topic 7: adaptation of metabolic enzymes

1. Changes Are Not Due to an Increase in Specific Activities (Per Unit of Mitochondrial Protein)

• This means that the observed metabolic changes are not simply because individual enzymes are working harder or becoming more efficient.

• Instead, the changes occur primarily due to an increase in mitochondrial content (more mitochondria per cell), leading to greater overall metabolic capacity.

• This is a key adaptation to endurance training, where mitochondria proliferate in response to sustained energy demands.

2. Increased Capacity to Transfer Electrons from Cytosolic NADH to Mitochondrial Electron Carriers

• Why does this matter? Cells generate NADH during glycolysis, but NADH itself cannot directly cross the mitochondrial membrane.

• To transfer electrons from NADH into the mitochondria (so they can enter the electron transport chain for ATP production), cells rely on shuttle systems:

  a. Malate-Aspartate Shuttle (Heart, Liver, Slow-Twitch Muscle Fibers)

  • Involves malate and aspartate as carriers.

  • More efficient, as it directly transfers electrons to NADH inside the mitochondria, preserving energy.

  • This shuttle is dominant in aerobic tissues like the heart and slow-twitch muscle fibers because they rely more on oxidative metabolism.

  b. Glycerol-Phosphate Shuttle (Fast-Twitch Muscle)

  • Uses glycerol-3-phosphate to shuttle electrons.

  • Transfers electrons to FADH2 instead of NADH, which yields slightly less ATP.

  • Found more in fast-twitch muscle fibers, which rely more on anaerobic metabolism.

• Adaptation:

  • The increased function of these shuttles means cytosolic NADH is more efficiently used in oxidative metabolism, reducing reliance on anaerobic glycolysis (which produces lactate).

3. Increased Capacity for the Alanine Transaminase Reaction

• What is this reaction?

  • Alanine transaminase (ALT) converts pyruvate + glutamate → alanine + α-ketoglutarate.

  • Alanine can leave the muscle and be transported to the liver, where it is converted back into pyruvate for gluconeogenesis (Cori Cycle).

• Why does this matter?

  • If more pyruvate is converted to alanine, it means less pyruvate is available for lactate production (which occurs via lactate dehydrogenase, LDH).

  • This adaptation helps reduce lactate accumulation and improve metabolic efficiency during endurance exercise.

4. No Major Change in Glycolytic Capacity, but Increased Hexokinase & Glycogen Synthase Activity

• Glycolytic capacity refers to the ability of cells to break down glucose anaerobically.

• This suggests that the overall rate of glycolysis does not increase significantly.

• However, two key enzymes do increase:

  a. Hexokinase (HK) Activity Increases

  • Hexokinase phosphorylates glucose to glucose-6-phosphate (G6P) in the first step of glycolysis.

  • Increased HK activity means glucose is trapped inside the cell more efficiently, improving glucose uptake and utilization.

  • This is an adaptation that enhances glucose availability for both glycolysis and glycogen synthesis.

  b. Increased Glycogen Synthase Activity

  • Glycogen synthase is responsible for making glycogen from G6P.

  • This allows muscles to store more glycogen, providing a better fuel reserve for prolonged exercise.

• Why does this matter?

  • Even though glycolytic capacity doesn’t change much, these adaptations ensure that glucose uptake and storage are optimized, making muscles more resistant to fatigue.

5. Slight Decrease in Total Lactate Dehydrogenase (LDH) Activity with an Isoform Shift

• LDH catalyzes the conversion of pyruvate to lactate (anaerobic metabolism).

• With endurance adaptations, there is a slight decrease in total LDH activity, meaning the muscle relies less on anaerobic glycolysis.

• LDH Isoform Shift: From M-LDH (Muscle) to H-LDH (Heart)

  • M-LDH (LDH-M or LDH-5):

    • Found in fast-twitch muscle fibers

    • Favors lactate production from pyruvate (anaerobic metabolism).

