1. Cellular Respiration: Harvesting Chemical Energy
Chapter 9
Cellular Respiration: Harvesting Chemical Energy

2. Life Is Work Living cells The giant panda
Require transfusions of energy from outside sources to perform many tasks
The giant panda
Obtains energy for its cells by eating plants

3. powers most cellular work
The energy stored in the organic molecules of food comes from the sun
Energy flows into an ecosystem as sunlight and leaves as heat
Light energy
ECOSYSTEM
CO2 + H2O
Photosynthesis in chloroplasts
Cellular respiration in mitochondria
Organic molecules
+ O2
ATP
powers most cellular work
Heat energy

4. Photosynthesis generates oxygen and organic molecules
Used by the mitochondria of eukaryotes as fuel for cellular respiration
Respiration breaks this fuel down generating ATP
The waste products (CO2 and water) are the raw material for photosynthesis

5. Catabolic pathways yield energy by oxidizing organic fuels
Organic componds store energy in their arrangment of atoms
With the help of enzymes a cell degrades complex organic molecules to more simple ones
metabolic pathway that release stored energy by breaking down complex molecules are called catabolic pathways
Example: fermentation (partial degradation of sugars that occurs without the use of oxygen)

6. Catabolic Pathways and Production of ATP
The breakdown of organic molecules is exergonic
Releases energy to the environment

7. Cellular respiration
Is the most prevalent and efficient catabolic pathway
Consumes oxygen and organic molecules such as glucose
Yields ATP
Mitochondria
Organic compounds + Oxygen → CO2 + Water + Energy

8. To keep working Cells must regenerate ATP From ADP and phosphate
To understand this we need to examine the fundamental chemical processes:
oxidation and reduction

9. Redox Reactions: Oxidation and Reduction
Catabolic pathways yield energy
Due to the transfer of electrons
The relocation of electrons releases energy stored in organic molecules
This energy is used to synthesize ATP

10. The Principle of Redox Redox reactions
Transfer electrons from one reactant to another by oxidation and reduction
This electron transfers are oxidation-reduction reactions or redox reactions
the loss of electrons from one substance is called oxidation
Addition of electrons to enother substance is called reduction
Notice: adding is called reduction. Negatively charged electrons added to an atom reduce the amount of positive charge of that atom.

11. Example of redox reaction: Na is electron donor or reducing agent
Cl is electron acceptor or oxidizing agent
Na Cl Na Cl–
becomes oxidized (gives electron)
becomes reduced (accepts electron)

12. Do not completely exchange electrons
Some redox reactions
Do not completely exchange electrons
Some of them change the degree of electron sharing in covalent bonds
Oxygen is one of the most potent of all oxidizing agents
CH4 H C O
Methane (reducing agent)
Oxygen (oxidizing agent)
Carbon dioxide
Water +
2O2
CO2
Energy
2 H2O
becomes oxidized
becomes reduced
Reactants
Products
Figure 9.3

13. Oxidation of Organic Fuel Molecules During Cellular Respiration
Glucose is oxidized and oxygen is reduced
The electrons lose potential energy along the way and energy is released
Hydrogen is transferred from glucose to oxygen
By oxidizing glucose, respiration liberates stored energy from glucose and makes it available for ATP synthesis
C6H12O6 + 6O CO2 + 6H2O + Energy
becomes oxidized
becomes reduced

14. Stepwise Energy Harvest via NAD+ and the Electron Transport Chain
Cellular respiration
Oxidizes glucose in a series of steps
Each step catalyzed by an enzyme
At key steps electrons are stripped from the glucose
The hydrogen atoms are not directly trasferred to oxygen but are usually transferred to a coenzyme NAD+ (nicotinamide adenine dinucleotide)
Derivative of the vitamin niacin
Functions as oxidizing agent during respiration (electron acceptor)

15. Electrons from organic compounds
Are usually first transferred to NAD+, a coenzyme
NAD+ H O O– P
CH2 HO OH N+ C
NH2 N
Nicotinamide (oxidized form) +
2[H]
(from food)
Dehydrogenase
Reduction of NAD+
Oxidation of NADH
2 e– + 2 H+
2 e– + H+
NADH
Nicotinamide (reduced form)
Figure 9.4

16. NADH, the reduced form of NAD+
Passes the electrons to the electron transport chain
NADH recieved hydrogen in the reaction
Each NADH molecule formed during respiration represents stored energy that can be tapped to make ATP

17. (a) Uncontrolled reaction
If electron transfer is not stepwise
A large release of energy occurs
As in the reaction of hydrogen and oxygen to form water
(a) Uncontrolled reaction
Free energy, G
H2O
Explosive release of heat and light energy
Figure 9.5 A
H2 + 1/2 O2

