1. In the presence of O2, pyruvate enters the mitochondrion
Concept 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, which links the cycle to glycolysis
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2. 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

3. 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
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4. Pyruvate CO2 NAD+ CoA NADH + H+ Acetyl CoA CoA CoA Citric acid cycle 2
Fig. 9-11
Pyruvate
CO2
NAD+
CoA
NADH
+ H+
Acetyl CoA
CoA
CoA
Citric
acid
cycle 2
CO2
Figure 9.11 An overview of the citric acid cycle
FADH2
3 NAD+
FAD 3
NADH
+ 3 H+
ADP + P i
ATP

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

7. 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
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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8. 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 H2O
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9. Figure 9.13 Free-energy change during electron transport
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
Figure 9.13 Free-energy change during electron transport e– 10 2
(from NADH
or FADH2)
2 H+ + 1/2 O2
H2O

10. The electron transport chain generates no ATP
Electrons are transferred from NADH or FADH2 to the electron transport chain
Electrons are passed through a number of proteins including cytochromes (each with an iron atom) to O2
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
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11. 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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12. INTERMEMBRANE SPACE H+ Stator Rotor Internal rod Cata- lytic knob ADP
Fig. 9-14
INTERMEMBRANE SPACE H+
Stator
Rotor
Internal
rod
Figure 9.14 ATP synthase, a molecular mill
Cata-
lytic
knob
ADP + P
ATP i
MITOCHONDRIAL MATRIX

13. Number of photons detected (103)
Fig. 9-15
EXPERIMENT
Magnetic bead
Electromagnet
Internal
rod
Sample
Catalytic
knob
Nickel
plate
RESULTS
Rotation in one direction
Rotation in opposite direction
No rotation
Figure 9.15 Is the rotation of the internal rod in ATP synthase responsible for ATP synthesis? 30
Number of photons
detected (103) 25 20
Sequential trials

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
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15. Electron transport chain 2 Chemiosmosis
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

16. 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
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17. Fig. 9-17
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:

18. Most cellular respiration requires O2 to produce ATP
Concept 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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19. 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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20. Two common types are alcohol fermentation and lactic acid fermentation
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
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21. 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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22. Fig. 9-18 Figure 9.18 Fermentation 2 ADP + 2 Pi 2 ATP Glucose
Glycolysis
2 Pyruvate
2 NAD+
2 NADH 2
CO2
+ 2 H+
2 Ethanol
2 Acetaldehyde
(a) Alcohol fermentation
2 ADP + 2 Pi
2 ATP
Glucose
Glycolysis
Figure 9.18 Fermentation
2 NAD+
2 NADH
+ 2 H+
2 Pyruvate
2 Lactate
(b) Lactic acid fermentation

23. (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

24. 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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25. (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

26. 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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27. 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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28. 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

29. 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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