Chapter 11 – Exercise Physiology
Exercise physiology is the study of how the human body responds and adapts to physical activity. The body’s response to exercise is the only objective measure for evaluating its capacity to handle physical stress. In other words, exercise physiology examines the body in motion.
All the effects of systematic athletic activity are the result of both the initial stimulus and the body’s adaptive response to it. The ultimate goal of these adaptations is the optimization of performance. Regular training can alter metabolism so profoundly that the metabolic profile of a trained individual differs not only during exercise but also at rest, compared with that of an untrained person.
Exercise induces metabolic changes not only in the active muscles but also in other organs and tissues, such as the liver and adipose tissue. Importantly, metabolism does not immediately return to baseline after exercise. Many changes persist for hours or even days, while others appear only during recovery rather than during the activity itself.
The physiological effects of exercise can be categorized into two types:
- Acute effects – responses triggered by a single bout of exercise.
- Chronic effects – adaptations resulting from regular, repeated training sessions over time.
Determinants of Energy Source Selection During Exercise
The body’s choice of fuel during exercise depends on several factors:
- Exercise intensity – higher intensities shift energy production toward carbohydrates.
- Exercise duration – prolonged activity increases reliance on fat metabolism.
- Type of training program – whether continuous, interval, or variable intensity.
- Environmental conditions – such as ambient temperature and humidity.
- Sex – hormonal differences influence substrate utilization.
- Age – metabolic efficiency and recovery capacity vary across the lifespan.
- Training status – trained individuals exhibit enhanced efficiency and greater metabolic flexibility.
- Diet – nutritional habits directly affect energy availability and utilization.
- Genetics – inherited factors can predispose individuals to specific metabolic and performance profiles.
This framework provides the foundation for understanding how physical activity shapes human performance, health, and long-term adaptation.
Exercise Types by Energy System
Human movement relies on energy production, which can occur either in the presence of oxygen (aerobic metabolism) or without it (anaerobic metabolism). Exercise is therefore classified according to the predominant energy system used:
Aerobic Exercise
- Primary energy source: the aerobic metabolic pathway.
- Characteristics:
- Involves large or multiple muscle groups, often working continuously or in combination.
- Increases oxygen uptake and heart rate.
- Duration is typically more than 30 minutes.
- Frequency ranges from 3–5 sessions per week. Endurance athletes may train more frequently, but this carries an increased risk of injury (Pollock et al., MSSE 1998).
- Intensity:
- At least 55–65% of maximum heart rate for general health benefits.
- 70–90% of maximum heart rate for performance improvement.
- Well-trained athletes may operate at even higher intensities.
- Indicators:
- Activities lasting 15–20 minutes or more,
- Heart rates exceeding 120 beats per minute.
- Examples of aerobic activities: walking, jogging, long-distance running, swimming, cycling, dancing, rowing, mountain skiing, and similar endurance sports.
Anaerobic Exercise
- Primary energy source: the anaerobic metabolic pathway.
- Definition: Physical activity during which the demand for oxygen exceeds its supply. As a result, the cardiovascular system cannot deliver sufficient oxygen to the working muscles.
- Process:
- Muscles must rely on alternative energy sources, such as stored ATP and glycogen, leading to the production of lactate.
- This energy system supports short-duration, high-intensity efforts but fatigues quickly.
- Examples: sprinting, high-intensity interval training (HIIT), heavy resistance training, jumping, and explosive movements.
Combined Contribution
In reality, both systems contribute simultaneously to energy production, with one predominating depending on the intensity and duration of exercise.
- Maximal performance can be described as:
Maximum Output = Maximum Aerobic Power + Maximum Anaerobic Power
Physiological Limitations of Aerobic Energy
Aerobic energy production is limited by the body’s ability to transport and deliver oxygen to the working muscles. As exercise intensity increases, oxygen consumption (VO₂) also rises to meet the demand for ATP production.
With improved physical conditioning:
- The cardiovascular system becomes more efficient at delivering oxygen.
- The musculoskeletal system becomes more effective at utilizing oxygen.
- The overall VO₂max (maximum oxygen uptake per minute) increases, enabling higher performance.
