Section 4. Fuel oxidation, generation of ATP

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Section 4. Fuel oxidation, generation of ATP

• Section 4. Overview of
• Fuel oxidation, ATP generation
• Physiological processes require energy
• transfer from chemical bonds in food
• Electrochemical gradient
• Movement of muscle
• Biosynthesis of complex molecules
• 3 phases
• Oxidation of fuels (carbs, fats, protein)
• Conversion of energy to PO4 of ATP
• Utilization of ATP to drive energy-requiring
  reactions

Fig.iv.1
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Fuel oxidation overview - respiration

• Phase 1 energy (e-) from fuel transfer to NAD
  and FAD
• Acetyl CoA, TCA intermediates are central
  compounds
• Phase 2 electron transport chain convert e- to
  ATP
• membrane proton gradient drives ATP synthase
• Phase 3 ATP
• powers processes

Fig. iv.2
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Respiration occurs in mitochondria

• Respiration occurs in mitochondria
• Most enzymes in matrix
• Inner surface has
• e- transport chain
• ATP synthase
• ATP transported through
• inner membrane,
• diffuses through outer
• Some enzymes encoded
• by mitochondrion genome,
• most by nuclear genes

Fig. iv.3
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Glucose is universal fuel for every cell

• Glycolysis is universal fuel
• 1 glucose -gt 2 pyruvate 2 NADH 2 ATP
• Aerobic path
• Continued oxidation
• Acetyl CoA -gt TCA,
• NADH, FAD(2H) -gt e- transport chain
• Lots of ATP
• Anaerobic fermentation
• anaerobic glycolysis
• Oxidation of NADH to NAD
• Wasteful reduction of pyruvate
• to lactate in muscles
• to ethanol, CO2 by yeast

Fig. iv.4
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Chapt. 19 Cellular bioenergetics of ATP, O2

• Ch. 19 Cellular bioenergetics
• Student Learning Outcomes
• Explain the ATP-ADP cycle
• Describe how chemical bond energy of fuels can do
  cellular work through PO4 bond of ATP
• Explain how NADH, FAD(2H) coenzymes carry
  electrons to electron transport chain
• Describe how ATP synthesis is endergonic
  (requires energy)
• Describe how ATP hydrolysis (exergonic) powers
  biosynthesis, movement, transport

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Fuel oxidation makes ATP

• Cellular Bioenergetics of ATP and O2
• Chemical bond energy of fuels transforms to
  physiological responses necessary for life
• Fuel oxidation generates ATP
• ATP hydrolysis provides energy for most work
• High energy bonds of ATP
• Energy currency of cell

Fig. 19.1
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ATP

• High energy phosphate bond of ATP
• Strained phosphoanhydride bond
• DG0 -7.3 kcal/mol standard conditions
• Hydrolysis of ATP to ADP Pi transfers PO4 to
  metabolic intermediate or protein, for next step

Fig. 19.2
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Thermodynamics brief

• Thermodynamics states what is possible
• DG change in Gibbs free energy of reaction
• DG DG0 RT ln P/S (R gas const T
  temp oK)
• DG0 DG at standard conditions of1 M substrate
  product and proceeding to equilibrium)
• DG0 DG0 under standard conditions of H2O
  55.5 M,
• pH 7.0, and 25oC 37oC not much different
• Concentrations of substrate(s) and products(s)
• At equilibrium, DG 0, therefore
• DG0 -RT lnKeq -RT lnP/S

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Thermodynamics brief

• Thermodynamics states what is possible
• Exergonic reactions give off energy (DG0 lt 0)
• typically catabolic
• Endergonic reactions require energy (DG0 gt 0)
• typically anabolic
• Unfavorable reactions are coupled to favorable
  reactions
• Hydrolysis of ATP is very favorable
• Additive DG0 values determine overall direction

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C. Exogonic, endogonic reactions

• Phosphoglucomutase converts G6P to/from G1P
• G6P to glycolysis
• G1P to glycogen synthesis
• Equilibrium favors G6P
• Exergonic reactions give off energy (DG0 lt 0)
• Endergonic reactions require energy (DG0 gt 0)

Fig. 19.3
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III. Energy transformation for mechanical work

• ATP hydrolysis can power muscle movement
• Myosin ATPase hydrolyzes ATP, changes shape
• ADP form changes shape back, moves along
• Actin was activated by Ca2

Fig. 19.4
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ATP powers transport

• Active transport ATP hydrolysis moves
  molecules
• Na, K ATPase sets up ion gradient bring in
  items
• Vesicle ATPases pump protons into lysosome
• Ca2-ATPases pump Ca2 into ER, out of cell

