Oxidative Metabolism and Energy Systems

Mitochondria and Oxidative Metabolism

  • Oxidative metabolism involves the mitochondria.
  • Mitochondria are involved in cellular oxidation.
  • Mitochondria (plural), mitochondrion (singular).
  • Structure:
    • Outer membrane
    • Intermembrane space
    • Inner membrane
    • Cristae
    • Matrix
  • Lipid droplets are located in contact with the mitochondria, which positions the fuel source (lipid) close to where it can be broken down for ATP production.
  • Mitochondria levels differ based on muscle fiber types.
  • Physiological elements are connected, integrating physiology and applied training responses.

Transition from Glycolysis to the Krebs Cycle (TCA Cycle)

  • Krebs cycle = TCA cycle.
  • Pyruvate dehydrogenase (PDH) complex regulates glycolytic flux to the Krebs cycle.
  • Interactions with alanine.
  • Involvement in lactate production.
  • Glycogen is broken down into glucose-6-phosphate or glucose comes in directly.
  • Glycolysis produces pyruvate.
  • Pyruvate can convert to alanine or lactate via lactate dehydrogenase.
  • PDH inactive: Phosphorylation inhibits activity.
  • PDH active: Dephosphorylation activates the enzyme complex.
  • ATP is involved in PDH complex which splits to produce ADP.
  • To move PDH to inactive state:
    • Enzyme: PDH Kinase
    • High ATP:ADP ratio (plenty of cellular energy).
    • Altered NADH:NAD+NADH:NAD+ ratio.
  • To move PDH to active state:
    • Enzyme: PDH Phosphatase, which removes a phosphate group.
    • High calcium, pyruvate and insulin
  • From there it goes to Coenzyme A, citrate, and the tricarboxylic acid cycle.

Oxidative System

  • Requires oxygen for ATP production.
  • Supplies ATP at rest and during low-intensity activities.
  • ATP-PC system supplies ATP rapidly but depletes quickly (e.g., jump or short sprint).
  • Oxidative system dominates in longer duration activities.
  • No energy system supplies 100% of energy, but the oxidative system is most dominant at rest and during low-intensity activities.
  • Primarily uses carbohydrates and fats as fuel sources.
  • High-intensity anaerobic activities require anaerobic energy systems or a substantial reduction in activity intensity to allow the oxidative system to keep up.
  • Glycogen/glucose enters at the pyruvate level.
  • Fatty acids interact with acetyl coenzyme A via beta oxidation.
  • Amino acids (protein building blocks) can also supply ATP and enter the cycle at multiple stages.

Krebs Cycle Enzymes

  • Pyruvate dehydrogenase complex.
  • Citrate synthase.
  • Aconitase.
  • Isocitrate dehydrogenase.
  • Alpha-ketoglutarate dehydrogenase.
  • Key enzymes involved in the Krebs cycle process.

Energy System Substrate Supply

  • Glycogen converted to glucose.
  • Proteins broken down into amino acids.
  • Byproduct of amino acids is urea.
  • Triglycerides broken down into glycerol, fatty acids, and lactic acid which can enter at some of those stages.
  • Byproduct of this is ketone bodies.

Electron Transport Chain

  • Each turn of the Krebs cycle yields three NADH molecules and one FADH molecule.
  • Two cycles from a single glucose molecule net six NADH and two FADH.
  • Electron transport chain: carrier proteins in the inner membrane of the mitochondria.
  • Transfers electrons from NADH and FADH to oxygen.
  • Oxygen acts as an electron acceptor producing water (H2OH_2O).
  • Hydrogen atom: one proton and one electron.
  • During oxidative phosphorylation, hydrogen ions from NADH and FADH are pumped across the inner mitochondrial membrane against concentration and electrical gradients.
  • Resulting free electrons pass along the electron transport chain via complexes I through IV.
  • Hydrogen ions flow back into the mitochondrial matrix at complex V.
  • Energy released from the hydrogen ion flow powers ATP synthase to couple ADP and inorganic phosphate to regenerate ATP.

ATP Yield from Oxidative Metabolism

  • Glucose molecule yields 38 ATP.
  • Initially spend two ATP molecules to phosphorylate glucose, leaving a net yield of 36 ATP from glucose.
  • For glycogen: one less ATP is spent during initial glycolysis phases. Net ATP yield = 37.

Muscle Fiber Types and Characteristics

  • Type I: Slow-twitch = Endurance fibres.
  • Type IIa: Fast-twitch = Fast fatiguable fibers, involved in resistance training.
  • Type IIx: Explosive fibers.
  • Type I fibers:
    • Higher capillary and mitochondrial density.
    • Higher myoglobin content.
  • Type I = Higher values than Type II fibers.
  • Adequate oxygen delivery.
    • High amount of mitochondria.
    • Blood supply needed to perform oxidative metabolism.
  • Phosphorylase and PFK activity (rate-limiting enzyme) are lower.
  • Type IIa fibers have a larger capacity to store glycogen.
  • Triglyceride content is higher in Type I fibers because it can use fatty acids as a fuel source.
  • Myosin ATPase activity is important in fast rates of cross bridge cycling.
  • Phosphorylase phosphofructokinase is a major rate-limiting enzyme of phosphoryl glycolysis and is higher in Type IIa and Type IIx fibers.