Determinants of Athletic Performance
High-level performance depends on multiple physiological and anatomical factors, including:
- Aerobic capacity
- Anaerobic capacity
- Type and distribution of muscle fibers
- Body morphology and somatotype
- Anthropometric characteristics
- Physical abilities (strength, speed, flexibility, endurance)
Anthropometric characteristics include measurements such as: height, weight, circumferences, bone lengths (e.g., humerus or femur), skinfold thickness, basal metabolic rate (BMR), and body composition. These factors are influenced by sex, age, ethnicity, and genetic background (Baechle, 1994).
Aerobic Capacity
Aerobic capacity reflects cardiorespiratory endurance. It is defined as the ability to perform long-duration, submaximal exercise under a sufficient balance between oxygen uptake and consumption.
The maximum rate at which muscles can consume oxygen per unit of time is called maximal oxygen uptake (VO₂max), expressed in milliliters of oxygen per kilogram of body weight per minute (ml/kg/min). VO₂max is the gold-standard measure of aerobic capacity and one of the most important indicators of physical fitness.
Categories of Aerobic Capacity
- Maximal aerobic capacity: Reflects the limits of oxygen transport and utilization. Equivalent to VO₂max.
- High aerobic capacity: Represents the maximum oxygen consumption by working muscles without activating anaerobic metabolism. Corresponds to the anaerobic threshold.
- Low aerobic capacity: Refers to oxygen use during light effort, sufficient to trigger functional adaptations. Corresponds to the aerobic threshold.
Determinants and Significance
- VO₂max depends on age, sex, training status, muscle mass, health, and medications.
- It increases until about age 20, then decreases by ~10% per decade.
- Women generally show 10–20% lower VO₂max values than men due to lower muscle mass, hemoglobin levels, and stroke volume.
- Athletes consistently demonstrate much higher VO₂max compared to untrained individuals of the same age and sex.
- Low VO₂max is linked with poor health and potential underlying pathology.
The Fick Equation
Aerobic performance is explained by the Fick principle, which defines VO₂max as:
VO₂max = Cardiac Output (HR × SV) × Arteriovenous O₂ Difference (A–V O₂ diff)
Where:
- Cardiac Output (CO) = Heart Rate (HR) × Stroke Volume (SV)
- Stroke Volume (SV) = the amount of blood pumped per beat (end-diastolic volume – end-systolic volume)
- Arteriovenous O₂ Difference = the difference in oxygen content between arterial and venous blood
This equation links cardiovascular function (delivery of oxygen) with muscular function (utilization of oxygen).
Thresholds
- Aerobic threshold: The exercise intensity at which blood lactate concentration first rises above resting levels (~2.5 mmol/L).
- Anaerobic threshold: The intensity at which lactate production exceeds clearance (~4 mmol/L), signaling a shift toward anaerobic glycolysis. This is a critical predictor of endurance performance.
- Lactate threshold: Anaerobic threshold measured via blood lactate levels.
- Ventilatory threshold: Anaerobic threshold determined by gas exchange, observed when ventilation increases disproportionately to VO₂.
- Respiratory Quotient (RQ) and Respiratory Exchange Ratio (RER) describe the ratio of carbon dioxide produced to oxygen consumed (RER = VCO₂ / VO₂).
- Indicates which substrates (carbohydrates vs. fats) are predominantly used for energy.
A higher anaerobic threshold means delayed lactate accumulation, allowing athletes to sustain higher intensities for longer. Typically, this occurs at 83–87% of maximal heart rate, with elite athletes reaching even higher values.
Anaerobic Capacity
Anaerobic capacity is defined as the ability to perform short-duration, maximal-intensity work under conditions of limited oxygen availability.
Subcategories
- Anaerobic muscular power: The peak force output achieved in a very short duration (5–10 seconds). This corresponds to the alactic anaerobic phase (ATP–PCr system).
- Anaerobic muscular endurance: The mean power output sustained during 30–45 seconds of maximal effort, reflecting the lactic anaerobic phase (glycolytic system).
- Assessed by average work produced, post-exercise blood lactate, and power decline (% fatigue index).
Lactic Acid
Lactic acid is one of the most frequently measured biochemical markers in sports science. During exercise, lactic acid is produced in the muscles through anaerobic glycolysis, where glucose and glycogen are converted into pyruvate and, in the absence of sufficient oxygen, into lactate. From there, lactate diffuses through the cell membrane into the bloodstream.