18. The electron transport chain
Passes electrons in a series of steps instead of in one explosive reaction
Uses the energy from the electron transfer to form ATP
Consists of number of molecules built into the inner membrane of a mitochondrion

19. The Stages of Cellular Respiration: A short preview
Respiration is a cumulative function of three metabolic stages
Glycolysis
The citric acid cycle
Oxidative phosphorylation

20. Oxidative phosphorylation: electron transport and chemiosmosis
An overview of cellular respiration
Figure 9.6
Electrons
carried
via NADH
Glycolsis
Glucose
Pyruvate
ATP
Substrate-level
phosphorylation
Electrons carried
via NADH and
FADH2
Citric acid cycle
Oxidative phosphorylation: electron transport and chemiosmosis
Oxidative
Mitochondrion
Cytosol

21. Glycolysis The citric acid cycle
Breaks down glucose into two molecules of pyruvate
Occurs in cytosol
The citric acid cycle
Completes the breakdown of glucose by oxidizing a derivative of pyruvate to CO2
Takes place in mitochondrial matrix

22. Some steps in glycolysis and citric acid cycle are redox reactions
Dehydrogenase enzymes trasfer electrons from substrates to NAD+ forming NADH

23. Oxidative phosphorylation as third step in respiration
Is driven by the electron transport chain
Generates ATP
Powered by the redox reactions of the electron transport chain

24. Both glycolysis and the citric acid cycle
Can generate ATP by substrate-level phosphorylation
This mode of ATP synthesis occurs when an enzyme transfers a phosphate group from a substrate to ADP as in oxidative phosphorylation
Substrate molecule refers to an organic molecule generated during the catabolism of glucose
Figure 9.7
Enzyme
ATP
ADP
Product
Substrate P +

25. Glycolysis harvests energy by oxidizing glucose to pyruvate
Means “splitting of sugar”
Breaks down glucose into pyruvate
Occurs in the cytoplasm of the cell

26. Energy investment phase
Glycolysis consists of two major phases
Energy investment phase
Energy payoff phase
Glycolysis
Citric acid cycle
Oxidative phosphorylation
ATP
2 ATP
4 ATP
used
formed
Glucose
2 ATP + 2 P
4 ADP + 4
2 NAD+ + 4 e- + 4 H +
2 NADH
+ 2 H+
2 Pyruvate + 2 H2O
Energy investment phase
Energy payoff phase
4 ATP formed – 2 ATP used
2 NAD+ + 4 e– + 4 H +
Figure 9.8

27. A closer look at the energy investment phase
Dihydroxyacetone
phosphate
Glyceraldehyde-
3-phosphate H OH HO
CH2OH O P
CH2O
CH2 C
CHOH
ATP
ADP
Hexokinase
Glucose
Glucose-6-phosphate
Fructose-6-phosphate
Phosphoglucoisomerase
Phosphofructokinase
Fructose-
1, 6-bisphosphate
Aldolase
Isomerase
Glycolysis 1 2 3 4 5
Oxidative
phosphorylation
Citric
acid
cycle
Figure 9.9 A

28. 1, 3-Bisphosphoglycerate
A closer look at the energy payoff phase
2 NAD+
NADH 2
+ 2 H+
Triose phosphate
dehydrogenase
P i P C
CHOH O
CH2 O–
1, 3-Bisphosphoglycerate
2 ADP
2 ATP
Phosphoglycerokinase
3-Phosphoglycerate
Phosphoglyceromutase
CH2OH H
2-Phosphoglycerate
2 H2O
Enolase
Phosphoenolpyruvate
Pyruvate kinase
CH3 6 8 7 9 10
Pyruvate
Figure 9.8 B
Final product of glycolysis

29. completes the energy-yielding oxidation of organic molecules
The citric acid cycle
completes the energy-yielding oxidation of organic molecules
The citric acid cycle
Takes place in the matrix of the mitochondrion

30. Before the citric acid cycle can begin
Pyruvate must first be converted to acetyl CoA, which links the cycle to glycolysis
CYTOSOL
MITOCHONDRION
NADH
+ H+
NAD+ 2 3 1
CO2
Coenzyme A
Pyruvate
Acetyle CoA S
CoA C
CH3 O
Transport protein O–
Figure 9.10

