Site of Aerobic Metabolism

1
Site of Aerobic Metabolism
2
Mitochondria

• Cellular oxidation takes place here
• Pyruvate, lactate, products of lipid amino acid
  metabolism
• Oxygen consumed and ADP phosphorylated inside
  mitochondria
• Mitochondria appear in two places in skeletal
  muscle
• Subsarcolemmal -Immediately beneath sarcolemma
  in position to receive O2 from arterial
  circulation
• Intermyofibrillar mitochondria exist among the
  contractile elements

3
Mitochondrion

• Outer membrane acts as barrier allows small
  molecules to freely move in
• Inner membrane space contains enzymes for
  exchange transport
• Cristae (many folds) where oxidative
  phosphorylation occurs

4
Mitochondrion

• F Complex actual site of phosphorylation
• F0 stalk
• F1 ball
• Matrix contains mitochondrial protein LDH and
  Krebs cycle enzymes

5
Citric Acid Cycle

• Prime Function oxidize acetyl groups resulting
  in ATP formation
• Electrons are removed from acetyl groups
  attaches them to NAD or FAD which feed into the
  electron transport chain
• Carbon atoms of acetyl group are released as CO2
• Oxidation of acetyl CoA accounts for about two
  thirds of the ATP formation oxygen consumption
  in mammals

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Krebs Cycle

• ATP
• GTP
• CO2
• H2
• H2O

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Krebs Cycle
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Regulation of the Citric Acid Cycle

• High levels of NADH inhibit 3 key reactions
  substrate availiability
• isocitrate dehydrogenase (rate-limiting enzyme
  (stimulated by ADP)
• alpha-ketoglutarate dehydrogenase
• citrate synthase
• Insulin binding promotes dephosphorylation
  (activation) of pyruvate dehydrogenase (PDH)

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Pyruvate Dehydrogenase (PDH)

• Phosphorylation inhibits PDH
• ATP/ADP, Acetyl-CoA/CoA, and NADH/NAD -- act
  to reduce glycolytic flux to the Krebs Cycle by
  inactivation of PDH
• Dephosphorylation of PDH activates enzyme as well
  as high Ca, decreases inATP/ADP,
  Acetyl-CoA/CoA, and NADH/NAD
  
  

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Control Regulation of Metabolic Pathways

• Energy state regulation
• ATP, ADP levels activate or deactivate regulatory
  enzymes
• Quick response linked to energy expenditure
• Hormone amplification
• Cyclic-AMP levels on inside surfaces of target
  membranes
• Slower but more persistent and widespread
• Substrate/Enzyme regulation
• NADHH builds up, activates lactate dehydrogenase
  converting more pyruvate to LA

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Enzymatic Regulation of Metabolism

• Lower the energies of activation
• Spontaneous reactions to proceed
• Modulators
• Stimulators Inhibitors
• ATP a classic inhibitor
• ADP, Pi usually stimulators
• NADH/NAD ratio

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Enzymatic Regulation

• Adenine nucleotide charge regulates both
  glycolysis and the Krebs cycle
• ATP and ADP, respectively, stimulate and inhibit
  the ETC.
• Small decrements in the adenine energy charge
  activate ATP-yielding systems

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Hormone Amplification

• Epi, Glucagon along w/Cortisol - stimulate liver
  to convert a.a. to glucose
• Insulin and glucose inhibits the above hormones

14
Substrate/Enzyme Regulation

• Less immediate but powerful effects
• NADHH build-up occurs during very high energy
  demands
• Oxidation capacity has been exceeded
• High energy demands increases rate of pyruvate
  production ---gt increased activity of pyruvate
  dehydrogenase (PDH) which controls entry into
  Krebs cycle

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Oxidative State Regulation

• Oxygen availability, deprivation
• With oxygen available, ADP available, cytochrome
  oxidase (CO) is activated
• speeds up hydrogen combination w/O2
• Frees up FAD and NAD while ATP is formed
• Oxygen low during exercise, CO is inhibited with
  back-up of NADHH and FADH2, ADP
• Serve as clear signals that Anaerobic glycolysis
  will be predominant supplier of ATP
• The key determining factor is exercise intensity

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Comparing the Energy Systems

• System Max Power Max
  Capacity
• (moles/min of ATP) (total
  moles of ATP)
• ATP
  ATP
• Phosphagen 3.6
  0.7
• Lactic Acid System 1.6
  1.2
• Oxygen System 1.0
  90.0
• (from glucose)

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Anaerobic Glycolysis
(Lactic Acid System)

• Per kg muscle
  Total Muscle
• Max LA (grams) 2.0 - 3.0
  60-70
• ATP Formation (mM) 33 - 38 1000-1200
• Useful Energy (kcal) .33 - .38 10
  - 12