1. Where did Bruce Lee get all that energy from?
Chapter 3
Cellular Respiration
Where did Bruce Lee get all that energy from?

2. 1 36 What is it? Cellular respiration O2
An aerobic process (requires oxygen)
Uses chemical energy from glucose to make ATP
Chemical energy is now stored in ATP for use throughout the body O2
glucose 1
ATP 36
Cellular resp.

3. Four Main Stages Glycolysis
Anaerobic
In cytosol
breaks glucose (6C) into 2 pyruvate molecules (3C)
releases ATP
Transition reaction (oxidative decarboxylation)
Pyruvate converted to acetyl CoA releasing CO2
Kreb’s Cycle
Within mitochondrial matrix
Oxidize each acetyl CoA to CO2
Releases ATP and co-enzymes (NADH, FADH2)
Electron Transport Chain
Along the inner mitochondrial membrane
Uses high energy electrons from NADH and FADH2 to create an electrochemical proton (H+) gradient which powers ATP synthesis

4. Fermentation
When oxygen is NOT available, cells can metabolize pyruvate (derived from glucose) by the process of fermentation.
Two Types
(i) alcohol fermentation: pyruvate (3C) converted
(reduced) to ethyl alcohol (2C) and CO2; occurs
in yeast cells
(ii) lactic acid fermentation: pyruvate(3C)
converted (reduced) to lactic acid (3C) in muscle cells

5. glucose + O2  CO2 + H2O + energy
Cellular Respiration
General Formula O2
glucose
CO2
H2O H+
Energy
glucose + O2  CO2 + H2O + energy
This process begins with glucose. Once it enters a cell, the process of glycolysis begins immediately in the cytoplasm where enzymes are waiting.

6. Glycolysis (I) Overview
This is the investment period of glycolysis
ATP is USED in order to “activate” glucose
This is accomplish by an enzyme mediated process called: substrate level phosphorylation
Involving the transfer of a phosphate group

7. Numbering the Carbons of Glucose
In order to keep track of how glucose is modified and rearranged during glycolysis we number each carbon C O 6 5
glucose 1 4 3 2

8. Glycolysis (I) glucose glucose-6-phosphate fructose-6-phosphate
fructose-1-6-bisphosphate
2 molecules of
PGAL (glyceraldehyde-3-phosphate) P P P C O C O P C O P P P C O P P C P C P

9. Glycolysis (I) glucose glucose-6-phosphate fructose-6-phosphate
ATP
glucose
glucose-6-phosphate
fructose-6-phosphate
fructose-1-6-biphosphate
2 molecules of
PGAL (glyceraldehyde-3-phosphate)
activation
ADP P C O
isomerization C O P
ATP
activation
ADP C O P P
cleavage C P C P

10. Investment Glycolysis (I)
1. Activation: Phosphate from ATP is added to glucose to form glucose-6-phosphate. [substrate-level phosphorylation]
2. Isomerization: Glucose-6-phosphate is rearranged to form fructose-6-phosphate.
3. Activation: A second phosphate from another ATP is added to form fructose-1,6-bisphosphate. [substrate-level phosphorylation]
4. Cleavage: The unstable fructose-1,6-bisphosphate splits into phosphoglyceraldehyde (PGAL) and dihydroxyacetone phosphate (DHAP).
Investment

11. Glycolysis (II) Overview
This is the pay-off period of glycolysis
ATP and NADH (a high energy molecule) are PRODUCED during glycolysis II
By the end of glycolysis II, glucose has been broken down from 6 carbons to a 3 carbon compound called Pyruvate (pyruvic acid)

12. Glycolysis (II) PGAL PGAP PGA PEP Pyruvate NAD NAD NADH NADH H2O H2O HPi Pi
NADH
NADH C P P P P P P C P P C P
H2O H
H2O H C P P P P P P C

13. isomerization / dehydration
Glycolysis (II)
PGAL
PGAP
PGA
PEP
Pyruvate C P C P
NADH
activation / redox
NADH C P P
ATP
ATP
dephosphorylation C P P
H2O H
isomerization / dehydration
H2O H C P C P
ATP
ATP
dephosphorylation P C