It serves as an important indicator of both anaerobic and aerobic capacity, since its production depends on exercise type, intensity, duration, fitness level, and age. When exercise intensity exceeds the anaerobic threshold, lactate begins to accumulate in the blood. If exercise continues, the associated drop in pH (acidosis) contributes to fatigue.
Contrary to older beliefs, lactate itself is not the direct cause of performance decline (Brooks, 1985; Gladden, 2004). Instead, it is the associated increase in hydrogen ion (H⁺) concentration that lowers pH, producing pain and reducing muscular efficiency.
Lactate Removal and Recovery
The concentration of lactic acid in the blood peaks a few minutes after exercise and is influenced by:
- the rate of production in muscle cells,
- diffusion into the blood,
- clearance from circulation, and
- buffering by blood systems.
A key strategy to accelerate lactate clearance is active recovery (light exercise at 30–45% of VO₂max). Active recovery enhances blood flow and circulation, facilitating lactate removal more effectively than passive rest. However, it delays glycogen resynthesis (Choi et al., 1994).
Metabolic Acidosis
Metabolic acidosis refers to any process that lowers body pH due to acid accumulation or loss of buffering bicarbonates. During exercise, the breakdown of ATP into ADP and inorganic phosphate releases hydrogen ions (H⁺).
An increase in H⁺ concentration is the true cause of acidosis during high-intensity exercise, as it lowers pH below 7. This disrupts enzymatic activity, impairs muscle contraction, and ultimately contributes to fatigue.
Fundamental Energy Systems
Human performance relies on the body’s ability to produce and manage energy. This energy is supplied through two primary metabolic pathways: anaerobic metabolism and aerobic metabolism. Each pathway has its own substrates, speed of energy production, and byproducts, making them more suitable for specific types of activity.
Anaerobic Metabolism
In anaerobic metabolism, energy is produced without oxygen, primarily through the breakdown of ATP, phosphocreatine (PCr), and carbohydrates (glucose). This pathway is critical during short-duration, high-intensity activities, such as sprints and weightlifting.
- Byproducts: energy (ATP), water (reused), carbon dioxide (exhaled), and lactic acid, which lowers pH.
- Advantages: rapid ATP production, enabling immediate muscular power.
- Disadvantages: accumulation of hydrogen ions from lactic acid, leading to decreased pH, enzyme inhibition, and reduced performance.
Aerobic Metabolism
Aerobic metabolism requires oxygen and occurs primarily in the mitochondria, often referred to as the “aerobic powerhouses” of the cell. It uses carbohydrates, fats, and proteins as fuel sources and is the dominant system at rest and during prolonged, lower-intensity activity.
- Byproducts: energy (ATP), water (reused), and carbon dioxide (exhaled).
- Advantages: efficient and sustainable energy production for long-duration exercise.
- Disadvantages: slower rate of ATP production compared to anaerobic pathways.
Energy Systems (ATP Resynthesis)
Energy for muscular contraction is regenerated through three main systems, each with distinct roles depending on the activity:
- ATP-CP System (Phosphagen System)
- Also known as the anaerobic alactic system, it provides immediate energy from stored ATP and creatine phosphate (PCr).
- Does not require oxygen and does not produce lactic acid.
- Dominant during the first 3–10 seconds of intense muscular activity (e.g., 100 m sprint, explosive lifts).
- Limited by the small storage capacity of ATP and PCr in muscle cells.
- Anaerobic Glycolysis (Lactic System)
- Provides short-term energy (up to ~45 seconds) by partially breaking down glucose without oxygen, producing pyruvate and lactic acid.
- Key enzyme: phosphofructokinase (PFK), which regulates glycolysis rate.
- Produces moderate amounts of ATP, useful for activities like 400 m sprinting or high-intensity intervals.
- Lactic acid acts as both a performance limiter (via acidosis) and an energy reservoir (recycled through the Cori Cycle).
- Aerobic (Oxidative) System
- The most complex and sustainable energy pathway.
- Fuels long-duration, lower-intensity activities using carbohydrates (glucose/glycogen), fats (fatty acids), and proteins (amino acids).
