1. Chapter 23 Metabolism and Energy Production
23.1
The Citric Acid Cycle
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2. Citric Acid Cycle The citric acid cycle (stage 3)
Operates under aerobic conditions only.
Oxidizes the two-carbon acetyl group in acetyl CoA to 2CO2.
Produces reduced coenzymes NADH and FADH2 and one ATP directly.

3. Citric Acid Cycle Overview
In the citric acid cycle,
Acetyl (2C) bonds to oxaloacetate (4C) to form citrate (6C).
Oxidation and decarboxylation reactions convert citrate to oxaloacetate.
Oxaloacetate bonds with another acetyl to repeat the cycle.
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4. Copyright © 2007 by Pearson Education, Inc.
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5. Reaction 1 Formation of Citrate
Oxaloacetate
Combines with the two-carbon acetyl group to form citrate.
citrate synthase + +

6. Reaction 2 Isomerization to Isocitrate
Isomerizes to isocitrate.
Has a tertiary —OH group converted to a secondary —OH in isocitrate that can be oxidized.

7. Summary of Reactions 1 and 2
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8. Reaction 3 Oxidative Decarboxylation
Isocitrate
Undergoes decarboxylation (carbon removed as CO2).
Oxidizes the —OH to a ketone releasing H+ and 2e−.
Provides H to reduce coenzyme NAD+ to NADH. + + +
-ketoglutarate

9. Reaction 4 Oxidative Decarboxylation
-Ketoglutarate
Undergoes decarboxylation to form succinyl CoA.
Produces a 4-carbon compound that bonds to CoA.
Provides H+ and 2e− to reduce NAD+ to NADH.
-ketoglutarate succinyl CoA
-ketoglutarate
dehydrogenase +

10. Summary of Reactions 3 and 4
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11. Reaction 5 Hydrolysis Succinyl CoA
Undergoes hydrolysis of the thioester bond.
Provides energy to add phosphate to GDP and form GTP, a high­energy compound.
succinyl CoA
synthetase +
+ GDP + Pi
+ CoASH
+ GTP
ATP
succinate
succinyl CoA

12. Reaction 6 Dehydrogenation
Succinate
Undergoes dehydrogenation.
Loses two H and forms a double bond.
Provides 2H to reduce FAD to FADH2.
succinate dehydrogenase
+ FAD
+ FADH2

13. Summary of Reactions 5 and 6
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14. Reaction 7 Hydration of Fumarate
Undergoes hydration.
Adds water to the double bond.
Is converted to malate.
fumarase

15. Reaction 8 Dehydrogenation
Malate
Undergoes dehydrogenation.
Forms oxaloacetate with a C=O double bond.
Provides 2H that reduce NAD+ to NADH + H+.
malate dehydrogenase
+ NAD+ +

16. Summary of Reactions 7 and 8
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17. Summary of the Citric Acid Cycle
In the citric acid cycle,
An acetyl group bonds with oxaloacetate to form citrate.
Two decarboxylations remove two carbons as 2CO2.
Four oxidations provide hydrogen for 3NADH and one FADH2.
A direct phosphorylation forms GTP (ATP).

18. Overall Chemical Reaction for the Citric Acid Cycle
acetylS-CoA + 3NAD+ + FAD + GDP + Pi + 2H2O
2CO2 + 3NADH + 3H+ + FADH2 + HS-CoA + GTP
One turn of the citric acid cycle produces:
2 CO GTP (1ATP)
3 NADH HS-COA
1 FADH2

19. Learning Check How many of each are produced in one turn of the
citric acid cycle?
A ___ CO2
B. ___ NADH
C. ___ FADH2
D. ___ GTP

20. Solution How many of each are produced in one turn of the
citric acid cycle?
A 2 CO2
B. 3 NADH
C. 1 FADH2
D. 1 GTP

21. Regulation of Citric Acid Cycle
The reaction rate for
the citric acid cycle
Increases when low levels of ATP or NAD+ activate isocitrate dehydrogenase.
Decreases when high levels of ATP or NADH inhibit citrate synthetase (first step in cycle).
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22. Chapter 23 Metabolism and Energy Production
23.2
Electron Carriers
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23. Electron Carriers Electron carriers
Are oxidized and reduced as hydrogen and/or electrons are transferred from one carrier to the next.
Are FMN, Fe-S clusters, Coenzyme Q, and cytochromes.
electron carrier AH2(reduced) electron carrier B (oxidized)
electron carrier A (oxidized) electron carrier BH2(reduced)

