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

2. Overview: Life Is Work
Living cells require energy from outside sources
Some animals, such as the giant panda, obtain energy by eating plants; others feed on organisms that eat plants

4. Energy flows into an ecosystem as sunlight and leaves as heat
Photosynthesis generates oxygen and organic molecules, which are used in cellular respiration
Cells use chemical energy stored in organic molecules to regenerate ATP, which powers work

5. LE 9-2 Light energy ECOSYSTEM Photosynthesis in chloroplasts CO2 + H2O
Organic
molecules
+ O2
Cellular respiration
in mitochondria
ATP
powers most cellular work
Heat
energy

6. Concept 9.1: Catabolic pathways yield energy by oxidizing organic fuels
Several processes are central to cellular respiration and related pathways

7. Catabolic Pathways and Production of ATP
The breakdown of organic molecules is exergonic
Fermentation is a partial degradation of sugars that occurs without oxygen
Cellular respiration consumes oxygen and organic molecules and yields ATP
Although carbohydrates, fats, and proteins are all consumed as fuel, it is helpful to trace cellular respiration with the sugar glucose:
C6H12O6 + 6O2  6CO2 + 6H2O + Energy (ATP + heat)

8. Redox Reactions: Oxidation and Reduction
The transfer of electrons during chemical reactions releases energy stored in organic molecules
This released energy is ultimately used to synthesize ATP

9. The Principle of Redox
Chemical reactions that transfer electrons between reactants are called oxidation-reduction reactions, or redox reactions
In oxidation, a substance loses electrons, or is oxidized
In reduction, a substance gains electrons, or is reduced (the amount of positive charge is reduced)
Xe Y X Ye-
becomes oxidized (loses electron)
becomes reduced (gains electron)

10. The electron donor is called the reducing agent
The electron receptor is called the oxidizing agent

11. Some redox reactions do not transfer electrons but change the electron sharing in covalent bonds
An example is the reaction between methane and oxygen

12. Methane (reducing agent) Oxygen (oxidizing agent) Carbon dioxide Water
LE 9-3
Reactants
Products
becomes oxidized
CH4 +
2 O2
CO2 +
Energy +
2 H2O
becomes reduced H H C H O O O C O H O H H
Methane
(reducing
agent)
Oxygen
(oxidizing
agent)
Carbon dioxide
Water

13. Oxidation of Organic Fuel Molecules During Cellular Respiration
During cellular respiration, the fuel (such as glucose) is oxidized and oxygen is reduced:
C6H12O6 + 6O CO2 + 6H2O + Energy
becomes oxidized
becomes reduced

14. Stepwise Energy Harvest via NAD+ and the Electron Transport Chain
In cellular respiration, glucose and other organic molecules are broken down in a series of steps
Electrons from organic compounds are usually first transferred to NAD+, a coenzyme
As an electron acceptor, NAD+ functions as an oxidizing agent during cellular respiration
Each NADH (the reduced form of NAD+) represents stored energy that is tapped to synthesize ATP

15. LE 9-4 NADH NAD+ 2 e– + 2 H+ 2 e– + H+ H+ Dehydrogenase + 2[H] + H+
(from food) + H+
Nicotinamide
(reduced form)
Nicotinamide
(oxidized form)

16. NADH passes the electrons to the electron transport chain
Unlike an uncontrolled reaction, the electron transport chain passes electrons in a series of steps instead of one explosive reaction
Oxygen pulls electrons down the chain in an energy-yielding tumble
The energy yielded is used to regenerate ATP

17. Electron transport chain+
1/2 O2
2 H +
1/2 O2
(from food via NADH)
Controlled
release of
energy for
synthesis of
ATP
2 H+ + 2 e–
ATP
Explosive
release of
heat and light
energy
ATP
Free energy, G
Free energy, G
Electron transport chain
ATP
2 e–
1/2 O2
2 H+
H2O
H2O
Uncontrolled reaction
Cellular respiration

18. The Stages of Cellular Respiration: A Preview
Cellular respiration has three stages:
Glycolysis (breaks down glucose into two molecules of pyruvate)
The citric acid cycle (completes the breakdown of glucose)
Oxidative phosphorylation (accounts for most of the ATP synthesis)
The process that generates most of the ATP is called oxidative phosphorylation because it is powered by redox reactions
[Animation listed on slide following figure]

19. LE 9-6_1 Glycolysis Glucose Pyruvate Cytosol Mitochondrion ATP
Substrate-level
phosphorylation

20. LE 9-6_2 Glycolysis Citric acid cycle Glucose Pyruvate Cytosol
Mitochondrion
ATP
ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation

21. LE 9-6_3 Electrons carried via NADH Electrons carried via NADH and
FADH2
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
Glycolysis
Citric
acid
cycle
Glucose
Pyruvate
Cytosol
Mitochondrion
ATP
ATP
ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation
Oxidative
phosphorylation