- Consists of three main stages:
- Aerobic Glycolysis – pyruvate is converted to acetyl-CoA in the presence of oxygen.
- Krebs Cycle (Citric Acid Cycle) – acetyl-CoA is fully oxidized to hydrogen and carbon dioxide.
- Electron Transport Chain (Oxidative Phosphorylation) – hydrogen atoms are split into protons and electrons; electrons pass along enzyme complexes, generating large amounts of ATP, while protons combine with oxygen to form water.
- Capable of producing vast amounts of ATP, but with a slower response time compared to anaerobic systems.
📊 Quick Comparison of Energy Systems
Energy System | Oxygen Use | Duration Dominance | ATP Yield | Byproducts | Example Activity |
---|---|---|---|---|---|
ATP-CP System | No | 0–10 seconds | Very low | None | 100 m sprint, jump |
Anaerobic Glycolysis | No | 10–45 seconds | Moderate | Lactic acid | 400 m run, HIIT |
Aerobic System | Yes | >2 minutes | Very high | CO₂, H₂O | Marathon, cycling |
Energy Sources During Exercise
The predominant energy system used during exercise depends on the intensity and duration of the effort. Different pathways dominate depending on whether the activity is short, intense, or prolonged.
Energy Contribution by Effort Duration
- Supramaximal efforts up to 10 seconds:
Energy is supplied almost exclusively from the breakdown of phosphocreatine (PCr). Anaerobic glycolysis cannot respond rapidly enough within this timeframe. - Maximal efforts of 30 seconds to 2 minutes:
The majority of energy is produced by anaerobic glycolysis. Fatigue arises primarily from the depletion of muscle glycogen stores and the accumulation of hydrogen ions, leading to metabolic acidosis (fall in pH). - Maximal efforts of 5 to 30 minutes:
Energy comes predominantly from the aerobic metabolism of carbohydrates and fats. Declines in muscle power are linked to factors limiting mitochondrial ATP production, such as reduced acetyl-CoA supply, impaired oxidative phosphorylation, or insufficient oxygen delivery. - Submaximal prolonged efforts (>30 minutes):
Fatigue results from multiple factors including glycogen depletion, dehydration, electrolyte imbalance, elevated body temperature, and hypoglycemia. - Transitional efforts (10–30 seconds and 2–5 minutes):
Represent shifts between systems: from PCr breakdown to anaerobic glycolysis, and from anaerobic glycolysis to aerobic metabolism respectively.
Heart Rate and Energy System Contribution
Heart Rate (beats/min) | % Aerobic Contribution | % Anaerobic Contribution |
---|---|---|
<120 | 100% | – |
120–150 | 90–95% | 5–10% |
150–165 | 65–85% | 15–35% |
165–180 | 50–65% | 35–50% |
>180 | <50% | >50% |
Oxygen Transport System
The oxygen transport system ensures delivery of oxygen from the atmosphere to the mitochondria of working muscles.
- Inhalation: Atmospheric air enters the lungs.
- Gas exchange: Oxygen diffuses from alveoli into blood.
- Transport: Oxygen binds to hemoglobin within red blood cells. (Erythrocytes are produced in bone marrow under the influence of erythropoietin, a hormone secreted by the kidney.)
- Circulation: The heart pumps oxygenated blood through the vascular system.
- Capillary exchange: Oxygen diffuses into muscle fibers.
- Mitochondrial utilization: Oxygen is used to oxidize glucose and fatty acids, generating ATP along with water and carbon dioxide.
Food as an Energy Source
Nutrients provide the raw materials for ATP production. The energy released in biological reactions is ultimately measured in calories (cal).
- 1 calorie (cal): Heat required to raise the temperature of 1 g of water from 14.5°C to 15.5°C.
ATP (adenosine triphosphate) is the universal energy currency of the cell. It is constantly synthesized, broken down, and resynthesized to meet demands. Activities such as muscle contraction, tissue synthesis, nutrient transport, and thermoregulation all depend on ATP availability.
The type of substrate used depends on exercise intensity and duration:
- At rest, energy comes primarily from carbohydrates and fats.
- During mild to moderate activity, carbohydrates are increasingly used.