24. Electron Carriers Electron carriers
Accept hydrogen and electrons from the reduced coenzymes.
Are oxidized and reduced to provide energy for the synthesis of ATP.
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25. FMN (Flavin mononucleotide)
FMN coenzyme
Contains flavin, ribitol,and phosphate.
Accepts 2H+ + 2e- to form reduced coenzyme FMNH2.
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26. Iron-Sulfur (Fe-S) Clusters
Are groups of proteins containing iron ions and sulfide.
Accept electrons to reduce Fe3+ to Fe2+, and lose electrons to re-oxidize Fe2+ to Fe3+.
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27. Coenzyme Q (Q or CoQ) Coenzyme Q (Q or CoQ) is
A mobile electron carrier derived from quinone.
Reduced when the keto groups accept 2H+ and 2e-.
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28. Cytochromes Cytochromes (cyt) are
Proteins containing heme groups with iron ions.
Fe3+ + 1e Fe2+
Abbreviated as
cyt a, cyt a3, cyt b, cyt c, and cyt c1.
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29. Learning Check Write the abbreviation for each:
A. Reduced form of coenzyme Q.
B. Oxidized form of flavin mononucleotide.
C. Reduced form of iron in cytochrome c.

30. Solution Write the abbreviation for each:
A. Reduced form of coenzyme Q.
CoQH2 or QH2
B. Oxidized form of flavin mononucleotide.
FMN
C. Reduced form of cytochrome c.
Cyt c (Fe2+)

31. Learning Check A. FMNH2 FMN B. Cyt b (Fe3+) Cyt b (Fe2+) C. Q QH2
Indicate whether the electron carrier in each is oxidized or reduced:
A. FMNH2 FMN
B. Cyt b (Fe3+) Cyt b (Fe2+)
C. Q QH2
D. Cyt c (Fe2+) Cyt c (Fe3+)

32. Solution A. FMNH2 FMN oxidized B. Cyt b (Fe3+) Cyt b (Fe2+) reduced
Indicate whether the electron carrier in each is oxidized or reduced:
A. FMNH2 FMN oxidized
B. Cyt b (Fe3+) Cyt b (Fe2+) reduced
C. Q QH2 reduced
D. Cyt c (Fe2+) Cyt c (Fe3+) oxidized

33. Chapter 23 Metabolism and Energy Production
23.3
Electron Transport
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34. Electron Transport Electron transport Uses electron carriers.
Transfers hydrogen ions and electrons from NADH and FADH2 until they combine with oxygen.
Forms H2O.
Produces ATP energy.

35. Electron Transport System
In the electron transport system,
The electron carriers are attached to the inner membrane of the mitochondrion.
There are four protein complexes:
Complex I NADH dehydrogenase
Complex II Succinate dehydrogenase
Complex III CoQ-Cytochrome c reductase
Complex IV Cytochrome c oxidase

36. Electron Transport Chain
Cyt c1
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37. Complex I NADH Dehydrogenase
At Complex I,
Hydrogen and electrons are transferred from NADH to FMN.
NADH + H+ + FMN NAD FMNH2
FMNH2 transfers hydrogen to Fe-S clusters and then to coenzyme Q reducing Q and regenerating FMN.
Q FMNH QH FMN
The overall reaction is
NADH + H Q QH NAD+
QH2, a mobile carrier, transfers hydrogen to
Complex III.

38. Complex II Succinate Dehydrogenase
At Complex II, with a lower energy level than
Complex I,
FADH2 transfers hydrogen and electrons to coenzyme Q.
Q is reduced to QH2 and FAD is regenerated.
FADH Q QH FAD
QH2, a mobile carrier, transfers hydrogen to
Complex III.

39. Complex III CoQ-Cytochrome c reductase
At Complex III,
Electrons are transferred from QH2 to two Cyt b.
Each Cyt b (Fe3+) is reduced to Cyt b (Fe2+).
Q is regenerated.
2Cyt b (Fe3+) + QH Cyt b (Fe2+) + Q + 2H+
Electrons are transferred from Cyt b to Fe-S clusters, to Cyt c1, and to Cyt c, the second mobile carrier.
2Cyt c (Fe3+) + 2Cyt b (Fe2+)
2Cyt c (Fe2+) + 2Cyt b (Fe3+)

40. Complex IV Cytochrome c Oxidase
At Complex IV, electrons are transferred from:
Cyt c to Cyt a.
2Cyt c (Fe2+) + 2Cyt a (Fe3+)
2Cyt a (Fe2+) + 2Cyt c (Fe3+)
Cyt a to Cyt a3.
2Cyt a (Fe2+) + 2Cyt a3 (Fe3+)
2Cyt a (Fe3+) + 2Cyt a3 (Fe2+)
Cyt a3 to oxygen and H+ to form water.
4H+ + O e- (from Cyt a3 ) H2O

41. Learning Check Match each with their function: 1) FMN 2) Q 3) Cyt c
A. Accepts H and electrons from NADH + H+.
B. A mobile carrier between Complex II and III.
C. Carries electrons from Complex I and II to
Complex III.
D. Accepts H and electrons from FADH2.

