1. The Cellular Respiration
Lecture 12

2. Outline Cellular Respiration Overview Glycolysis
Citric Acid Cycle (Pyruvate Oxidation)
Oxidative Phosphorylation

3. Cellular Respiration - Overview
Life is work
Cellular respiration provides the energy for cells to do work

4. Photosynthesis in chloroplasts Cellular respiration in mitochondria
Light energy
Figure 9.2
ECOSYSTEM
Photosynthesis in chloroplasts
 O2
Organic molecules
CO2  H2O
Cellular respiration in mitochondria
Figure 9.2 Energy flow and chemical recycling in ecosystems.
ATP powers most cellular work
ATP
Heat energy

5. Cellular Respiration – Redox reactions
During cellular respiration – Glucose is oxidized and O2 is reduced
OIL RIG (or for biology, reduced – gains hydrogens; oxidized loses hydrogens)
becomes oxidized
becomes reduced

6. Cellular Respiration – Overview- NAD+
Electrons move away from Carbon atoms in Glucose to NAD+
NAD+ is a carrier molecule that transfer helps transfer energy from Glucose to make ATP
Oxidizing agent
(accepts electrons
and becomes reduced)
NAD+, hydride ion and a proton

7. Cellular Respiration – Overview- NADH
NADH then passes the electrons to the electron transport chain
The chain moves the electrons in a series of steps
O2 pulls the electrons down the chain
The energy yielded is used to regenerate ATP

8. Cellular Respiration – The stages
Three steps to get there:
Glycolysis
2 ATPs
Pyruvate Oxidation
Citric Acid (Kreb’s) Cycle – 2 ATPs
Oxidative phosphorylation
(Electron Transport Chain and Chemiosmosis) - 26 – 28 ATPs

9. Electrons carried via NADH Electrons carried via NADH and FADH2
Figure 9.6-3
Electrons carried via NADH
Electrons carried via NADH and FADH2
Oxidative phosphorylation: electron transport and chemiosmosis
Pyruvate oxidation
Glycolysis
Citric acid cycle
Glucose
Pyruvate
Acetyl CoA
CYTOSOL
MITOCHONDRION
Figure 9.6 An overview of cellular respiration.
ATP
ATP
ATP
Substrate-level phosphorylation
Substrate-level phosphorylation
Oxidative phosphorylation

10. Cellular Respiration – Step 1 - Glycolysis
Step one of cellular respiration - Oxidizing of glucose to pyruvate
Splitting of sugar
1 molecule of glucose is broken into two molecules of pyruvate
Occurs in the cytoplasm
Has two major phases
Energy investment phase
Energy payoff phase
Does not require O2

11. Energy Investment Phase
Glucose
2 ADP  2 P
2 ATP used
Energy Payoff Phase
4 ADP  4 P
4 ATP formed
2 NAD+  4 e  4 H+
2 NADH  2 H+
Figure 9.8
Figure 9.8 The energy input and output of glycolysis.
2 Pyruvate  2 H2O
Net
Glucose
2 Pyruvate  2 H2O
4 ATP formed  2 ATP used
2 ATP
2 NAD+  4 e  4 H+
2 NADH  2 H+

12. Glycolysis: Energy Investment Phase
Figure 9.9-1
Glycolysis: Energy Investment Phase
ATP
Glucose
Glucose 6-phosphate
ADP
Hexokinase 1
Figure 9.9 A closer look at glycolysis.

13. Phosphogluco- isomerase
Figure 9.9-2
Glycolysis: Energy Investment Phase
ATP
Glucose
Glucose 6-phosphate
Fructose 6-phosphate
ADP
Hexokinase
Phosphogluco- isomerase 1 2
Figure 9.9 A closer look at glycolysis.

14. Phosphogluco- isomerase Phospho- fructokinase
Figure 9.9-3
Glycolysis: Energy Investment Phase
ATP
ATP
Glucose
Glucose 6-phosphate
Fructose 6-phosphate
Fructose 1,6-bisphosphate
ADP
ADP
Hexokinase
Phosphogluco- isomerase
Phospho- fructokinase 1 2 3
Figure 9.9 A closer look at glycolysis.

15. Glycolysis: Energy Investment Phase
Figure 9.9-4
Glycolysis: Energy Investment Phase
ATP
ATP
Glucose
Glucose 6-phosphate
Fructose 6-phosphate
Fructose 1,6-bisphosphate
ADP
ADP
Hexokinase
Phosphogluco- isomerase
Phospho- fructokinase 1 2 3
Aldolase 4
Dihydroxyacetone phosphate
Glyceraldehyde 3-phosphate
Figure 9.9 A closer look at glycolysis.
To step 6
Isomerase 5

16. Triose phosphate dehydrogenase 1,3-Bisphospho- glycerate
Figure 9.9-5
Glycolysis: Energy Payoff Phase
2 NADH
2 NAD
+ 2 H
Triose phosphate dehydrogenase
2 P i
1,3-Bisphospho- glycerate 6
Figure 9.9 A closer look at glycolysis.