- In short maximal exercise, carbohydrates dominate almost exclusively.
Storage Depots of Nutrients
The body maintains specialized storage pools of macronutrients:
- Lipids (fats)
- Stored in adipose tissue as triglycerides.
- Provide the largest and most energy-dense reservoir (9 kcal/g vs ~4 kcal/g for carbohydrates or proteins).
- Efficient for storage as they do not require water binding (unlike glycogen).
- Carbohydrates
- Stored as glycogen in muscle and liver.
- Muscle glycogen is used locally, as muscle lacks the enzyme glucose-6-phosphatase and cannot release glucose into circulation.
- Liver glycogen serves as a systemic glucose reserve, especially during fasting or prolonged activity.
- Maximum glycogen storage capacity: ~15 g per kilogram of body weight.
- Proteins
- Built from 20 amino acids (9 essential, 11 non-essential).
- Primarily structural and functional (enzymes, hormones, cell proteins).
- Used as energy substrates only during prolonged fasting, illness, or extreme exercise.
- No true storage form exists; instead, proteins from skeletal muscle can be broken down into amino acids for energy if necessary.
Energy Source Hierarchy During Exercise
- High-energy phosphate compounds (ATP, PCr)
- Carbohydrates
- Lipids (fats)
- Proteins
Energy Measurement
Calorie
The most familiar unit of energy is the calorie (cal): the energy required to raise the temperature of 1 g of water by 1°C (from 14.5°C to 15.5°C).
A kilocalorie (kcal) equals 1,000 cal and is the common unit used to express the energy content of foods and the energy cost of physical activity.
Metabolic Equivalent (MET)
The metabolic equivalent (MET) expresses the metabolic rate—and therefore energy expenditure—of a given activity relative to resting metabolism.
- 1 MET ≈ oxygen uptake of 3.5 ml O₂·kg⁻¹·min⁻¹ (≈ resting energy use).
- Activities can be expressed in METs; multiplying METs × 3.5 gives VO₂ in ml·kg⁻¹·min⁻¹.
- For quick energy estimates, 1 MET ≈ 1 kcal·kg⁻¹·h⁻¹ (or ~1 kcal·min⁻¹ for a 60–70 kg adult at 10 METs ≈ ~10 kcal·min⁻¹).
Example: An activity at 10 METs corresponds to VO₂ ≈ 35 ml·kg⁻¹·min⁻¹ and ~10 kcal·min⁻¹ for an average adult.
Metabolism and Energy Production
Metabolism is the sum of all chemical reactions in the body and is divided into:
- Anabolism (biosynthesis): building macromolecules (proteins, lipids, carbohydrates, nucleic acids) from smaller units; requires ATP and reducing power (NADH, NADPH).
- Catabolism (breakdown): degrading macromolecules into smaller units; produces ATP and reducing equivalents (NADH, FADH₂, NADPH).
In healthy adults, anabolic and catabolic rates are broadly balanced over time.
Because cellular ATP stores are small, ATP must be continually resynthesized from three main sources:
- Phosphocreatine (PCr)
- Glycogen/glucose
- Cellular respiration (oxidation of carbohydrates, fats, and—when needed—proteins)
Note: 60–95% of metabolic energy is released as heat, which must be dissipated to maintain thermal balance.
Key Metabolic Molecules
ATP (Adenosine Triphosphate)
ATP is the universal energy carrier, not a long-term store. During muscle contraction, ATP → ADP + Pi releases energy; ATP must then be rapidly resynthesized.
Phosphocreatine (PCr)
PCr donates a phosphate to ADP via creatine kinase (CK) to regenerate ATP at very high rates—ideal for maximal efforts of ~5–10 s.
- Muscle contains ~4–5× more PCr than ATP (e.g., ~20 mmol PCr vs ~12 mmol creatine per kg wet muscle).
- PCr is replenished aerobically during recovery.
NAD⁺/NADH and FAD/FADH₂
- NAD⁺ (from niacin, vitamin B₃) and FAD (from riboflavin, vitamin B₂) are coenzymes that carry electrons (hydrogen) in redox reactions.
- They enable ATP production but do not themselves provide energy; excess vitamin intake does not increase ATP yield.
