1. Ch 9 – Cellular Respiration: Harvesting Chemical Energy
Living cells require energy from outside sources
Energy flows into an ecosystem as sunlight and leaves as heat
Photosynthesis generates O2 and organic molecules, which are used in cellular respiration
Cells use chemical energy stored in organic molecules to regenerate ATP, which powers work
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2. Organic molecules Cellular respiration in mitochondria
Fig. 9-2
Light
energy
ECOSYSTEM
Photosynthesis
in chloroplasts
Organic
molecules
CO2 + H2O
+ O2
Cellular respiration
in mitochondria
Figure 9.2 Energy flow and chemical recycling in ecosystems
ATP
ATP powers most cellular work
Heat
energy

3. 9.1: Catabolic pathways yield energy by oxidizing organic fuels
The breakdown of organic molecules is exergonic (releases energy)
Fermentation is a partial degradation of sugars that occurs without O2 (anaerobic)
Aerobic respiration consumes organic molecules and O2 and yields ATP
Anaerobic respiration is similar to aerobic respiration but consumes compounds other than O2
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4. C6H12O6 + 6 O2  6 CO2 + 6 H2O + Energy (ATP + heat)
Cellular respiration includes both aerobic and anaerobic processes but is often used to refer to aerobic respiration
Although carbohydrates, fats, and proteins are all consumed as fuel, it is helpful to trace cellular respiration with the sugar glucose:
C6H12O6 + 6 O2  6 CO2 + 6 H2O + Energy (ATP + heat)
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5. 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
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6. The Principle of Redox
Reactions that transfer electrons are called oxidation-reduction or redox reactions
In oxidation, a substance loses electrons, or is oxidized (LEO: Loss of Electrons = Oxidation)
The electron donor = the “reducing agent”
In reduction, a substance gains electrons, or is reduced (GER: Gain of Electrons = Reduction)
The electron acceptor = the “oxidizing agent”
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7. Na is the reducing agent; it becomes oxidized as it loses / donates its electron to Cl
(loses electron)
becomes reduced
(gains electron)
Cl is the oxidizing agent; it becomes reduced as it receives / accepts the electron from Na

8. In this redox reaction, electrons are not transferred but there has been a change in electron sharing in covalent bonds.
Reactants
Products
becomes oxidized
becomes reduced
Figure 9.3 Methane combustion as an energy-yielding redox reaction
Methane
(reducing
agent)
Oxygen
(oxidizing
agent)
Carbon dioxide
Water
Loses electrons
Accepts electrons

9. During cellular respiration, the fuel (such as glucose) is oxidized, and O2 is reduced:
becomes oxidized
becomes reduced

10. 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
Dehydrogenase
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

11. NADH H+ NAD+ + 2[H] + H+ 2 e– + 2 H+ 2 e– + H+ Dehydrogenase
Fig. 9-4
2 e– + 2 H+
2 e– + H+
NADH H+
Dehydrogenase
Reduction of NAD+
NAD+ +
2[H] + H+
Oxidation of NADH
Nicotinamide
(reduced form)
Nicotinamide
(oxidized form)
Figure 9.4 NAD+ as an electron shuttle

12. NADH passes the electrons to the electron transport chain (ETC)
The ETC passes electrons in a series of steps, instead of one explosive reaction
O2 pulls electrons down the chain in an energy-yielding tumble
In aerobic respiration, O2 is the final electron acceptor in the ETC
The energy yielded is used to regenerate ATP
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13. (a) Uncontrolled reaction (b) Cellular respiration
Fig. 9-5
H2 + 1/2 O2
2 H +
1/2 O2
(from food via NADH)
Controlled
release of
energy for
synthesis of
ATP
2 H e–
ATP
Explosive
release of
heat and light
energy
ATP
Electron transport
chain
Free energy, G
Free energy, G
ATP
2 e–
Figure 9.5 An introduction to electron transport chains
1/2 O2
2 H+
H2O
H2O
(a) Uncontrolled reaction
(b) Cellular respiration

14. 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)
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15. Electrons carried via NADH ATP Substrate-level phosphorylation
Fig
Electrons
carried
via NADH
Glycolysis
Glucose
Pyruvate
Cytosol
Figure 9.6 An overview of cellular respiration
ATP
Substrate-level
phosphorylation

16. Electrons carried via NADH Electrons carried via NADH and FADH2
Fig
Electrons
carried
via NADH
Electrons carried
via NADH and
FADH2
Glycolysis
Citric
acid
cycle
Glucose
Pyruvate
Mitochondrion
Cytosol
Figure 9.6 An overview of cellular respiration
ATP
ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation

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

18. BioFlix: Cellular Respiration
The process that generates most of the ATP is called oxidative phosphorylation because it is powered by redox reactions
Oxidative phosphorylation accounts for almost 90% of the ATP generated by cellular respiration
A smaller amount of ATP is formed in glycolysis and the citric acid cycle by substrate-level phosphorylation
BioFlix: Cellular Respiration
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19. Enzyme Enzyme ADP P Substrate + ATP Product
Figure 9.7 Substrate-level phosphorylation
Product