22. Animation: Cell Respiration Overview

23. Oxidative phosphorylation accounts for almost 90% of the ATP generated by cellular respiration
A small amount of ATP is formed in glycolysis and the citric acid cycle by substrate-level phosphorylation

24. LE 9-7
Enzyme
Enzyme
ADP P
Substrate +
ATP
Product

25. Animation: Glycolysis
Concept 9.2: Glycolysis harvests energy by oxidizing glucose to pyruvate
Glycolysis (“splitting of sugar”) breaks down glucose into two molecules of pyruvate
Glycolysis occurs in the cytoplasm and has two major phases:
Energy investment phase
Energy payoff phase
Animation: Glycolysis

26. LE 9-8 Energy investment phase Glucose 2 ADP + 2 P 2 ATP used
Glycolysis
Citric
acid
cycle
Oxidative
phosphorylation
Energy payoff phase
ATP
ATP
ATP
4 ADP + 4 P
4 ATP
formed
2 NAD+ + 4 e– + 4 H+
2 NADH
+ 2 H+
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+

27. LE 9-9a_1 Glucose ATP Hexokinase ADP Glucose-6-phosphate Glycolysis
Citric
acid
cycle
phosphorylation
Oxidation
Glucose
ATP
ATP
ATP
ATP
Hexokinase
ADP
Glucose-6-phosphate

28. LE 9-9a_2 Glucose ATP Hexokinase ADP Glucose-6-phosphate
Glycolysis
Citric
acid
cycle
Oxidation
phosphorylation
Glucose
ATP
ATP
ATP
ATP
Hexokinase
ADP
Glucose-6-phosphate
Phosphoglucoisomerase
Fructose-6-phosphate
ATP
Phosphofructokinase
ADP
Fructose-
1, 6-bisphosphate
Aldolase
Isomerase
Dihydroxyacetone
phosphate
Glyceraldehyde-
3-phosphate

29. LE 9-9b_1 2 NAD+ Triose phosphate dehydrogenase 2 NADH + 2 H+
1, 3-Bisphosphoglycerate
2 ADP
Phosphoglycerokinase
2 ATP
3-Phosphoglycerate
Phosphoglyceromutase
2-Phosphoglycerate

30. LE 9-9b_2 2 NAD+ Triose phosphate dehydrogenase 2 NADH + 2 H+
1, 3-Bisphosphoglycerate
2 ADP
Phosphoglycerokinase
2 ATP
3-Phosphoglycerate
Phosphoglyceromutase
2-Phosphoglycerate
Enolase
2 H2O
Phosphoenolpyruvate
2 ADP
Pyruvate kinase
2 ATP
Pyruvate

31. Concept 9.3: The citric acid cycle completes the energy-yielding oxidation of organic molecules
Before the citric acid cycle can begin, pyruvate must be converted to acetyl CoA, which links the cycle to glycolysis

32. LE 9-10
CYTOSOL
MITOCHONDRION
NAD+
NADH
+ H+
Acetyl Co A
Pyruvate
CO2
Coenzyme A
Transport protein

33. Animation: Electron Transport
The citric acid cycle, also called the Krebs cycle, takes place within the mitochondrial matrix
The cycle oxidizes organic fuel derived from pyruvate, generating one ATP, 3 NADH, and 1 FADH2 per turn
Animation: Electron Transport

34. LE 9-11 Pyruvate (from glycolysis, 2 molecules per glucose) CO2 NAD+
Citric
acid
cycle
Oxidation
phosphorylation
NAD+
CoA
NADH
ATP
ATP
ATP
+ H+
Acetyl CoA
CoA
CoA
Citric
acid
cycle 2
CO2
FADH2
3 NAD+
FAD 3
NADH
+ 3 H+
ADP + P i
ATP

35. The citric acid cycle has eight steps, each catalyzed by a specific enzyme
The acetyl group of acetyl CoA joins the cycle by combining with oxaloacetate, forming citrate
The next seven steps decompose the citrate back to oxaloacetate, making the process a cycle
The NADH and FADH2 produced by the cycle relay electrons extracted from food to the electron transport chain

36. LE 9-12_1 Acetyl CoA H2O Oxaloacetate Citrate Isocitrate Citric acid
Glycolysis
Citric
acid
cycle
Oxidation
phosphorylation
ATP
ATP
ATP
Acetyl CoA
H2O
Oxaloacetate
Citrate
Isocitrate
Citric
acid
cycle

