1. 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

2. 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

3. 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

4. Glucose is universal fuel for every cell
Glycolysis is universal fuel:
1 glucose -> 2 pyruvate + 2 NADH + 2 ATP
Aerobic path:
Continued oxidation
Acetyl CoA -> TCA,
NADH, FAD(2H) -> 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

5. 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

6. 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

7. High energy phosphate bond of ATP: Strained phosphoanhydride bond
DG0’ kcal/mol standard conditions
Hydrolysis of ATP to ADP + Pi transfers PO4 to metabolic intermediate or protein, for next step
Fig. 19.2

8. Thermodynamics states what is possible:
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 ln[P]/[S]

9. Thermodynamics states what is possible:
Thermodynamics brief
Thermodynamics states what is possible:
Exergonic reactions give off energy (DG0’ < 0)
typically catabolic
Endergonic reactions require energy (DG0’ > 0)
typically anabolic
Unfavorable reactions are coupled to favorable reactions
Hydrolysis of ATP is very favorable
Additive DG0’ values determine overall direction

10. 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’ < 0)
Endergonic reactions require energy (DG0’ > 0)
Fig. 19.3

11. 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

12. Active transport: ATP hydrolysis moves molecules:
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

13. 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 -> glucose 6-P + H2O kcal/mol
ATP + H2O -> ADP + Pi kcal/mol
Sum: glucose + ATP -> glucose 6-P + ADP
Also Glucose -> G-1-P will be kcal/mol overall:
hydrolysis of ATP, through G-6-P to G-1-P

14. 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

15. 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 = favorable

16. 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

17. 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 -> H2O
ATP synthase makes ATP
lets in H+
Fig. 19.8

18. Oxidation: reduction reactions:
Electron donor gets oxidized; recipient is reduced
LEO GER:
Loss Electrons = oxidation; gain electrons is reduction
use coenzyme e- carriers
Fig NADH
Fig
FAD(2H)

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

20. 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

21. 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

22. 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 -> Tyr)
Fig

23. Energy expenditure reflects oxygen consumption: Most O2 is used
VII Energy balance
Energy expenditure reflects oxygen consumption:
Most O2 is used
by ATPases
Fig

24. Portion of food metabolized is related to energy use:
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 don’t exercise,
you will get fat”
(summarizes ATP-ADP cycle)