Acetyl-CoA
Acetyl-CoA is the central 2-carbon fuel entering the Krebs (citric acid) cycle, produced from carbohydrate, fat, and (when necessary) amino acid catabolism.
Enzymes
Enzymes are protein catalysts that accelerate reactions by lowering activation energy. The reacting molecule(s) are the substrate(s).
Major Catabolic and Anabolic Pathways
Catabolism includes:
- Glycolysis: glucose → pyruvate (with net ATP and NADH production).
- Lipid catabolism: triglycerides → glycerol + fatty acids; fatty acids undergo β-oxidation → acetyl-CoA.
- Amino acid catabolism: carbon skeletons feed into central pathways.
- Aerobic (cellular) respiration:
a. Krebs cycle (per acetyl-CoA: 3 NADH, 1 FADH₂, 1 GTP)
b. Oxidative phosphorylation (electron transport chain) → bulk ATP synthesis from NADH/FADH₂.
Anabolism comprises the biosynthesis of glycogen, triglycerides, fatty acids, and proteins from precursors.
Glycolysis
Glycolysis is a cytosolic pathway converting 1 glucose → 2 pyruvate, yielding a net 2 ATP and 2 NADH per glucose. It operates with or without oxygen:
- Anaerobic fate (fermentation):
Pyruvate → lactate (in humans) or ethanol (in yeast). Net yield remains ~2 ATP per glucose—fast but limited. - Aerobic fate:
Pyruvate → acetyl-CoA (mitochondria) → Krebs cycle → electron transport chain.
Total ATP per glucose with full aerobic oxidation is ~30–32 ATP (textbook range; varies with shuttle systems and cell type).
Key point: Glycolysis itself always nets 2 ATP per glucose. The presence of oxygen determines the fate of pyruvate and whether the cell proceeds to high-yield mitochondrial ATP production.
Catabolism and Anabolism: The Three Stages
Stage 1 – Macromolecules → building blocks
Dietary macromolecules are broken down into their monomers: proteins → amino acids, nucleic acids → nucleotides, polysaccharides → simple sugars (e.g., glucose), lipids → glycerol + fatty acids.
- Catabolism: no directly usable ATP is generated in this stage.
- Anabolism (reverse direction): requires energy (ATP) to assemble monomers into macromolecules.
Stage 2 – Building blocks → Acetyl-CoA (and related small molecules)
Monomers are further degraded to simpler intermediates; the major convergence point is acetyl-CoA. Reactions are often reversible and include many redox steps. A modest amount of ATP (or GTP) is produced in catabolism; conversely, energy is invested during anabolism. Roughly one-third of the total energy change appears here.
Stage 3 – Complete oxidation of acetyl-CoA (aerobes only)
Acetyl-CoA is fully oxidized to CO₂ and H₂O, releasing the remaining two-thirds of the energy via the citric acid (Krebs) cycle and oxidative phosphorylation. This is the cell’s principal ATP source.
The Citric Acid (Krebs) Cycle
The citric acid cycle (tricarboxylic acid, TCA) is the common final pathway for oxidation of carbohydrates, fats, and many amino acids. Although O₂ does not react in the cycle itself, the cycle operates only under aerobic conditions because NADH and FADH₂ must be re-oxidized by the electron transport chain (ETC) to regenerate NAD⁺ and FAD.
Outputs per turn (per acetyl-CoA):
- 3 NADH, 1 FADH₂, 1 GTP (≈1 ATP), and 2 CO₂.
- Most usable energy is captured indirectly in NADH and FADH₂, which power ATP synthesis during oxidative phosphorylation.
The Route into the Cycle
Cells channel fuel energy to ATP through three linked pathways:
- Glycolysis (cytosol): 10 enzyme steps convert glucose → 2 pyruvate, yielding net 2 ATP + 2 NADH.
- Anaerobic fate: pyruvate → lactate (regenerates NAD⁺).
- Aerobic fate: pyruvate → acetyl-CoA (mitochondrial pyruvate dehydrogenase) → enters the Krebs cycle.
- Citric Acid Cycle (mitochondrial matrix): acetyl-CoA is oxidized; high-energy electrons are transferred to NADH/FADH₂.