17. Glycolysis: Energy Payoff Phase
Figure 9.9-6
Glycolysis: Energy Payoff Phase
2 ATP
2 NADH
2 NAD
+ 2 H
2 ADP 2
Triose phosphate dehydrogenase
Phospho- glycerokinase
2 P i
1,3-Bisphospho- glycerate 7
3-Phospho- glycerate 6
Figure 9.9 A closer look at glycolysis.

18. Glycolysis: Energy Payoff Phase
Figure 9.9-7
Glycolysis: Energy Payoff Phase
2 ATP
2 NADH
2 NAD
+ 2 H
2 ADP 2 2
Triose phosphate dehydrogenase
Phospho- glycerokinase
Phospho- glyceromutase
2 P i
1,3-Bisphospho- glycerate 7
3-Phospho- glycerate 8
2-Phospho- glycerate 6
Figure 9.9 A closer look at glycolysis.

19. Glycolysis: Energy Payoff Phase
Figure 9.9-8
Glycolysis: Energy Payoff Phase
2 ATP
2 NADH
2 H2O
2 NAD
+ 2 H
2 ADP 2 2 2
Triose phosphate dehydrogenase
Phospho- glycerokinase
Phospho- glyceromutase
Enolase
2 P i 9
1,3-Bisphospho- glycerate 7
3-Phospho- glycerate 8
2-Phospho- glycerate
Phosphoenol- pyruvate (PEP) 6
Figure 9.9 A closer look at glycolysis.

20. Glycolysis: Energy Payoff Phase
Figure 9.9-9
Glycolysis: Energy Payoff Phase
2 ATP
2 ATP
2 NADH
2 H2O
2 ADP
2 NAD
+ 2 H
2 ADP 2 2 2
Triose phosphate dehydrogenase
Phospho- glycerokinase
Phospho- glyceromutase
Enolase
Pyruvate kinase
2 P i 9
1,3-Bisphospho- glycerate 7
3-Phospho- glycerate 8
2-Phospho- glycerate
Phosphoenol- pyruvate (PEP) 10
Pyruvate 6
Figure 9.9 A closer look at glycolysis.

21. Cellular Respiration – Step 2 – Citric Acid Cycle
Pyruvate enters mitochondrion
O2 dependent
Oxidation of glucose is completed

22. Cellular Respiration – Step 2 – Citric Acid Cycle - Pyruvate Oxidation
Pyruvate must be converted to Coenzyme A (acetyl CoA)
This links glycolysis to the citric acid cycle
Carried out by a multienzyme complex
Complex catalyses three reactions

23. MITOCHONDRION CYTOSOL CO2 Coenzyme A NAD NADH + H Acetyl CoA
Figure 9.10
MITOCHONDRION
CYTOSOL
CO2
Coenzyme A 1 3 2
NAD
NADH
+ H
Acetyl CoA
Figure 9.10 Oxidation of pyruvate to acetyl CoA, the step before the citric acid cycle.
Pyruvate
Transport protein

24. Cellular Respiration – Step 2 - Pyruvate Oxidation – the Citric Acid Cycle
Also called Krebs cycle
Completes the breakdown of pyruvate to CO2
Generates 1 ATP, 3 NADH, and 1 FADH2

25. Pyruvate CO2 NAD CoA NADH + H Acetyl CoA CoA CoA Citric acid cycle
Figure 9.11
CoA
CoA
Citric acid cycle
2 CO2
Figure 9.11 An overview of pyruvate oxidation and the citric acid cycle.
FADH2
3 NAD
FAD
3 NADH
+ 3 H
ADP + P i
ATP

26. Cellular Respiration – Step 2 - Pyruvate Oxidation – the Citric Acid Cycle
8 steps
Each step catalyzed by a specific enzyme
Acetyl group of acetyl CoA combines with oxaloacetate to form citrate
Next 7 steps decompose citrate back to oxaloacetate
Cycle
NADH and FADH2 relay electrons to the electron transport chain

27. Citric acid cycle Acetyl CoA Oxaloacetate Citrate Figure 9.12-1
CoA-SH 1
Figure
Oxaloacetate
Citrate
Citric acid cycle
Figure 9.12 A closer look at the citric acid cycle.