20. Glycolysis occurs in the cytoplasm and has two major phases:
9.2: Glycolysis harvests chemical energy by oxidizing glucose to pyruvate
Glycolysis (“splitting of sugar”) breaks down glucose (6C) into two molecules of pyruvate (3C each) -- animation
Glycolysis occurs in the cytoplasm and has two major phases:
Energy investment phase (put in 2 ATP)
Energy payoff phase (make 4 ATP)
Net gain of 2 ATP
Also produces 2 NADH (electron carrier)

21. Energy investment phase
Fig. 9-8
Energy investment phase
Glucose
2 ADP + 2 P
2 ATP
used
Energy payoff phase
4 ADP + 4 P
4 ATP
formed
2 NAD e– + 4 H+
2 NADH
+ 2 H+
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 e– + 4 H+
2 NADH + 2 H+

22. Glycolysis occurs in the cytoplasm.
Site of Respiration
Glycolysis occurs in the cytoplasm.
The rest of aerobic respiration occurs in the mitochondrion
The Krebs / Citric Acid cycle occurs in the mitochondrial matrix
The ETC occurs in the mitochondrial membrane (cristae)
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23. Mitochondria: Chemical Energy Conversion
Mitochondria are in nearly all eukaryotic cells
They have a smooth outer membrane and an inner membrane folded into cristae
The inner membrane creates two compartments: intermembrane space and mitochondrial matrix
Cristae present a large surface area for enzymes that synthesize ATP
Structure / function! Surface area!

24. in the mitochondrial matrix
Fig. 6-17
Intermembrane space
Outer membrane
Free ribosomes
in the mitochondrial matrix
Inner membrane
Cristae
Matrix
0.1 µm

25. In the presence of O2, pyruvate enters the mitochondrion
9.3: The citric acid cycle completes the energy-yielding oxidation of organic molecules
In the presence of O2, pyruvate enters the mitochondrion
Before the citric acid cycle can begin, pyruvate must be converted to acetyl CoA
Prior to this, one C from pyruvate is removed as CO2
CoA = coenzyme A (organic substance that helps enzymes function)
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26. CYTOSOL MITOCHONDRION NAD+ NADH + H+ 2 1 3 Acetyl CoA Pyruvate
Fig. 9-10
CYTOSOL
MITOCHONDRION
NAD+
NADH
+ H+ 2 1 3
Acetyl CoA
Figure 9.10 Conversion of pyruvate to acetyl CoA, the junction between glycolysis and the citric acid cycle
Pyruvate
Coenzyme A
CO2
Transport protein

27. The citric acid cycle, also called the Krebs cycle, takes place within the mitochondrial matrix
The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per turn
Remember, the Krebs cycle turns 2x for each glucose molecule broken down by glycolysis
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28. The remaining 2C compound joins with CoA to form acetyl CoA
Fig. 9-11
Pyruvate
1C leaves as CO2
CO2
NAD+
CoA
The remaining 2C compound joins with CoA to form acetyl CoA
NADH
+ H+
Acetyl CoA
CoA
CoA is removed and the acetyl group enters the Krebs cycle
CoA
The acetyl group combines with oxaloacetate to form citrate
Oxaloacetate is regenerated for the next round
Citric
acid
cycle
2 CO2 are produced / released 2
CO2
Figure 9.11 An overview of the citric acid cycle
FADH2
3 NAD+
FAD 3
NADH
1 FADH2 is produced
+ 3 H+
3 NADH are produced
ADP + P i
ATP
1 ATP is produced

29. How the Krebs Cycle Works (animation)
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
The NADH and FADH2 produced by the cycle relay electrons extracted from food to the ETC
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30. 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
For the Cell Biology Video ATP Synthase 3D Structure — Side View, go to Animation and Video Files.
For the Cell Biology Video ATP Synthase 3D Structure — Top View, go to Animation and Video Files.
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31. 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 between 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 H2O – that energy is harnessed to make ATP
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32. Fig. 9-13
Notice that electrons from NADH and FADH2 enter the ETC at different points; this is because the electrons in NADH have more energy than the electrons in FADH2
NADH 50 2 e–
NAD+
FADH2 2 e–
FAD
Multiprotein
complexes  40
FMN
FAD
Fe•S 
Fe•S Q

Cyt b
Fe•S 30
Cyt c1 IV
Free energy (G) relative to O2 (kcal/mol)
Cyt c
Cyt a
Cyt a3 20
Oxygen is the final electron acceptor; when the electrons combine with oxygen, water is produced / released.
Figure 9.13 Free-energy change during electron transport 10 2 e–
(from NADH
or FADH2)
2 H+ + 1/2 O2
H2O