14. Pay-off Glycolysis (II)
5. Activation/Redox: Each molecule of PGAL is oxidized by NAD and gains a phosphate to form 1,3-bisphosphoglycerate (PGAP).
6. Phosphorylation: Each PGAP loses a phosphate to ADP resulting in 2 ATP and two 3-phosphoglycerate molecules (3-PGA).[substrate-level phosphorylation]
7. Isomerization: Both 3-PGA molecules are rearranged to form 2-phosphoglycerate (2-PGA).
[note: the text does not distinguish between 3-PGA and 2-PGA, but refers to both as PGA]
8. Dehydration: Both 2-PGA molecules are oxidized to phosphoenol pyruvate (PEP) by the removal of water.
9. Phosphorylation: Each PEP molecule loses a phosphate to ADP resulting in 2 more ATP and 2 molecules of pyruvate. [substrate-level phosphorylation]
Pay-off

15. 2 2 The Result Energy in Glycolysis Used 2 ATP Made 4 ATP Net Gain:
4ATP – 2ATP =
And 1 3 5
ATP 2 6 9
NADH 2
(high energy molecule)

16. Glycolysis: overall reaction
C6H12O6 + 2ADP + 2P + 2NAD+  2C3H4O3 + 2NADH + 2ATP
glucose (6C)
pyruvate (3C)
Notice: There is no oxygen used in glycolysis. It is an anaerobic process O2

17. The Power House!
In the cytosol, for each glucose molecule consumed, only 2 ATP were produced
This means that 34 more ATP are made in the mitochondria!
How do we get in there and what happens inside!?
nucleus
cytosol
ATP
ATP
mitochondria
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP
ATP

18. Inside the Mitochondria

19. Inside the Mitochondria
outer membrane: contains transport protein porin, which affects permeability
inner membrane: contains the phospholipid cardiolipin that makes membrane impermeable to ions, a condition which is required for ATP production
intermembrane space: fluid-filled area containing enzymes and hydrogen ions
matrix: location of Kreb’s Cycle
cristae: folds of the inner membrane where ETC enzymes are found

20. Transition Reaction C – C – C mitochondrion Intermembrane space
pyruvate
multi-enzyme pyruvate dehydrogenase complex

21. Transition Reaction 1. Decarboxylation CO2 C – C – C C – C
mitochondrion
Intermembrane space
1. Decarboxylation
CO2
C – C – C
pyruvate
C – C

22. Transition Reaction NAD+ NADH 2. Oxidation C – C C – C mitochondrion
Intermembrane space
NAD+
NADH
2. Oxidation
C – C
C – C

23. Transition Reaction C – C 3. Attachment mitochondrion
Intermembrane space
C – C
3. Attachment
CoA

24. Transition Reaction C – C 3. Attachment mitochondrion
Intermembrane space
Acetyl CoA
C – C
CoA
3. Attachment

25. Steps A and B together are referred to as oxidative decarboxylation
Transition Reaction
Decarboxylation (-CO2) of pyruvate leaving a 2C molecule
Oxidation by NAD+ forming an acetate molecule.
Attachment of coenzyme A forming acetyl coA.
Steps A and B together are referred to as oxidative decarboxylation

26. 1 1 Transition Reaction NADH
In the transition reaction, for each molecule of pyruvate:
CO2 1
is released
and
NADH 1
is produced

27. X2 2 1 Transition Reaction NADH NADH are released and are prodcued
Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose:
CO2 2
are released
and
NADH
are prodcued
CO2 1
is released
and
NADH
is produced X2

28. Krebs Cycle
1. Acetyl coA breaks into coenzyme A, which is recycled, and an acetyl group (2C) which joins to oxaloacetate (4C) forming citrate (6C).
2. Citrate (6C) converts to isocitrate (6C).
3. Isocitrate (6C) loses CO2 and is then oxidized by NAD forming alpha-ketoglutarate (5C). [oxidative decarboxylation]
4. Alpha-ketoglutarate (5C) is converted to succinyl-coA (4C) in 3 steps:
(i) loss of CO2
(ii) oxidation by NAD+
(iii) attachment of coenzyme A

29. Krebs Cycle
5. Succinyl coA (4C) is converted to succinate (4C) in the following way:
- coenzyme A breaks off and is recycled; phosphate attaches temporarily to succinate and is then transferred to GDP forming GTP; GTP transfers phosphate to ADP forming ATP (substrate level phosphorylation).
6. Succinate (4C) is oxidized by FAD to form fumarate (4C).
7. Water is added to fumarate (4C) to form malate (4C).
8. Malate (4C) is oxidized by NAD+ to form oxaloacetate, which is regenerated to begin the cycle again.

