different athletes excel in different events and why fat loss requires a long-term, balanced approach rather than quick fixes.

There are three main energy systems that produce ATP during exercise, all active at once but dominating at different intensities and durations:

Phosphocreatine (ATP-PCr) system

Provides rapid ATP for very short, high-intensity efforts (up to
~10 seconds).
Uses stored phosphocreatine (PCr) to regenerate ATP: ADP + ext{PCr}
ightarrow ATP + Cr
Depletes quickly and is replenished during recovery via aerobic metabolism.

Anaerobic glycolysis (glycolytic system)

Uses glucose to produce ATP without oxygen, effective for high-intensity efforts lasting
~3–4 minutes before fatigue from lactate/acid buildup.
Key enzymes:
- Hexokinase: Traps glucose in cell: ext{Glucose} + ext{ATP}
  ightarrow ext{Glucose-6-phosphate} + ext{ADP}
- Phosphofructokinase (PFK): Rate-limiting, sensitive to acidity (low pH):
  ext{Fructose-6-phosphate} + ext{ATP}
  ightarrow ext{Fructose-1,6-bisphosphate} + ext{ADP}
Net yield: 2 ATP per glucose. Pyruvate is reduced to lactate, regenerating NAD+ for continued glycolysis.
Lactate exists with a hydrogen ion (H⁺), which causes acidosis, inhibiting enzymes and contributing to fatigue.
Lactate can be used as fuel by slow-twitch fibers or converted to glucose in the liver via the Cori cycle, which is limited during heavy exercise due to reduced hepatic blood flow.

Aerobic system (mitochondrial energy production)

Slower to activate but provides substantial, sustained ATP over minutes to hours, using oxygen.
Mitochondria oxidize carbohydrates (glucose via acetyl-CoA) and fats (fatty acids via beta-oxidation to acetyl-CoA) in the Krebs cycle, producing NADH and FADH₂.
These cofactors shuttle hydrogen to the electron transport system (ETS) on the inner mitochondrial membrane, driving ATP production via ATP synthase.
Acetyl-CoA is the common entry point for carbohydrate and fat metabolism into the Krebs cycle.
Oxaloacetate from carbohydrate metabolism is crucial to sustain the cycle; carbohydrate deficiency can limit it.
Fat oxidation is primarily favored at moderate, prolonged intensities; endurance training enhances fat oxidation capacity by increasing fatty acid transporters and improving mitochondrial function.

Lactic acid, buffering, and ventilation

Hydrogen ions from lactate lower pH, impairing enzyme function and muscle contraction.
Bicarbonate (HCO₃⁻) buffers H⁺, forming CO₂ ( ext{HCO}3^- + ext{H}^+ ightarrow ext{H}2 ext{CO}3 ightarrow ext{CO}2 + ext{H}_2 ext{O}), which drives increased ventilation.
Lactate is typically cleared within ~5 minutes post-exercise with proper recovery.

### Practical considerations for fat loss
- Maximizing fat loss requires prolonged, moderate-intensity aerobic exercise combined with dietary management.
- Fat mobilization depends on hormones (e.g., epinephrine activating hormone-sensitive lipase for triglyceride breakdown into glycerol and FFAs).
- Fat requires transport (FFAs by albumin) and uptake into muscle mitochondria for beta-oxidation.
- Fat loss is gradual (1 ext{ lb fat} hickapprox 3500 ext{ kcal}) and requires a sustainable approach; diet pills or stimulants alone are ineffective and potentially dangerous.

Three energy systems produce ATP during exercise, operating concurrently but dominating at different intensities and durations:

Phosphocreatine (ATP-PCr) system: Supplies rapid ATP for very short, high-intensity efforts ($\sim5-10$ seconds) by regenerating ATP from stored phosphocreatine (ADP + \text{PCr} \rightarrow ATP + \mathrm{Cr}). It depletes quickly and replenishes during recovery.
Anaerobic glycolysis: Uses glucose to produce 2 net ATP per glucose in the cytosol without oxygen, sustaining high-intensity efforts for $\sim3-4$ minutes. Key enzymes include hexokinase (trapping glucose) and phosphofructokinase (PFK), which is rate-limiting and sensitive to hydrogen ion (H⁺) concentration. Pyruvate is converted to lactate, regenerating NAD+ for continued glycolysis. The H⁺ from lactic acid lowers pH, inhibiting enzymes and contributing to fatigue. Lactate can be used as fuel by slow-twitch fibers or converted to glucose in the liver (Cori cycle), though liver conversion is limited during heavy exercise.
Aerobic system: Offers substantial, sustained ATP over minutes to hours, requiring oxygen. Mitochondria oxidize carbohydrates and fats (both converting to acetyl-CoA) in the Krebs cycle. NADH and FADH₂ shuttle hydrogen atoms to the electron transport system (ETS), where ATP is produced. Acetyl-CoA is the entry point, and oxaloacetate (derived from carbohydrates) is essential to sustain the cycle. This system is primary for moderate, prolonged activity; training enhances fat oxidation by improving mitochondrial function and fatty acid transport.
Lactic acid, buffering, and ventilation: High H⁺ levels impair enzyme function and muscle contraction. Bicarbonate buffers H⁺ (\mathrm{HCO}3^- + \mathrm{H}^+ \rightarrow \mathrm{H}2\mathrm{CO}3 \rightarrow \mathrm{CO}2 + \mathrm{H}_2\mathrm{O}), producing CO₂, which stimulates increased breathing. Lactate is typically cleared within $\sim5$ minutes post-exercise.
Practical considerations for fat loss: Maximizing fat loss requires prolonged, moderate-intensity aerobic exercise combined with dietary management. Hormones (e.g., epinephrine activating hormone-sensitive lipase) mobilize fat from triglycerides into glycerol and free fatty acids (FFAs). FFAs are transported by albumin and undergo beta-oxidation in mitochondria for energy. Fat loss is a gradual process (1\ \text{lb fat} \approx 3500\ \text{kcal}) and depends on sustainable activity rather than quick fixes or unsafe stimulants.