31. Oxidative phosphorylation
An overview of the citric acid cycle
ATP
2 CO2
3 NAD+
3 NADH
+ 3 H+
ADP + P i
FAD
FADH2
Citric acid cycle
CoA
Acetyle CoA
NADH
CO2
Pyruvate (from glycolysis, 2 molecules per glucose)
Glycolysis
Oxidative phosphorylation
Figure 9.11

32. A closer look at the citric acid cycle
Acetyl CoA
NADH
Oxaloacetate
Citrate
Malate
Fumarate
Succinate
Succinyl
CoA
a-Ketoglutarate
Isocitrate
Citric
acid
cycle S SH
FADH2
FAD
GTP
GDP
NAD+
ADP
P i
CO2
H2O
+ H+ C
CH3 O
COO–
CH2 HO HC CH 1 2 3 4 5 6 7 8
Glycolysis
Oxidative
phosphorylation
ATP
Figure 9.12
Figure 9.12

33. Summary!
Cellular respiration
Redox reactions
Glycolysis
Citric acid cycle

34. Oxidative phosphorylation
During it, chemiosmosis couples electron transport to ATP synthesis
NADH and FADH2
Donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation

35. The Pathway of Electron Transport
In the electron transport chain
Electrons from NADH and FADH2 lose energy in several steps
Most components of the chain are proteins which exist in multiprotein complexes I to IV
Includes also prosthetic groups
Non-protein components essential for the catalytic functions of certain enzymes

36. At the end of the chain Electrons are passed to oxygen, forming water
H2O O2
NADH
FADH2
FMN
Fe•S O
FAD
Cyt b
Cyt c1
Cyt c
Cyt a
Cyt a3
2 H + + 12 I II
III IV
Multiprotein complexes 10 20 30 40 50
Free energy (G) relative to O2 (kcl/mol)
Figure 9.13

37. Generally, the electron transport chain makes no ATP directly
Makes fall of electrons from food to oxygen easier, breaking a large free-energy drop into a series of smaller steps that release energy in manageable amounts
How? → Chemiosmosis

38. Chemiosmosis: The Energy-Coupling Mechanism
ATP synthase
Is the enzyme that actually makes ATP from ADP and inorganic phosphate
Located at the inner membrane of the mitochondrion
Works like an ion pump running in reverse
Uses the energy of an existing ion gradient to power ATP synthesis
It is proton gradient (hydrogen)
The process in which the energy is stored and used to drive cellular work is called chemiosmosis

39. In general terms:
Chemiosmosis is an energy-coupling mechanism that uses energy stored in the form of an H+ gradient across a membrane to drive cellular work

40. At certain steps along the electron transport chain
Electron transfer causes protein complexes to pump H+ from the mitochondrial matrix to the intermembrane space
The resulting H+ gradient
Stores energy
Drives chemiosmosis in ATP synthase
Is referred to as a proton-motive force

41. Chemiosmosis and the electron transport chain
Oxidative
phosphorylation.
electron transport
and chemiosmosis
Glycolysis
ATP
Inner
Mitochondrial
membrane H+
P i
Protein complex
of electron
carners
Cyt c I II
III IV
(Carrying electrons
from, food)
NADH+
FADH2
NAD+
FAD+
2 H+ + 1/2 O2
H2O
ADP +
Electron transport chain
Electron transport and pumping of protons (H+),
which create an H+ gradient across the membrane
Chemiosmosis
ATP synthesis powered by the flow
Of H+ back across the membrane
synthase Q
Oxidative phosphorylation
Intermembrane
space
mitochondrial
matrix
Figure 9.15

42. An Accounting of ATP Production by Cellular Respiration
During respiration, most energy flows in this sequence
Glucose → NADH → electron transport chain → proton-motive force → ATP
But how many ATPs can be generated?

43. There are three main processes in this metabolic enterprise
Electron shuttles
span membrane
CYTOSOL
2 NADH
2 FADH2
6 NADH
Glycolysis
Glucose 2
Pyruvate
Acetyl
CoA
Citric
acid
cycle
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
MITOCHONDRION
by substrate-level
phosphorylation
by oxidative phosphorylation, depending
on which shuttle transports electrons
from NADH in cytosol
Maximum per glucose:
About
36 or 38 ATP
+ 2 ATP
+ about 32 or 34 ATP or
Figure 9.16

44. About 40% of the energy in a glucose molecule
Is transferred to ATP during cellular respiration, making approximately 38 ATP
This number however cannot be fixed
Mostly because some of the reactions are not directly coupled

45. enables some cells to produce ATP without the use of oxygen
Fermentation
enables some cells to produce ATP without the use of oxygen
Why? Oxidation is the loss of electrons to any electron acceptor not only oxygen
Cellular respiration
Relies on oxygen to produce ATP
In the absence of oxygen
Cells can still produce ATP through fermentation