28. Citric acid cycle Acetyl CoA Oxaloacetate Citrate Isocitrate
CoA-SH 1
H2O
Figure
Oxaloacetate 2
Citrate
Isocitrate
Citric acid cycle
Figure 9.12 A closer look at the citric acid cycle.

29. Citric acid cycle Acetyl CoA Oxaloacetate Citrate Isocitrate
CoA-SH 1
H2O
Figure
Oxaloacetate 2
Citrate
Isocitrate
NAD
Citric acid cycle
NADH 3
+ H
CO2
-Ketoglutarate
Figure 9.12 A closer look at the citric acid cycle.

30. Citric acid cycle Acetyl CoA Oxaloacetate Citrate Isocitrate
CoA-SH 1
H2O
Figure
Oxaloacetate 2
Citrate
Isocitrate
NAD
Citric acid cycle
NADH 3
+ H
CO2
CoA-SH
-Ketoglutarate 4
Figure 9.12 A closer look at the citric acid cycle.
CO2
NAD
NADH
Succinyl CoA
+ H

31. Citric acid cycle Acetyl CoA Oxaloacetate Citrate Isocitrate
CoA-SH 1
H2O
Figure
Oxaloacetate 2
Citrate
Isocitrate
NAD
Citric acid cycle
NADH 3
+ H
CO2
CoA-SH
-Ketoglutarate 4
Figure 9.12 A closer look at the citric acid cycle.
CoA-SH 5
CO2
NAD
Succinate
P i
NADH
GTP
GDP
Succinyl CoA
+ H
ADP
ATP

32. Citric acid cycle Acetyl CoA Oxaloacetate Citrate Isocitrate
CoA-SH 1
H2O
Figure
Oxaloacetate 2
Citrate
Isocitrate
NAD
Citric acid cycle
NADH 3
+ H
CO2
Fumarate
CoA-SH
-Ketoglutarate 4
Figure 9.12 A closer look at the citric acid cycle. 6
CoA-SH 5
FADH2
CO2
NAD
FAD
Succinate
P i
NADH
GTP
GDP
Succinyl CoA
+ H
ADP
ATP

33. Citric acid cycle Acetyl CoA Oxaloacetate Malate Citrate Isocitrate
CoA-SH 1
H2O
Figure
Oxaloacetate 2
Malate
Citrate
Isocitrate
NAD
Citric acid cycle
NADH 3 7
+ H
H2O
CO2
Fumarate
CoA-SH
-Ketoglutarate 4
Figure 9.12 A closer look at the citric acid cycle. 6
CoA-SH 5
FADH2
CO2
NAD
FAD
Succinate
P i
NADH
GTP
GDP
Succinyl CoA
+ H
ADP
ATP

34. Citric acid cycle Acetyl CoA Oxaloacetate Malate Citrate Isocitrate
CoA-SH
NADH 1
H2O
+ H
Figure
NAD
Oxaloacetate 8 2
Malate
Citrate
Isocitrate
NAD
Citric acid cycle
NADH 3 7
+ H
H2O
CO2
Fumarate
CoA-SH
-Ketoglutarate 4
Figure 9.12 A closer look at the citric acid cycle. 6
CoA-SH 5
FADH2
CO2
NAD
FAD
Succinate
P i
NADH
GTP
GDP
Succinyl CoA
+ H
ADP
ATP

35. Cellular Respiration – Step 3 – Oxidative Phosphorylation
In oxidative phosphorylation chemiosmosis couples electron transport to ATP synthesis
NADH & FADH2 are electron carriers
They donate electrons to the electron transport chain
The electron transport chain powers ATP synthesis via oxidative phosphorylation

36. Cellular Respiration – Step 3 – Oxidative Phosphorylation – Electron transport chain
In the inner membrane (cristae) of the mitochondrion
Most components are membrane bound proteins
Most exist in complexes
The free energy of the electrons is dropping as they move down the chain
Each time they are moving to a more stable state
Ultimately they are passed to O2 to from H2O

37. Multiprotein complexes I 40 II
NADH 50
2 e
NAD
FADH2
2 e
FAD
Multiprotein complexes I 40
FMN II
FeS
FeS
Figure 9.13 Q
III
Cyt b 30
FeS
Cyt c1 IV
Free energy (G) relative to O2 (kcal/mol)
Cyt c
Cyt a
Cyt a3 20
Figure 9.13 Free-energy change during electron transport. 10
2 e
(originally from NADH or FADH2)
2 H + 1/2 O2
H2O

38. Cellular Respiration – Step 3 – Oxidative Phosphorylation – Electron transport chain
Electrons are transferred from NADH or FADH2 to the ETC
They are passed through several proteins
Cytochromes contain an iron atom
The ETC doesn’t generate ATP directly
It breaks the free-energy drop into smaller, manageable steps