  • H-LDH (LDH-H or LDH-1):

    • Found in heart and slow-twitch muscle fibers

    • Favors the conversion of lactate back to pyruvate, which can then enter the mitochondria for oxidative metabolism.

• Why does this matter?

  • This shift means muscles become better at oxidizing lactate instead of just producing it, improving endurance.

  • Lactate is no longer just a "waste product"—it becomes a valuable energy source that can be shuttled to mitochondria for further ATP production.

B) fat metabolism

1. Endurance Training Can Double Mitochondrial Capacity, Enhancing Fat Utilization

• What this means:

  • Endurance training increases mitochondrial density and function, effectively doubling the oxidative capacity of muscle.

  • This adaptation enhances the ability to use fat as a primary energy source, reducing reliance on glycogen stores.

• Why does fat utilization increase?

  • Increased mitochondrial enzymes (e.g., β-oxidation enzymes like carnitine palmitoyltransferase, CPT-1).

  • Greater blood flow and capillarization, improving fatty acid transport into muscles.

  • Enhanced reliance on intramuscular triglycerides (IMTG) as a fuel source.

• Physiological significance:

  • Greater fat oxidation at a given intensity spares glycogen, delaying fatigue in prolonged exercise.

  • This shift helps endurance-trained athletes maintain performance over longer durations.

2. Endurance Training Increases Lipoprotein Lipase (LPL) Activity (Fiber-Type Specific)

• What does LPL do?

  • Lipoprotein lipase (LPL) hydrolyzes triglycerides (TGs) in lipoproteins, releasing free fatty acids (FFAs) for muscle uptake and oxidation.

  • Higher LPL activity means more fat is available for energy production.

• Fiber-type specificity:

  • LPL activity increases more in slow-twitch (Type I) fibers, which rely on oxidative metabolism.

  • Fast-twitch (Type II) fibers show less of an increase since they rely more on glycogen metabolism.

• Why does this matter?

  • This adaptation enhances the ability to mobilize and oxidize fat, further reducing glycogen depletion during prolonged exercise.

3. Other Changes in Oxidative Phosphorylation (O/P) Capacity

• Oxidative phosphorylation (O/P) = ATP production in mitochondria via the electron transport chain (ETC).

• Endurance training leads to increased enzyme activities and cytochrome content, including:

  • ↑ Cytochrome c and cytochrome oxidase (Complex IV) → improves electron transport efficiency.

  • ↑ Succinate dehydrogenase (SDH, Complex II) and citrate synthase (TCA cycle enzymes) → boosts aerobic metabolism.

• Why does this matter?

  • More mitochondria + increased O/P capacity = greater ATP production efficiency.

  • This supports higher energy demands without excessive lactate production, improving endurance performance.

4. VO₂ Remains the Same at Absolute Submaximal Workloads, But There Is Less Glycogen Depletion and Lactate Production

• What does this mean?

  • At the same absolute submaximal intensity, VO₂ (oxygen consumption) remains unchanged, but:

    • Less glycogen is used.

    • Less lactate is produced.

    • ATP production and O/P are more tightly coupled.

• Why does this happen?

  • More mitochondria → better ability to generate ATP aerobically.

  • Greater fat oxidation → reduces glycogen demand.

  • More efficient NADH oxidation → less reliance on anaerobic glycolysis (which produces lactate).

• Key physiological benefit:

  • At the same workload, trained individuals can sustain exercise longer before depleting glycogen, reducing fatigue.

5. Increased Aerobic Enzyme Capacity and Submaximal Exercise Duration, but No Increase in VO₂max

• Aerobic enzyme capacity increases:

  • Enzymes involved in β-oxidation, the TCA cycle, and the electron transport chain all show higher activity.

  • This leads to greater ATP production at submaximal workloads.

• Submaximal endurance improves, but VO₂max does not

  • Why? VO₂max is largely limited by cardiovascular factors (e.g., max cardiac output, hemoglobin levels, oxygen delivery).

  • Endurance training enhances metabolic efficiency at submax levels, but does not necessarily increase maximal oxygen uptake beyond initial improvements.