46. Glycolysis
Can produce ATP with or without oxygen, in aerobic or anaerobic conditions
Couples with fermentation to produce ATP

47. Fermentation consists of
Types of Fermentation
Fermentation consists of
Glycolysis plus reactions that regenerate NAD+
can be reused to oxidize sugar by glyocolysis
Two types of fermentation:
1. alcohol fermentation
2. lactic acid fermentation

48. (a) Alcohol fermentation
In alcohol fermentation
Pyruvate is converted to ethanol (ethyl alcohol) in two steps
The first step releases CO2 from the pyruvate which is converted to the two-carbon compound acetaldehyde
In the second step acetaldehyde is reduced by NADH to ethanol
This regenerates the supply of NAD+ needed for the continuation of glycolysis
2 ADP + 2 P1
2 ATP
Glycolysis
Glucose
2 NAD+
2 NADH
2 Pyruvate
2 Acetaldehyde
2 Ethanol
(a) Alcohol fermentation H OH
CH3 C
O – O
CO2 2

49. (b) Lactic acid fermentation
During lactic acid fermentation
Pyruvate is reduced directly to NADH to form lactate as a waste product
No release of CO2
This fermentation by certain fungi and bacteria is used in the dairy industry to make cheese and other milk products
2 ADP + 2 P1
2 ATP
Glycolysis
Glucose
2 NAD+
2 NADH
2 Lactate
(b) Lactic acid fermentation O– C O
CH3 OH H

50. Fermentation and Cellular Respiration Compared
Both fermentation and cellular respiration
Use glycolysis to oxidize glucose and other organic fuels to pyruvate
Net production of 2 molecules of ATP by substrate-level phosphorylation
NAD+ is the oxidizing agent that accepts electrons from food during glycolysis

51. The key difference is the contrasting mechanism for oxidizing NADH back to NAD+
In fermentation the final electron acceptor is an organic molecule such as pyruvate (lactic acid fermentation) or acetaldehyde (alcohol fermentation)
In respiration the final electron acceptor is oxygen which also produces more ATP

52. Pyruvate is a key juncture in catabolism
Glucose
CYTOSOL
Pyruvate
No O2 present
Fermentation
O2 present
Cellular respiration
Ethanol or
lactate
Acetyl CoA
MITOCHONDRION
Citric
acid
cycle
Figure 9.18

53. The Evolutionary Significance of Glycolysis
Occurs in nearly all organisms
Probably evolved in ancient prokaryotes before there was oxygen in the atmosphere
Early organisms produced ATP exclusively from glycolysis which does not require oxygen

54. Glycolysis and the citric acid cycle connect to many other metabolic pathways
Can be catabolic or anabolic pathways

55. The Versatility of Catabolism
Catabolic pathways
Funnel electrons from many kinds of organic molecules into cellular respiration
To make ATP
Glycolysis can accept a wide range of carbohydrates for catabolism
Starch, glycogen (polysaccharides), proteins and fats

56. Most of the energy of a fat is stored in the fatty acids
Beta oxidation breaks fatty acids down to two-carbon fragments
Those enter the citric acid cycle as acetyl CoA
Fats are great fuels
1 gram of fat oxidized by respiration produces more than twice as much ATP as a gram of carbohydrates

57. The catabolism of various molecules from food
Amino
acids
Sugars
Glycerol
Fatty
Glycolysis
Glucose
Glyceraldehyde-3- P
Pyruvate
Acetyl CoA
NH3
Citric
acid
cycle
Oxidative
phosphorylation
Fats
Proteins
Carbohydrates
Figure 9.19

58. Biosynthesis (Anabolic Pathways)
The body
Uses small molecules to build other substances
These small molecules
May come directly from food or through glycolysis or the citric acid cycle
Can be diverted into anabolic pathways as precursors for other molecules

59. Regulation of Cellular Respiration via Feedback Mechanisms
Is controlled by allosteric enzymes at key points in glycolysis and the citric acid cycle
Feedback inhibition: the end product of the anabolic pathway inhibits the enzyme that catalyzes an early step of the pathway
Example: phosphofructokinase which catalyzes 3rd step in glycolysis

60. Allosteric enzyme
Inhibited by ATP and stimulated by AMP
As ATP accumulates, inhibition of the enzyme slows down glycolysis
Active again upon conversion of ATP to ADP (and AMP)

61. Summary!
Oxidative phosphorylation
Electron transport chain
Chemiosmosis
Fermentations
Allosteric enzymes