33. The electron transport chain generates no ATP in and of itself
Electrons from NADH and FADH2 are passed through a number of proteins, including cytochromes, to O2
The electron transport chain generates no ATP in and of itself
The chain’s function is to break the large free-energy drop from food to O2 into smaller steps, releasing energy in manageable amounts
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34. 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
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35. Fig. 9-14
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
INTERMEMBRANE SPACE
Protons diffuse back into the mitochondrial matrix through ATP synthase
This causes a conformational change in the ATP synthase molecule, catalyzing the formation of ATP
Animation H+
Stator
Rotor
Internal
rod
Figure 9.14 ATP synthase, a molecular mill
Cata-
lytic
knob
ADP + P
ATP i
MITOCHONDRIAL MATRIX

36. Intermembrane space Mitochondrial matrix Fig. 9-16 H+ H+ H+ H+
Protein complex
of electron
carriers
Cyt c V Q
 
ATP synthase 
2 H+ + 1/2O2
H2O
FADH2
FAD
NADH
NAD+
Figure 9.16 Chemiosmosis couples the electron transport chain to ATP synthesis
ADP + P
ATP i
(carrying electrons
from food) H+ 1
Electron transport chain 2
Chemiosmosis
Oxidative phosphorylation
Mitochondrial matrix

37. Cellular Respiration Summary
Fig. 9-17
Cellular Respiration Summary
CYTOSOL
Electron shuttles
span membrane
MITOCHONDRION
2 NADH or
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
Figure 9.17 ATP yield per molecule of glucose at each stage of cellular respiration
About
36 or 38 ATP
Maximum per glucose:

38. Most cellular respiration requires O2 to produce ATP
9.5: Fermentation and anaerobic respiration enable cells to produce ATP without the use of oxygen
Most 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 or anaerobic respiration to produce ATP
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39. Anaerobic respiration uses an electron transport chain with an electron acceptor other than O2; for example, sulfate
Fermentation uses phosphorylation instead of an electron transport chain to generate ATP
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40. Two common types are alcohol fermentation and lactic acid fermentation
Types of Fermentation
Fermentation starts with glycolysis and continues with reactions that regenerate NAD+, which can be reused by glycolysis
Two common types are alcohol fermentation and lactic acid fermentation
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41. Animation: Fermentation Overview
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
Animation: Fermentation Overview
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42. (a) Alcohol fermentation
Fig. 9-18a
2 ADP + 2 P
2 ATP i
Glucose
Glycolysis
2 Pyruvate
2 NAD+
2 NADH 2
CO2
+ 2 H+
Figure 9.18a Fermentation
2 Acetaldehyde
2 Ethanol
(a) Alcohol fermentation

43. 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
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44. (b) Lactic acid fermentation
Fig. 9-18b
2 ADP + 2 P
2 ATP i
Glucose
Glycolysis
2 NAD+
2 NADH
+ 2 H+
2 Pyruvate
Figure 9.18b Fermentation
2 Lactate
(b) Lactic acid fermentation

45. Fermentation and Aerobic 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 or acetaldehyde) in fermentation and O2 in cellular respiration
Cellular respiration produces 38 ATP per glucose molecule; fermentation produces 2 ATP per glucose molecule
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46. Obligate anaerobes carry out fermentation or anaerobic respiration and cannot survive in the presence of O2
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
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47. Ethanol or lactate Citric acid cycle
Fig. 9-19
Glucose
Glycolysis
CYTOSOL
Pyruvate
O2 present:
Aerobic cellular
respiration
No O2 present:
Fermentation
MITOCHONDRION
Ethanol or
lactate
Acetyl CoA
Figure 9.19 Pyruvate as a key juncture in catabolism
Citric
acid
cycle

48. The Evolutionary Significance of Glycolysis
Glycolysis occurs in nearly all organisms
Glycolysis probably evolved in ancient prokaryotes before there was oxygen in the atmosphere
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49. Glycolysis accepts a wide range of carbohydrates
9.6: Glycolysis and the citric acid cycle connect to many other metabolic pathways
Catabolic pathways are versatile; they funnel electrons from many kinds of organic molecules (not just glucose!) into cellular respiration
Glycolysis accepts a wide range of carbohydrates
Proteins must first be digested to amino acids; amino groups can feed glycolysis or the citric acid cycle
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50. Fatty acids are broken down by beta oxidation and yield acetyl CoA
Fats are digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA)
Fatty acids are broken down by beta oxidation and yield acetyl CoA
An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate
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51. Citric acid cycle Oxidative phosphorylation
Fig. 9-20
Proteins
Carbohydrates
Fats
Amino
acids
Sugars
Glycerol
Fatty
acids
Glycolysis
Glucose
Glyceraldehyde-3- P
NH3
Pyruvate
Acetyl CoA
Figure 9.20 The catabolism of various molecules from food
Citric
acid
cycle
Oxidative
phosphorylation

52. 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
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53. 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
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54. Figure 9.21 The control of cellular respiration
Glucose
AMP
Glycolysis
Fructose-6-phosphate
Stimulates +
Phosphofructokinase – –
Fructose-1,6-bisphosphate
Inhibits
Inhibits
Pyruvate
ATP
Citrate
Acetyl CoA
Figure 9.21 The control of cellular respiration
Citric
acid
cycle
Oxidative
phosphorylation