Aerobic Overview

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Aerobic Overview

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Electron Transport System Complex

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The Electron Transport Chain

• Located on the mitochondrial inner membrane
• Oxidative Phosphorylation refers to two
  separate processes that usually function together
• Oxidation spontaneous process coupled with
  phosphorylation
• Phosphorylation is an endergonic process driven
  by oxidation
• Function of ETC - reducing equivalents containing
  a high-energy hydrogen and electron pair - gain
  entry into chain.

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Function of the ETC

• Each constituent can exist in
• Reduced (higher energy, with electron)
• Oxidized (lower energy, without electron)
• Constituents are sequentially arranged in close
  proximity on the inner membrane
• Constituents are arranged such that the redox
  potential of each constituent is greater (more
  positive)
• Thus electrons move from NADH (electronegative)
  to atomic oxygen (electropositive)

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Control of ETC

• ADP stimulates ETC
• ATP inhibits ETC
• Brooks states the control of muscle metabolism is
  elegantly simple
• As soon as muscle contracts, ATP is split and ADP
  is formed
• Relative amounts of ADP and ATP set in motion
  biochemical events to reform ATP
• When exercise stops, respiration reestablishes
  normal levels of ATP, ADP, AMP

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Oxidative Phosphorylation

• Protons are translocated across the membrane,
  from the matrix to the intermembrane space
• Electrons are transported along the membrane,
  through a series of protein carriers
• Oxygen is the terminal electron acceptor,
  combining with electrons and H ions to produce
  water
• As NADH delivers more H and electrons into the
  ETS, the proton gradient increases, with H
  building up outside the inner mitochondrial
  membrane, and OH- inside the membrane.

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Oxidative Phosphorylation

• Protons are translocated across the membrane,
  from the matrix to the intermembrane space, as a
  result of electron transport resulting from the
  formation of NADH by oxidation reactions. (See
  the animation of electron transport.) The
  continued buildup of these protons creates a
  proton gradient.
• ATP synthase is a large protein complex with a
  proton channel that allows re-entry of protons.
• ATP synthesis is driven by the resulting current
  of protons flowing through the membraneADP Pi
  ---gt ATP

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Lipid Metabolism

• A variety exist in diet (triglycerides)
• High energy content, efficient storage
• Liver, adipose tissue, skeletal muscle-almost
  inexhaustible fuel supply
• Process of lipid utilization is slow to be
  activated rate is slower than CHO catabolism
• Small ? in ability to use fat effectively slows
  sugar CHO metabolism

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Lipid Defined

• Not soluble in water
• Fatty acids are long-chain carboxylic acids
• Linked to glycerol
• Triglycerides make up the majority of lipid and
  calories taken into stored in body

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Oxidation of Saturated Fatty Acids

• Beta Oxidation, occurs in matrix of mitochondrion
• Fatty acylCoA appears in matrix in repeated
  cycles (activated fatty acid)
• With each cycle, fatty acyl CoA, shortened by 2
  carbon atoms acetyl CoA.
• Each cycle results in 2 pair of hydrogen
  electrons picked up by FAD and NAD acetyl CoA
  (2-carbon compound)

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Lipid Metabolism

• High energy content of triglycerides
• Vast, efficient storage reserve
• Provide an almost inexhaustible fuel supply for
  muscular exercise
• Processes for lipid utilization are slow to be
  activated proceed at rates significantly slower
  than CHO catabolism
• Fat metabolism a purely aerobic process
• Best developed in heart and red skeletal muscle
  fibers

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Utilization of Lipids During Exercise

• Mobilization - the breakdown of adipose and
  intramuscular triglyceride (LPL, HSL)
• Circulation - the transport of free fatty acids
  (FFAs) from adipose to muscle
• Uptake - the entry of FFAs into muscles from
  blood
• Activation - raising the energy level of fatty
  acids preparatory to catabolism
• Translocation - the entry of activated fatty
  acids into mitochondria
• ? Oxidation - the catabolism of acetyl-CoA of
  activiated fatty acids and the production of
  reducing equivalents (NADH FADH)
• Mitochondrial oxidation - Krebs cycle and
  electron transport chain activity

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Utilization of Lipids During Exercise

• Circulation - a key to lipid oxidation during
  exercise is arterial level of FFAs
• Enhancement of cardiac output and muscle blood
  flow
• Uptake - Fatty acid binding protein (FABP)
• Sarcolemmal fatty acid binding protein (S-FABP)
• Transport fatty acids throughout the cell