37. LE 9-12_2 Acetyl CoA H2O Oxaloacetate Citrate Isocitrate CO2 Citric
Glycolysis
Citric
acid
cycle
Oxidation
phosphorylation
ATP
ATP
ATP
Acetyl CoA
H2O
Oxaloacetate
Citrate
Isocitrate
CO2
Citric
acid
cycle
NAD+
NADH
+ H+
a-Ketoglutarate
CO2
NAD+
NADH
Succinyl
CoA
+ H+

38. LE 9-12_3 Acetyl CoA H2O Oxaloacetate Citrate Isocitrate CO2 Citric
Glycolysis
Citric
acid
cycle
Oxidation
phosphorylation
ATP
ATP
ATP
Acetyl CoA
H2O
Oxaloacetate
Citrate
Isocitrate
CO2
Citric
acid
cycle
NAD+
NADH
Fumarate
+ H+
a-Ketoglutarate
FADH2
CO2
NAD+
FAD
Succinate P
NADH i
GTP
GDP
Succinyl
CoA
+ H+
ADP
ATP

39. LE 9-12_4 Acetyl CoA NADH + H+ H2O NAD+ Oxaloacetate Malate Citrate
Glycolysis
Citric
acid
cycle
Oxidation
phosphorylation
ATP
ATP
ATP
Acetyl CoA
NADH
+ H+
H2O
NAD+
Oxaloacetate
Malate
Citrate
Isocitrate
CO2
Citric
acid
cycle
NAD+
H2O
NADH
Fumarate
+ H+
a-Ketoglutarate
FADH2
CO2
NAD+
FAD
Succinate P
NADH i
GTP
GDP
Succinyl
CoA
+ H+
ADP
ATP

40. Concept 9.4: During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis
Following glycolysis and the citric acid cycle, NADH and FADH2 account for most of the energy extracted from food
These two electron carriers donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation

41. The Pathway of Electron Transport
The electron transport chain is in the cristae of the mitochondrion
Most of the chain’s components are proteins, which exist in multiprotein complexes
The carriers alternate reduced and oxidized states as they accept and donate electrons
Electrons drop in free energy as they go down the chain and are finally passed to O2, forming water

42. LE 9-13 NADH 50 FADH2 Multiprotein complexes 40 I FMN FAD Fe•S Fe•S IIQ
III
Cyt b
Oxidative
phosphorylation:
electron transport
and chemiosmosis
Glycolysis
Citric
acid
cycle
Fe•S 30
Cyt c1
Free energy (G) relative to O2 (kcal/mol) IV
Cyt c
Cyt a
ATP
ATP
ATP
Cyt a3 20 10
2 H+ + 1/2 O2
H2O

43. The electron transport chain generates no ATP
The chain’s function is to break the large free- energy drop from food to O2 into smaller steps that release energy in manageable amounts

44. Chemiosmosis: The Energy-Coupling Mechanism
Electron transfer in the electron transport chain causes proteins to pump H+ from the mitochondrial matrix to the intermembrane space
H+ then moves back across the membrane, passing through channels in ATP synthase
ATP synthase uses the exergonic flow of H+ to drive phosphorylation of ATP
This is an example of chemiosmosis, the use of energy in a H+ gradient to drive cellular work

45. LE 9-14 INTERMEMBRANE SPACE H+
A rotor within the membrane spins as shown when H+ flows past
it down the H+ gradient. H+ H+ H+ H+ H+ H+
A stator anchored in the membrane holds the knob stationary.
A rod (or “stalk”) extending into the knob also spins, activating catalytic sites in the knob. H+
Three catalytic sites in the stationary knob join inorganic phosphate to ADP to make ATP.
ADP +
ATP P i
MITOCHONDRAL MATRIX

46. Animation: Fermentation Overview
The energy stored in a H+ gradient across a membrane couples the redox reactions of the electron transport chain to ATP synthesis
The H+ gradient is referred to as a proton-motive force, emphasizing its capacity to do work
Animation: Fermentation Overview

47. LE 9-15 Inner mitochondrial membrane H+ H+ H+ H+ Protein complex
Citric
acid
cycle
Oxidative
phosphorylation:
electron transport
and chemiosmosis
Glycolysis
ATP
ATP
ATP H+ H+ H+ H+
Protein complex
of electron
carriers
Cyt c
Intermembrane
space Q IV I
III
ATP
synthase
Inner
mitochondrial
membrane II
2H+ + 1/2 O2
H2O
FADH2
FAD
NADH
+ H+
NAD+
ADP + P
ATP i
(carrying electrons
from food) H+
Mitochondrial
matrix
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
Oxidative phosphorylation

48. An Accounting of ATP Production by Cellular Respiration
During cellular respiration, most energy flows in this sequence:
glucose NADH electron transport chain proton-motive force ATP
About 40% of the energy in a glucose molecule is transferred to ATP during cellular respiration, making about 38 ATP