Fig. 10.6
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III. ATP powers biochemical work

• ATP powers biochemical work, synthesis
• Anabolic paths require energy DGo additive
• Couple synthesis to ATP hydrolysis
• Phosphoryl transfer reactions
• Activated intermediate
• Ex. Table 19.3
• glucose Pi -gt glucose 6-P H2O 3.3
  kcal/mol
• ATP H2O -gt ADP Pi - 7.3 kcal/mol
• Sum glucose ATP -gt glucose 6-P ADP -4.0
• Also Glucose -gt G-1-P will be -2.35 kcal/mol
  overall
• hydrolysis of ATP, through G-6-P to G-1-P

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Activated intermediates in glycogen synthesis

• Glycogen synthesis needs 3 P
• Phosphoryl transfer to G6P
• Activated intermediate with UDP covalently linked

Fig. 19.5
Fig. 19.6
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DG depends on substrate, product concentrations

• DG depends on substrate, product concentrations
• DG DG0 RT ln P/S
• Cells do not have 1M concentrations
• High substrate can drive reactions with positive
  DG0
• Low product (removal) can drive reactions with
  positive DG0
• Ex., even though equilibrium (DG0 1.6
  kcal/mol)
• favors G6P G1P in a ratio 94/6,
• If G1P is being removed (as glycogen synthesis),
  then equilibrium shifts
• ex. If ratio 94/3, then DG -0.41 favorable

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Activated intermediates with bonds

• Other compounds have high-energy bonds to aid
  biochemical work (equivalent to ATP)
• UTP, CTP and GTP also (made from ATP NDP)
• UTP for sugar biosyn, GTP for protein, CTP for
  lipids
• Some other compounds
• Creatine PO4 energy reserve muscle, nerve, sperm
• Glycolysis
• Ac CoA TCA cycle

Fig. 19.7
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V. Energy from fuel oxidation

• Energy transfer from fuels through oxidative
  phosphorylation in mitochondrion
• NADH, FAD(2H) transfer e- to O2
• Stepwise process through
• protein carriers
• Proton gradient created
• e- to O2 -gt H2O
• ATP synthase makes ATP
• lets in H

Fig. 19.8
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Oxidation/reduction

• Oxidation reduction reactions
• Electron donor gets oxidized recipient is
  reduced
• LEO GER
• Loss Electrons oxidation gain electrons is
  reduction
• use coenzyme e- carriers

Fig. 19.9 NADH
Fig. 19.10 FAD(2H)
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Redox potentials

• Redox potentials indicate energetic possibility
• Energy tower combine half reactions for overall
• Ex. Table 19.4
• ½ O2 2H 2e- -gt H2O E0 0.816
• NAD 2H 2e- -gt NADH H -0.320
• Combine both reactions (turn NADH -gt NAD)
  0.320
• Total 1.136 (very big) -53 kcal/mol
• FAD(2H) gives less, since its only 0.20 (FAD(2H)
  -gt FAD

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Calorie content of fuels reflects oxidation state

• Calorie content of fuels reflects oxidation
  state
• C-H and C-C bonds will be oxidized
• Glucose has many C-OH already
• 4 kcal/g
• Fatty acids very reduced
• 9 kcal/g
• Cholesterol no calories
• not oxidized in reactions giving NADH

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Anaerobic glycolysis fermentation

• Anaerobic glycolysis fermentation
• In absence of O2, cell does wasteful recycling
• NADH oxidized to NAD (lose potential ATP)
• pyruvate reduced to lactate
• glycolysis can continue with new NAD
• yeast makes ethanol,
• CO2 from pyruvate
• bacteria make diverse
• acids, other products

Fig. 19.11
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Oxidation not for ATP generation

• Most O2 used in electron transport chain.
• Some enzymes use O2 for substrate oxidation,
• not for ATP generation
• Oxidases transfer e- to O2
• Cytochrome oxidase in
• electron transport chain
• Peroxidases in peroxisome
• Oxygenases transfer e-
• and O2 to substrate
• Form H2O and S-OH
• Hydroxylases
• (eg. Phe -gt Tyr)

Fig. 19.12
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VII Energy balance

• Energy expenditure reflects oxygen consumption
• Most O2 is used
• by ATPases

Fig. 19.14
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Energy balance

• Portion of food metabolized is related to energy
  use
• Basal metabolic rate
• Thermogenesis
• Physical activity
• Storage of excess
• If you eat to much
• and dont exercise,
• you will get fat
• (summarizes ATP-ADP cycle)