39. Cellular Respiration – Step 3 – Oxidative Phosphorylation – ETC – Energy-coupling Mechanism
The transfer of electrons causes proteins to pump H+ from mitochondrial matrix to the intermembrane space
H+ moves back across the membrane
Movement drives ATP synthase
ATP synthase uses the exergonic flow of H+ to drive phosphorylation of ATP
Chemiosmosis – the use of a H+ gradient to drive cellular work

40. INTERMEMBRANE SPACE H Stator Rotor Internal rod Catalytic knob ADP +
Figure 9.14
Internal rod
Catalytic knob
Figure 9.14 ATP synthase, a molecular mill.
ADP +
P i
ATP
MITOCHONDRIAL MATRIX

41. Protein complex of electron carriersH H H
Protein complex of electron carriers
Figure 9.15 H
Cyt c IV Q
III I
ATP synth- ase II
2 H + 1/2O2
H2O
FADH2
FAD
Figure 9.15 Chemiosmosis couples the electron transport chain to ATP synthesis.
NAD
NADH
ADP  P i
ATP
(carrying electrons from food) H 1
Electron transport chain 2
Chemiosmosis
Oxidative phosphorylation

42. Cellular Respiration – Step 3 – Oxidative Phosphorylation – ETC – Energy-coupling Mechanism
Energy from the redox reaction of the ETC is stored in the proton (H+) gradient
Proton gradient is reffered to as a proton-motive force
The flow of protons back down the gradient provides the energy to drive ATP synthesis.

43. Cellular Respiration – Summary
Energy Flow:
glucose  NADH  electron transport chain  proton-motive force  ATP
~ 34% of the energy in a glucose molecule is transferred to ATP during cellular respiration
Makes about 32 ATP (not exactly known)

44. Oxidative phosphorylation: electron transport and chemiosmosis
Figure 9.16
Electron shuttles span membrane
MITOCHONDRION
2 NADH or
2 FADH2
2 NADH
2 NADH
6 NADH
2 FADH2
Oxidative phosphorylation: electron transport and chemiosmosis
Glycolysis
Pyruvate oxidation
Citric acid cycle
Glucose
2 Pyruvate
2 Acetyl CoA
Figure 9.16 ATP yield per molecule of glucose at each stage of cellular respiration.
 2 ATP
 2 ATP
 about 26 or 28 ATP
About 30 or 32 ATP
Maximum per glucose:
CYTOSOL

45. Cellular Respiration – Fermentation and anaerobic respiration
Allows cells to produce ATP without oxygen
The electron transport chain will not operate without O2
In instances of oxygen debt, glycolysis couples with fermentation or anaerobic respiration

46. Cellular Respiration – Fermentation
Fermentation uses substrate-level (direct transfer of phosphoryl group) phosphorylation instead of an electron transport chain to generate ATP
Consists of glycolysis plus reactions that regenerate NAD+
NAD+ can be reused by glycolysis
Two common types
Alcohol fermentation
Lactic acid fermentation

47. Cellular Respiration – Fermentation – alcohol fermentation
Pyruvate is converted to ethanol in 2 steps
First step releases CO2
Yeast – used in brewing, winemaking and baking

48.   2 ADP  2 P i 2 ATP Glucose Glycolysis 2 Pyruvate 2 NAD 2 NADH
Figure 9.17a
Glucose
Glycolysis
2 Pyruvate
2 NAD 
2 NADH
2 CO2 
2 H 
Figure 9.17 Fermentation.
2 Acetaldehyde
2 Ethanol
(a) Alcohol fermentation

49. Cellular Respiration – Fermentation – Lactic Acid
Pyruvate is reduced by NADH forming lactate
No CO2 is released
Lactic Acid fermentation by some fungi and bacteria is used to make yogurt and cheese
Human muscle cells use lactic acid fermentation to generate ATP during oxygen debt.

50.   2 ADP  2 P i 2 ATP Glucose Glycolysis 2 NAD 2 NADH  2 H
Figure 9.17b
Glucose
Glycolysis
2 NAD 
2 NADH 
2 H 
2 Pyruvate
Figure 9.17 Fermentation.
2 Lactate
(b) Lactic acid fermentation

51. Cellular Respiration – Anaerobic Respiration
Anaerobic respiration uses an electron transport chain with a different final electron acceptor
NO3-, SO42+, or CO32-

52. Cellular Respiration – Anaerobic Respiration
Obligate anaerobes – carry out fermentation or anaerobic respiration only
Cannot survive in the presence of O2
Facultative anaerobes – can survive with or without O2
Several types of yeast and bacteria

53. Cellular Respiration – Comparisons