1. Glucose metabolism Some ATP Big bonus: NADH, FADH2 → REDUCING POWER
Glycolysis: 2 NADH, 2 ATP (net)
Pre-TCA cycle: 2 NADH
TCA cycle: 6 NADH, 2 FADH2, 2 A/GTP
Some ATP
Big bonus: NADH, FADH2 →
REDUCING POWER

2. Energy harvest by respiration
Carbon-carbon bonds: chemical energy
NADH, FADH2: energy of oxidation
Proton gradient: potential energy
ATP synthesis: useable chemical energy

3. Reducing power/ Energy of oxidation
Not very user-friendly
How to harvest the energy?
Electron transport chain
Change energy of oxidation into potential energy (H+ gradient)
Change potential energy into chemical energy
(F1Fo ATP synthase)

4. What is energy of oxidation?
Reducing potentials:
NAD+ + H+ + 2e- → NADH E'° ~ V
ubiquinone + 2H+ + 2e- → ubiquinol E'° ~
Electrons (e-) flow spontaneously from NADH to ubiquinone
NADH IS A STRONGER REDUCING AGENT THAN UBIQUINOL
ubiquinone
NADH
(oxidized form)
(reduced form)

5. Cataloging the red/ox reaction Transfer of e- from NADH to ubiquinone
E'° (V)
NADH → NAD+ + H+ + 2e-
+0.414
ubiquinone + 2H+ + 2e- → ubiquinol
+0.045
NADH + ubiquinone + H+ → ubiquinol + NAD+
+0.459
*extra energy*
not yet useable
DE'° > 0 ~ DG'° < 0

6. Electrons are passed among redox carriers
REDUCING STRENGTH
NADH→NAD+
FMN (↔FMNH2)
Fe-S Cluster
Ubiquinone (coenzyme Q)
Cytochrome C
Couple energetically favorable reactions
to energetically unfavorable reactions
Overall -DG
O2→H2O

7. Redox energy is transformed into potential energy
MATRIX
Generation of NADH
INTERMEMBRANE SPACE

8. INTERMEMBRANE SPACE MATRIX Flow of H+ into the matrix
Is energetically favorable
1. Input energy to
move H+ out
2. Harvest energy
INTERMEMBRANE SPACE
Low pH (higher [H+])
Electrically positive
MATRIX
High pH (lower [H+])
Electrically negative

9. Mitochondria actually look like the cartoons

10. Redox energy is transformed into potential energy
Establishment of a chemical and electric gradient
across the inner membrane
F1Fo ATP synthase
Transforms potential
Energy into useable
Chemical energy

11. Electron transport between electron carriers occurs in protein complexes within the inner membrane

12. Complex I NADH: Ubiquinone oxidoreductase 850kDa, 43 subunits
Converts NADH to NAD+
e- transferred through complex
FMN, Fe-S clusters
4 protons are ‘pumped’ from the matrix into the intermembrane space
Reduces ubiquinone (Q) to ubiquinol (QH2)

13. Ubiquinol (reduced coenzyme Q)

14. Complex III Coenzyme Q:cytochrome c oxidoreductase 250 kDa 11 subunits
2 coQ oxidized, one CytC reduced
e- carriers:
Hemes, Fe-S clusters
Net 4 H+ pumped to intermembrane space

15. Complex III, cont.

16. Cytochrome C Heme group carries electrons
Loosely associated with membrane
Shuttles e- from complex III to IV

17. Complex IV Cytochrome C oxidase 160 kDa 13 subunits Reduces oxygen
½ O2 + 2H+ + 2e- → H2O

18. Complex II (Use of FADH2)
Succinate dehydrogenase
Membrane-bound enzyme in the TCA cycle
140 kDa
4 subunits
FAD, Fe-S clusters carry electrons
e- transferred ubiquinone(Q)
QH2 carries e- to complex 3

19. Electron transport

20. Overall reaction starting with 2 e- from one NADH
NADH + H+ + ½ O2 → NAD+ + H2O
DG'° ~ -220 kJ/mol (of NADH)
-highly favorable
-coupled to transport of ~10 H+
against a chemical/electrical gradient

22. Oxidative phosphorylation
Involves reduction of O2 to H2O by NADH and FADH2
ATP synthesized through e- transfers
Inner mitochondrial membrane
Embedded protein complexes
Succinate dehydrogenase
Impermeable to most small molecules (and H+)
Creation of electrochemical gradients

23. ATP generation 2 NADH, 2 ATP from glycolysis (glucose)
1 NADH from pre-TCA (each pyruvate)
3 NADH, FADH2 from TCA (each acetyl CoA)
2 e- from NADH yields 2.5 ATP*
2 e- from FADH2  yields 1.5 ATP