30. Krebs Cycle
Transition reaction
Krebs Cycle

31. Krebs Cycle
In the Krebs Cycle for each molecule of pyruvate:
CO2 2
are released
and
NADH 3
ATP 1
FADH2 1
are produced

32. X2 4 6 2 2 3 1 Krebs Cycle NADH FADH2 NADH FADH2
Remember: There are 2 pyruvates produced for each glucose. Therefore, for each glucose:
CO2 4
are released
NADH 6
and
FADH2 2
ATP
are produced
CO2 2
are released
NADH 3
and
FADH2 1
ATP
are prodcued X2

33. 1 2 6 The Story So Far C – C – C (6C) (3C) (1C) Tracking carbon:
glucose 1
C – C – C
pyruvate 2
CO2 6
(6C)
(3C)
(1C)

34. 2 2 2 6 4 10 2 The Story So Far Total Glycolysis
Tracking High Energy Molecules
Metabolic Process
ATP Produced
High Energy Molecules
Glycolysis
Transition Reaction (x2) (oxidative decarboxylation)
Krebs Cycle (x2)
Total
ATP 2
NADH
in cytosol
NADH 2
ATP 2
NADH 6
FADH2
ATP 4
NADH 10
FADH2 2

35. Using the High Energy Molecules
NADH and FADH2 have gained high energy electrons
These electrons are donated to electron carrier proteins in the Electron Transport Chain (ETC).
The energy from these electrons is then used to pump protons (H+) into the intermembrane space of the mitchondria

36. Electron Transport Chain
not part of the ETC C
Cristae Q
NADH
reductase
Co-enzyme Q
Cytochrome
b1c1
Cytochrome c
Cytochrome c
oxidase
ATP Synthase
Electron Carriers:
1. NADH reductase [protein]
2. Coenzyme Q [non-protein]
3. Cytochrome b1 c1
4. Cytochrome c
5. Cytochrome c oxidase
[protein]

37. Electron Transport Chain
Cristae Q
To pass electrons along ETC, each carrier is reduced (gains electrons) then oxidized (donates electrons)
Curious? Where do these electrons come from? Electrons come from hydrogen atoms (H atoms separate into electrons and protons)

38. Electron Transport Chain
Cristae Q
NAD+
NADH
NADH donates a pair of electrons to NADH reductase
electrons continue along ETC via sequential oxidations and reductions

39. Electron Transport Chain
Cristae Q
FADH2
FADH2 donates a pair of electrons to coenzyme Q
electrons also continue along ETC

40. Electron Transport Chain
Cristae Q
FADH2 donates a pair of electrons to coenzyme Q
electrons also continue along ETC

41. For each NADH, 6 H+ are pumped across the mitochondrion inner membrane
Cristae Q
NAD+ H+ H+ H+ H+ H+ H+ H+
NADH H+ H+ H+ H+ H+ H+
For each NADH, 6 H+ are pumped across the mitochondrion inner membrane

42. For each NADH, 6 H+ are pumped across the mitochondrion inner membrane
Cristae Q
H2O H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ O2
For each NADH, 6 H+ are pumped across the mitochondrion inner membrane
Oxygen is the final electron acceptor and is converted to H2O

43. H+ H+ H+ C
Cristae Q
H2O H+ H+ H+ H+ H+ H+ H+
FADH2 H+ H+ H+ H+ O2
For each FADH2, 4 H+ are pumped across the mitochondrion inner membrane

44. The electrochemical proton gradient
High Proton Concentration H+ H+
Gradient C
Cristae Q H+
Low Proton Concentration H+ H+ H+ H+ H+
The electrochemical proton gradient
(sometimes referred to as the proton motive force)

