1. It all reduces down to water.
The Electron Transport Chain and Oxidative Phosphorylation Prof. S. Kajuna
It all reduces down to water.

2. Mitochondria outer membrane relatively permeable
inner membrane permeable only to those things with specific transporters
Impermeable to NADH and FADH2
Permeable to pyruvate
Compartmentalization
Kreb's and β-oxidation in matrix
Glycolysis in cytosol

3. Most energy from Redox
electrons during metabolic reactions sent to NAD and FAD
Glycolysis
In cytosol
produces 2 NADH
Pyruvate dehydrogenase reaction
In mitochondrial matrix
2 NADH / glucose
Krebs
6 NADH and 2 FADH2 / glucose

4. Electron Transport Chain
Groups of redox proteins
On inner mitochondrial membrane
Binding sites for NADH and FADH2
On matrix side of membrane
Electrons transferred to redox proteins
NADH reoxidized to NAD+
FADH2 reoxidized to FAD

5. 4 Complexes proteins in specific order
Transfers 2 electrons in specific order
Proteins localized in complexes
Embedded in membrane
Ease of electron transfer
Electrons ultimately reduce oxygen to water
2 H+ + 2 e- + ½ O2 -- H2O

6. Electron Transport Chain

7. Complex 1 Has NADH binding site NADH reductase activity
NADH - NAD+
NADH ---> FMN--->FeS---> ubiquinone
ubiquinone ---> ubiquinone H2
4 H+ pumped/NADH

8. Electron Transport Chain

9. Complex II succinate ---FAD—ubiquinone Contains coenzyme Q
FADH2 binding site
FAD reductase activity
FADH2 -- FAD

10. Electron Transport Chain

11. Complex III ubiquinone - ubiquinone ox while cyt C gets reduced
Also contains cytochromes b
proton pump 4H+
Adds to gradient
8 H+ / NADH
4 H+ / FADH2

12. Electron Transport Chain

13. Complex IV reduction of oxygen cytochrome oxidase
cyt a+a3 red ---> oxidized state
oxygen ---> water
2 H+ + 2 e- + ½ O2 -- 2 H2O
transfers e- one at a time to oxygen
Pumps 2H+ out
Total of 10 H+ / NADH
Total of 6 H+ / FADH2

14. Totals
Proton gradient created as electrons transferred to oxygen forming water
10 H+ / NADH
6 H+ / FADH2

15. Electron Transport Chain

16. Generation of ATP Proton dependant ATP synthetase
Uses proton gradient to make ATP
Protons pumped through channel on enzyme
From intermembrane space into matrix
~4 H+ / ATP
Called chemiosmotic theory

17. Totals
NADH
10 H+ X 1 ATP = 2.5 ATP
4 H+
FADH2
6 H+ X 1 ATP = 1.5 ATP

18. Total ATP from mitochondrial matrix
Pyruvate dehydrogenase
NADH ……………………………….2.5 ATP
Krebs
3 NADH X 2.5 ATP/NADH ……….7.5 ATP
FADH2 X 1.5 ATP / FADH2……….1.5 ATP
GTP X 1 ATP / GTP ……………..1.0 ATP
(from a separate reaction)
Total …………….12.5 ATP
(Per glucose = X 2 = 25 ATP)

19. What about NADH from glycolysis?
NADH made in cytosol
Can’t get into matrix of mitochondrion
2 mechanisms
In muscle and brain
Glycerol phosphate shuttle
In liver and heart
Malate / aspartate shuttle

20. Glycerol Phosphate shuttle

21. Glycerol phosphate shuttle
In muscle and brain
Each NADH converted to FADH2 inside mitochondrion
FADH2 enters later in the electron transport chain
Produces 1.5 ATP

22. Total ATP per glucose in muscle and brain
Gycerol phosphate shuttle
2 NADH per glucose - 2 FADH2
2 FADH2 X 1.5 ATP / FADH2……….3.0 ATP
2 ATP in glycoysis ……………………2.0 ATP
From pyruvate and Krebs
12.5 ATP X 2 per glucose …………… ATP
Total = ATP/ glucose

23. Malate – Aspartate Shuttle

24. Malate – Aspartate Shuttle in cytosol
In liver and heart
NADH oxidized while reducing oxaloacetate to malate
Malate dehydrogenase
Malate crosses membrane

25. Malate – Aspartate Shuttle in matrix
Malate reoxidized to oxaloacetate
Malate dehydrogenase
NAD+ reduced to NADH
NADH via electron transport yields 2.5 ATP
Mlate – Aspartate Shuttle in cytosol

26. Total ATP per glucose in liver and heart
Malate – Aspartate Shuttle
2 NADH per glucose - 2 NADH
2 NADH X 2.5 ATP / NADH…………5.0 ATP
2 ATP from glycolysis………………..2.0 ATP
From pyruvate and Krebs
12.5 ATP X 2 per glucose …………… ATP
Total = ATP/ glucose

27. Summary Total ATP / glucose Muscle and brain 30.0 ATP
Uses glycerol phosphate shuttle
Heart and liver ATP
Uses malate aspartate shuttle