Section 4. Fuel oxidation, generation of ATP
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
Section 4. Overview of
Fuel oxidation, ATP generation:
Physiological processes require energy
transfer from chemical bonds in food:
•
•
•
Phase 3: ATP
powers processes
Electrochemical gradient
Movement of muscle
Biosynthesis of complex molecules
3 phases:
• Oxidation of fuels (carbs, fats, protein)
Fig.iv.1
• Conversion of energy to ~PO4 of ATP
• Utilization of ATP to drive energy-requiring reactions
Respiration occurs in mitochondria
Glucose is universal fuel for every cell
Respiration occurs in mitochondria:
Glycolysis is universal fuel:
1 glucose -> 2 pyruvate + 2 NADH + 2 ATP
• Most enzymes in matrix
• Aerobic path:
• 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.2
Continued oxidation
Acetyl CoA -> TCA,
NADH, FAD(2H) -> e- transport chain
Lots of ATP
• Anaerobic: fermentation:
Fig. iv.3
• ‘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
ATP
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
Thermodynamics brief
High energy phosphate bond of ATP:
• Strained phosphoanhydride bond
• ∆G0’ -7.3 kcal/mol standard conditions
• Hydrolysis of ATP to ADP + Pi transfers PO4 to
metabolic intermediate or protein, for next step
Thermodynamics states what is possible:
∆G = change in Gibbs free energy of reaction:
∆G = ∆G0 + RT ln [P]/[S] (R = gas const; T = temp oK)
∆G0 = ∆G
∆ at standard conditions of1 M substrate & product
and proceeding to equilibrium)
∆G0’ = ∆G0 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, ∆G = 0, therefore
Fig. 19.2
∆G0’ = -RT lnKeq’ = -RT ln[P]/[S]
2
Thermodynamics brief
C. Exogonic, endogonic reactions
Thermodynamics states what is possible:
• Exergonic reactions give off energy (∆G0’ < 0)
• typically catabolic
• Endergonic reactions require energy (∆G0’ > 0)
• typically anabolic
• Unfavorable reactions are coupled to favorable
reactions
• Hydrolysis of ATP is very favorable
• Additive ∆G0’ values determine overall direction
Phosphoglucomutase
converts G6P to/from G1P:
• G6P to glycolysis
• G1P to glycogen synthesis
• Equilibrium favors G6P
Exergonic reactions give off
energy (DG0’ < 0)
Endergonic reactions
require energy (DG0’ > 0)
Fig. 19.3
III. Energy transformation for mechanical work
ATP powers transport
ATP hydrolysis can power muscle movement:
• Myosin ATPase hydrolyzes ATP, changes shape
• ADP form changes shape back, moves along
• Actin was activated by Ca2+
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. 19.4
Fig. 10.6
3
III. ATP powers biochemical work
Activated intermediates in glycogen synthesis
ATP powers biochemical work, synthesis:
Glycogen synthesis needs 3 ~P:
Anabolic paths require energy: ∆Go’ additive
• Couple synthesis to ATP hydrolysis:
• Phosphoryl transfer to G6P
Phosphoryl transfer reactions
• Activated intermediate
•
• Activated intermediate with
UDP covalently linked
Fig. 19.5
Ex. Table 19.3:
glucose + Pi -> glucose 6-P + H2O + 3.3 kcal/mol
ATP + H2O -> ADP + Pi
- 7.3 kcal/mol
Sum: glucose + ATP -> glucose 6-P + ADP -4.0
Also Glucose -> G-1-P will be -2.35 kcal/mol overall:
hydrolysis of ATP, through G-6-P to G-1-P
∆G depends on substrate, product concentrations
∆G depends on substrate, product concentrations
∆G = ∆G0 + RT ln [P]/[S]
• Cells do not have 1M concentrations
• High substrate can drive reactions with positive ∆G0’
• Low product (removal) can drive reactions with positive ∆G0’
Fig. 19.6
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):
•
•
•
• Ex., even though equilibrium (∆G0’= +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 ∆G = -0.41 favorable
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
Oxidation/reduction
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 -> H2O
• ATP synthase makes ATP
• lets in H+
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)
Fig. 19.8
Redox potentials
Calorie content of fuels reflects oxidation state
Redox potentials indicate energetic possibility:
Calorie content of fuels reflects oxidation state:
Energy tower; combine half reactions for overall:
• C-H and C-C bonds will be oxidized:
Ex. Table 19.4:
• Glucose has many C-OH already:
• 4 kcal/g
½ O2 + 2H+ + 2e- -> H2O
NAD+ + 2H+ + 2e- -> NADH + H+
E0’ 0.816
-0.320
Combine both reactions (turn NADH -> NAD+) = 0.320
• Fatty acids very reduced:
9 kcal/g
Total 1.136 (very big) = -53 kcal/mol
• Cholesterol no calories:
FAD(2H) gives less, since its only +0.20 (FAD(2H) -> FAD
not oxidized in reactions giving NADH
5
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
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
•
• Oxygenases transfer eand O2 to substrate
•
•
Fig. 19.11
VII Energy balance
Energy expenditure reflects oxygen consumption:
• Most O2 is used
by ATPases
[Cytochrome oxidase in
electron transport chain]
Peroxidases in peroxisome
Form H2O and S-OH
Hydroxylases
• (eg. Phe -> Tyr)
Fig. 19.12
Energy balance
Portion of food metabolized is related
to energy use:
• Basal metabolic rate
• Thermogenesis
• Physical activity
• Storage of excess
Fig. 19.14
“If you eat to much
and don’t exercise,
you will get fat”
(summarizes ATP-ADP cycle)
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