49. LE 9-16 CYTOSOL Electron shuttles span membrane MITOCHONDRION 2 NADHor
2 FADH2
2 NADH
2 NADH
6 NADH
2 FADH2
Glycolysis
Oxidative
phosphorylation:
electron transport
and
chemiosmosis 2
Pyruvate 2
Acetyl
CoA
Citric
acid
cycle
Glucose
+ 2 ATP
+ 2 ATP
+ about 32 or 34 ATP
by substrate-level
phosphorylation
by substrate-level
phosphorylation
by oxidation phosphorylation, depending
on which shuttle transports electrons
form NADH in cytosol
About
36 or 38 ATP
Maximum per glucose:

50. Concept 9.5: Fermentation enables some cells to produce ATP without the use of oxygen
Cellular respiration requires O2 to produce ATP
Glycolysis can produce ATP with or without O2 (in aerobic or anaerobic conditions)
In the absence of O2, glycolysis couples with fermentation to produce ATP

51. Types of Fermentation
Fermentation consists of glycolysis plus reactions that regenerate NAD+, which can be reused by glycolysis
Two common types are alcohol fermentation and lactic acid fermentation

52. In alcohol fermentation, pyruvate is converted to ethanol in two steps, with the first releasing CO2
Alcohol fermentation by yeast is used in brewing, winemaking, and baking
Play

53. Alcohol fermentation 2 ADP + 2 P 2 ATP Glucose Glycolysis 2 Pyruvate
LE 9-17a
2 ADP + 2 P
2 ATP i
Glucose
Glycolysis
2 Pyruvate
2 NAD+
2 NADH 2
CO2
+ 2 H+
2 Acetaldehyde
2 Ethanol
Alcohol fermentation

54. In lactic acid fermentation, pyruvate is reduced to NADH, forming lactate as an end product, with no release of CO2
Lactic acid fermentation by some fungi and bacteria is used to make cheese and yogurt
Human muscle cells use lactic acid fermentation to generate ATP when O2 is scarce

55. Lactic acid fermentation
LE 9-17b
2 ADP + 2 P
2 ATP i
Glucose
Glycolysis
2 NAD+
2 NADH 2
CO2
+ 2 H+
2 Pyruvate
2 Lactate
Lactic acid fermentation

56. Fermentation and Cellular Respiration Compared
Both processes use glycolysis to oxidize glucose and other organic fuels to pyruvate
The processes have different final electron acceptors: an organic molecule (such as pyruvate) in fermentation and O2 in cellular respiration
Cellular respiration produces much more ATP

57. Yeast and many bacteria are facultative anaerobes, meaning that they can survive using either fermentation or cellular respiration
In a facultative anaerobe, pyruvate is a fork in the metabolic road that leads to two alternative catabolic routes

58. LE 9-18
Glucose
CYTOSOL
Pyruvate
No O2 present
Fermentation
O2 present
Cellular respiration
MITOCHONDRION
Ethanol or
lactate
Acetyl CoA
Citric
acid
cycle

59. The Evolutionary Significance of Glycolysis
Glycolysis occurs in nearly all organisms
Glycolysis probably evolved in ancient prokaryotes before there was oxygen in the atmosphere

60. Concept 9.6: Glycolysis and the citric acid cycle connect to many other metabolic pathways
Gycolysis and the citric acid cycle are major intersections to various catabolic and anabolic pathways

61. The Versatility of Catabolism
Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration
Glycolysis accepts a wide range of carbohydrates
Proteins must be digested to amino acids; amino groups can feed glycolysis or the citric acid cycle
Fats are digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA)
An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate

62. LE 9-19 Carbohydrates Fats Amino acids Sugars Glycerol Fatty acids
Proteins
Carbohydrates
Fats
Amino
acids
Sugars
Glycerol
Fatty
acids
Glycolysis
Glucose
Glyceraldehyde-3- P
NH3
Pyruvate
Acetyl CoA
Citric
acid
cycle
Oxidative
phosphorylation

63. Biosynthesis (Anabolic Pathways)
The body uses small molecules to build other substances
These small molecules may come directly from food, from glycolysis, or from the citric acid cycle

64. Regulation of Cellular Respiration via Feedback Mechanisms
Feedback inhibition is the most common mechanism for control
If ATP concentration begins to drop, respiration speeds up; when there is plenty of ATP, respiration slows down
Control of catabolism is based mainly on regulating the activity of enzymes at strategic points in the catabolic pathway

65. Fructose-1,6-bisphosphate
LE 9-20
Glucose
AMP
Glycolysis
Fructose-6-phosphate
Stimulates +
Phosphofructokinase – –
Fructose-1,6-bisphosphate
Inhibits
Inhibits
Pyruvate
ATP
Citrate
Acetyl CoA
Citric
acid
cycle
Oxidative
phosphorylation