- Oxidative Phosphorylation (inner mitochondrial membrane): NADH/FADH₂ donate electrons to the ETC, driving proton pumping and ATP synthesis.
Energy Yield of the Krebs Cycle
Per acetyl-CoA oxidized: 3 NADH + 1 FADH₂ + 1 GTP.
When these reducing equivalents feed the ETC, they generate approximately:
- ~2.5 ATP per NADH and ~1.5 ATP per FADH₂ (modern P/O estimates).
Thus, per turn: ~(3×2.5) + (1×1.5) + 1 GTP ≈ 10 ATP equivalents.
Textbook note: Some older conventions use 3 ATP/NADH and 2 ATP/FADH₂; we present contemporary consensus values above.
Location & linkage: The cycle occurs in the mitochondrial matrix and is tightly coupled to the respiratory chain, which re-oxidizes NADH/FADH₂ as O₂ is reduced to H₂O.
Why the cycle matters:
- Primary provider of reducing power (NADH, FADH₂) for ATP synthesis
- Supplies biosynthetic intermediates (e.g., citrate → fatty acid synthesis; α-ketoglutarate/oxaloacetate → amino acids; succinyl-CoA → heme)
Oxidative Phosphorylation (ETC + ATP Synthase)
Oxidative phosphorylation is the dominant ATP-producing process in aerobic cells. Electrons from NADH/FADH₂ flow through multi-protein complexes of the ETC, pumping protons to create an electrochemical gradient that powers ATP synthase.
- Occurs at the inner mitochondrial membrane.
- Re-oxidizes NADH → NAD⁺ and FADH₂ → FAD, enabling continued flux through glycolysis, PDH, β-oxidation, and the Krebs cycle.
- Approximate yields: ~2.5 ATP per NADH, ~1.5 ATP per FADH₂.
Combined, the TCA + OxPhos pathways supply >95% of ATP in human aerobic metabolism.
Carbohydrate Catabolism (Summary)
- Digestion: polysaccharides → glucose, etc.
- Glycolysis: glucose → pyruvate (+ ATP, NADH).
- Aerobic: pyruvate → acetyl-CoA → TCA → ETC → ATP.
- Anaerobic: pyruvate → lactate (regenerates NAD⁺, permits rapid ATP from glycolysis).
The Cori Cycle
During intense exercise, muscle lactate enters blood → liver, where lactate dehydrogenase converts it to pyruvate, then gluconeogenesis regenerates glucose → returned to muscle. This recycles carbon but costs hepatic ATP.
Glycogen Repletion
With adequate carbohydrate intake (~8–10 g·kg⁻¹·day⁻¹), muscle glycogen can resynthesize at ~5–7% per hour, typically returning to pre-exercise levels within ~20 hours (Moogios, 1996).
Other Routes to ATP
Beyond carbohydrate oxidation, ATP also derives from:
- Aerobic lipolysis/β-oxidation: fatty acids → acetyl-CoA → TCA.
- Amino acid oxidation: carbon skeletons → acetyl-CoA or TCA intermediates (with nitrogen excreted as urea).
Lipid Metabolism (Brief)
Dietary triacylglycerols are digested to fatty acids + glycerol, re-esterified in enterocytes, and transported as chylomicrons. Fat can be stored (adipose) or oxidized: fatty acids undergo β-oxidation (liver, muscle) to acetyl-CoA, feeding the TCA. Excess carbohydrate or amino acids can be converted to fat (de novo lipogenesis). Lipids also supply phospholipids and steroids for membranes and signaling.
Protein Metabolism (Brief)
Proteins are hydrolyzed to amino acids. Surplus amino acids are not stored; they are deaminated/transaminated:
- Amino group → urea (liver urea cycle) for safe excretion.
- Carbon skeletons enter glycolysis or the TCA (some are glucogenic, some ketogenic), supporting gluconeogenesis or energy production.
Sport Examples: Dominant Energy Systems
Sport type | Predominant system |
---|---|
Power events (e.g., jumps) | ATP–PCr |
Speed events (e.g., sprints) | Anaerobic glycolysis |
Endurance (e.g., 5–10 km run) | Aerobic glycolytic |
Ultra-endurance (e.g., marathon/ultra) | Aerobic, increasingly lipolytic |