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Utilization of Lipids During Exercise

• Activation - raises the fatty acids to a higher
  level involves ATP coenzyme A (CoA) (like
  first step in glycolysis)
• Fatty acid becomes attached to CoA derivative,
  termed fatty acyl-CoA
• Site of fatty acyl-CoA formation is the inner
  mitochondrial membrane
• Mitochondrial membrane is selectively permeable -
  therefore, need transport mechanism

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Utilization of Lipids During Exercise

• FA use carrier, carnitine and carnitine
  transferase enzymes
• CoA stripped off forming fatty acyl-carnitine and
  moves across the membrane
• On inner side, carnitine transferaes 2 catalyzes
  the reverse reaction, leaving carnitine within
  membrane and releasing Fatty-acyl CoA into
  mitochondrial matrix

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Free Fatty Acid Levels in Blood During Rest and
Exercise

• REST
• FFA levels are less than 1mM
• FFA levels are double that of rest following
  36-hour fast
• EXERCISE
• Increase FFA levels occur during mild to moderate
  intensity
• Triglyceride synthesis promoted with severe
  intensity exercise

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Lipid Mobilization

• Lipoprotein lipase in adipose tissue (LPL)
• In capillary wall stimulated by insulin and
  glucose promotes fat storage
• Hormone sensitive lipase (HSL) stimulates fat
  breakdown, is inhibited by insulin, and is
  stimulated by other hormones including
  epinephrine, norepinephrine and growth hormone.
• Control and action of these two lipases are
  reversed
• Catacholamine release is rapid initiation of
  lipolysis at exercise onset
• Growth hormone levels take 10-15 minutes to
  increase maintenance of lipolysis during
  prolonged exercise.
• Insulin inhibits HSL

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Circulation and Uptake

• Uptake
• Half arterial FFAs are removed from muscle
  capillary bed during each circulation of blood
  through muscle.
• Key to lipid oxidaton during exercise is arterial
  level of FFAs
• Rate of blood flow
• Sarcolemmal fatty acid binding protein (S-FABP)
  transports fatty acids throughout cell
• Circulation

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Activation and Translocation

• The activation process raises the fatty acids to
  a higher energy level and involves ATP
• Fatty acid is attached to coenzyme A---gt fatty
  acyl-CoA
• Fatty acyl-CoA formation occurs in cytoplasm
• Translocation --gt involves translocation of fatty
  acid derivatives into the mitochondrial
  organelles (where fats can be oxidized)
• Carnitine is carrier of activated fatty acid
• Carnitine translocase catalyzes carrier reaction

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Fatty Acid Translocation

• Malonyl-CoA inhbits Carnitine transferase
• Malonyl-CoA is an intermediate of fatty acid
  synthesis
• Malonyl-CoA concentration declines during
  moderate intensity exercise---gtwhich is
  associated with an increase in the rate of lipid
  oxidation (Activates carnitine transferase)
• The above occurs in the heart, not certain if
  occurs in skeletal muscle

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Lipid Metabolism Enzymes

• Adipose tissue
• Capillary wall Lipoprotein lipase after meal,
  bld glucose high, insulin high, glucagon low ?
  enzyme is activated promotes fat storage
• Hormone sensitive lipase stimulates fat
  breakdown, inhibited by insulin, stim by epi and
  norepinephrine
• Muscle tissue
• Lipoprotein lipase is hormone sensitive and
  operates like adipose hormone-sensitive lipase
  termed
• Type L-HSL inhibited by high levels of insulin
  and stimulated by glucagon similar to adipose
  HSL.

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Crossover Concept

• Power output most important factor in determining
  fuels used during exercise
• Intensity progresses from mild-moderate-hard
  intensities, fuel mix switches from lipid to
  carbohydrate
• Resting, postabsorptive state
• 60 - lipid oxidation
• 35 - carbohydrate
• 05 - protein

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Crossover Concept

• Exercise/contractions start
• GLUT 4 is translocated to sarcolemma
• Phosphorylase is activated by high Ca
• Combined with abundance of glycolytic enzymes and
  high reaction rates ?rapid glycolysis
• Arterial FFA fall as lipolysis is inhibited by
  lactic acidosis
• Lipid utilization during recovery is essential to
  allow individual to function normally and replace
  muscle glycogen

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Utilization of Lipids during Exercise