Factors Limiting Oxidative Metabolism

  • Oxidative metabolism can supply large amounts of ATP over time.
  • Limiting factor: glycogen storage
  • Muscle glycogen: 300-400 grams.
    • Carb loading may increase storage.
    • Varies with muscle mass.
  • Liver: 70-100 grams.
  • Glycogen depletion rate is related to exercise intensity.
  • Muscle glycogen is more important for ATP supply during moderate to high-intensity exercise.
  • Low-intensity: oxidative metabolism uses fats fuel source in rare circumstances amino acids.
  • Glycogen can be reduced in high-intensity exercise (resistance training, repeated sprint training).
  • 50% reduction in glycogen content after a few sets and repetitions.
  • Type II fibers can store more glycogen but are more sensitive to glycogen depletion.
  • Long-duration aerobic exercise is also compromised by glycogen depletion.
  • Glycogen depletion impairs performance markedly at about 45 minutes, leading to increased perception of effort.
  • Supplementation with glycogen gels is recommended for events lasting longer than 45 mins.

Visual Representation of Glycogen Depletion

  • Before exercise: Lots of black granules (glycogen particles) around mitochondria and in different muscle regions.
  • After exercise: Fewer of these black glycogen particles.

Lipid Metabolism (7 Steps)

  1. Mobilization: Breakdown of adipose tissue and intramuscular triglycerides.
  2. Circulation: Transport of free fatty acids from adipose tissue to muscle.
  3. Uptake and entry: Free fatty acids enter the muscle from the blood.
  4. Activation: Raising the energy level of fatty acids to prepare for breakdown.
  5. Translocation: Entry of fatty acids into the mitochondria.
  6. Beta oxidation: Production of acetyl coenzyme A from activated fatty acids + reducing equivalents (NADH and FADH).
  7. Mitochondrial oxidation: Krebs cycle and electron transport chain activity ATP production.
  • Most lipid oxidized in muscle during exercise is delivered by circulating blood.
  • Blood contains free fatty acids released from adipose tissue after mobilization of triglyceride stores by activation of hormone-sensitive lipase.
  • Blood also contains lipoproteins that deliver a smaller lipid quantity to muscle during exercise.
  • Ability to use fats as a fuel source depends on arterial blood flow and muscle blood flow.
  • Before oxidation or storage as triglyceride, fatty acids delivered by circulation must be activated.
  • Activation step: ATP molecule that joins with coenzyme A.
  • To enter mitochondrial matrix, activated fatty acid must combine with carnitine.
  • Carnitine acyltransferase I and II enzymes facilitate formation/dissociation of fatty acyl carnitine complex and release of activated fatty acid into the matrix.

Carbohydrate vs. Fat Storage

  • Carbohydrate:
    • Muscle glycogen: 0.4 kg
    • Liver: 100 g
    • Blood plasma: very small amount
  • Fat:
    • Adipose tissue = ~10 kg

Protein Metabolism

  • Protein (amino acids) is also used in oxidative metabolism to produce ATP.
  • Amino acids enter the TCA/Krebs cycle at various stages:
    • Alanine, cysteine, glycine, serine, and theanine convert to pyruvate, acetyl coenzyme A, and then enter the Krebs cycle.
    • Isoleucine, leucine, and tryptophan goes through acetyl coenzyme A step and then enter to TCA cycle.

Glucose-Alanine Cycle

  • Proposed by Cahill.

  • Complements the Cori cycle and lactate shuttle.

  • Transports carbon atoms from skeletal muscle to liver for gluconeogenesis.

  • Branched-chain amino acids (mainly leucine) provide nitrogen for amino acid formation in muscle.

  • Carbon source for alanine formation is glycolytic.

  • Muscle:

    • Glycogenolysis.
    • Glycolysis pyruvate.
    • Amino acids.
    • Byproduct of alanine enters into circulation.

  • Liver:

    • Gluconeogenesis.
    • Plasma protein.
    • Byproduct of NH3NH_3, then urea.

  • Urea is excreted via the kidneys.

  • Muscle amino acids provide both nitrogen and carbon precursors to alanine in situations such as starvation and prolonged exercise

  • Amino acid usage in oxidative metabolism is more pronounced in starvation conditions. The body goes to protein reserves for extreme situations.

  • Preference for glycogen.

  • Fat reserves can degrade into free fatty acids to be used.

  • Protein metabolism is the last resort in extreme situations (such as starvation or prolonged exercise).