45. H+ H+ H+ H+ H+ H+ H+ C
Cristae Q
ATP H+ H+ H+ H+ H+ H+
Using the energy stored in the proton gradient, ATP is generated using oxidative phosphorylation: formation of ATP coupled to oxygen consumption
Using the electrochemial proton gradient to produce
ATP from ADP is called chemiosmosis

46. H+ H+ H+ H+ H+ H+ H+ C
Cristae Q
ATP
ATP
ATP H+ H+ H+ H+ H+ H+
1 ATP is generated for each proton pair flowing through ATP synthase.
Pumps H+ 6 3
NADH

47. H+ H+ H+ H+ H+ H+ H+ C
Cristae Q
ATP
ATP H+ H+ H+ H+ H+ H+
1 ATP is generated for each proton pair flowing through ATP synthase.
Pumps H+ 4 2
FADH2

48. ATP synthase works a bit like a water mill

49. The WHOLE process… Cristae C Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

50. The WHOLE process… Cristae NAD+ NADH C Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

51. The WHOLE process… Cristae C H2O O2 Q H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+

52. The WHOLE process… Cristae C ATP ATP ATP Q H+ H+ H+ H+ H+ H+ H+ H+ H+

53. The WHOLE process… Cristae C ATP ATP ATP Q H+ H+ H+ H+ H+ H+ H+ H+ H+

54. Remember: BEFORE the ETC we had…
Summing up ATP
Remember: BEFORE the ETC we had…
Metabolic Process
ATP Produced
High Energy Molecules
Glycolysis
Transition Reaction (x2) (oxidative decarboxylation)
Krebs Cycle (x2)
Total
ATP 2
NADH
in cytosol
NADH 2
ATP 2
NADH 6
FADH2
ATP 4
NADH 10
FADH2 2

55. In the Electron Transport Chain
Summing up ATP
In the Electron Transport Chain
Molecules from
High Energy Molecules
ATP produced in ETC
Glycolysis
Transition Reaction (x2) (oxidative decarboxylation)
Krebs Cycle (x2)
Total
NADH 2
ATP 4
in cytosol
NADH 2
ATP 6
NADH 6
FADH2 2
ATP 22 10
FADH2 2
ATP 32
NADH

56. 2 2 4 + From Glycolysis 2 2 6 6 2 22 10 2 34 32 Summing up ATP Total
IN TOTAL
Molecules from
High Energy Molecules
ATP produced in ETC
Glycolysis
Transition Reaction (x2) (oxidative decarboxylation)
Krebs Cycle (x2)
Total
ATP 2
NADH 2
ATP 4
in cytosol
From Glycolysis
ATP 2
NADH 2
ATP 6
NADH 6
FADH2 2
ATP 22 10
FADH2 2
ATP 34
ATP 32
NADH

57. 2 2 4 + From Krebs Cycle 2 2 6 6 2 22 2 10 2 36 34 Summing up ATP
IN TOTAL
Molecules from
High Energy Molecules
ATP produced in ETC
Glycolysis
Transition Reaction (x2) (oxidative decarboxylation)
Krebs Cycle (x2)
Total
ATP 2
NADH 2
ATP 4
in cytosol
From Krebs Cycle
ATP 2
NADH 2
ATP 6
NADH 6
FADH2 2
ATP 22
ATP 2 10
FADH2 2
ATP 36
ATP 34
NADH

58. glucose + oxygen carbon dioxide + water + energy
Overall Reaction
glucose 1
CO2 6
glucose
CO2
NAD+ 10
FAD 2
NADH 10
FADH2 2
NAD+ 10
FAD 2
Catalysts
ATP 36
Energy
H2O H+
H2O H+ O2 O2
glucose oxygen carbon dioxide + water + energy

59. glucose + oxygen carbon dioxide + water + energy
Overall Reaction
Phase (location)
Glycolysis (cytosol)
Transition Reaction (mito.)
Kreb’s Cycle (mito.)
ETC (mito.)
glucose 1
CO2 6
some
NAD+ 10
FAD 2
ATP 36
some
H2O H+ O2
glucose oxygen carbon dioxide + water + energy