42. Solution Match each with their function: 1) FMN 2) Q 3) Cyt c
A. 1 Accepts H and electrons from NADH + H+.
B. 3 A mobile carrier between Complex II and III.
C. 2 Carries electrons from Complex I and II to
Complex III.
D. 2 Accepts H and electrons from FADH2.

43. Learning Check Classify each as a product of the
1) Citric acid cycle 2) Electron transport chain
A. CO2
B. FADH2
C. NAD+
D. NADH
E. H2O

44. Solution Classify each as a product of the
1) citric acid cycle 2) electron transport chain
A CO2
B. 1 FADH2
C NAD+
D NADH
E H2O

45. Chapter 23 Metabolism and Energy Production
23.4
Oxidative Phosphorylation and ATP
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46. Chemiosmotic Model In the chemiosmotic model
Complexes I, III, and IV pump protons into the intermembrane space creating a proton gradient.
Protons pass through ATP synthase to return to the matrix.
The flow of protons through ATP synthase provides the energy for ATP synthesis (oxidative phosphorylation):
ADP + Pi + Energy ATP

47. Chemiosmotic Model of Electron Transport
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48. ATP Synthase In ATP synthase
Protons flow back to the matrix through a channel in the F0 complex.
Proton flow provides the energy that drives ATP synthesis by the F1 complex.
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49. ATP Synthase F1 Complex In the F1 complex of ATP synthase
A center subunit () is surrounded by three protein subunits: loose (L), tight (T), and open (O).
Energy from the proton flow through F0 turns the center subunit ().
The shape (conformation) of the three subunits changes.

50. ATP Synthesis in F1 During ATP synthesis
ADP and Pi enter the loose L site.
The center subunit turns changing the L site to a tight T conformation.
ATP is formed in the T site where it remains strongly bound.
The center subunit turns changing the T site to an open O site, which releases the ATP.

51. ATP Synthase F1 Diagram Copyright © 2007 by Pearson Education, Inc.
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52. Learning Check Match the following
1) F0 complex 2) F1 complex 3) L site
4) T site 5) O site
A. Contains subunits for ATP synthesis.
B. Contains the channel for proton flow.
C. The subunit in F1 that binds ADP and Pi.
D. The subunit in F1 that releases ATP.
E. The subunit in F1 where ATP forms.

53. Solution Match the following 1) F0 complex 2) F1 complex 3) L site
4) T site 5) O site
A. 2 Contains subunits for ATP synthesis.
B Contains the channel for proton flow.
C The subunit in F1 that binds ADP and Pi.
D The subunit in F1 that releases ATP.
E The subunit in F1 where ATP forms.

54. Electron Transport and ATP
In electron transport, the energy level decrease for
electrons
From NADH (Complex I) provides sufficient energy for 3ATPs.
NADH + 3ADP + 3Pi NAD ATP
From FADH2 (Complex II) provides sufficient energy for 2ATPs.
FADH2 + 2ADP + 2Pi FAD ATP

55. ATP from Electron Transport
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56. Regulation of Electron Transport
The electron transport system is regulated by
Low levels of ADP, Pi, oxygen, and NADH that decrease electron transport activity.
High levels of ADP that activate electron transport.

57. Chapter 23 Metabolism and Energy Production
23.5
ATP Energy from Glucose
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58. ATP Energy from Glucose
The complete
oxidation of
glucose yields
6 CO2
6 H2O
36 ATP
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59. ATP from Glycolysis In glycolysis
Glucose forms 2 pyruvate, 2 ATP and 2NADH.
NADH produced in the cytoplasm cannot enter the mitochondria.
A shuttle compound (glycerol-3-phosphate) moves hydrogen and electrons into the mitochondria to FAD, which forms FADH2.
Each FADH2 provides 2 ATP.
Glucose pyruvate + 6 ATP

60. ATP from Glycolysis Reaction Pathway ATP for One Glucose
Activation of glucose -2 ATP
Oxidation of 2 NADH (as FADH2) 4 ATP
Direct ADP phosphorylation (two triose) 4 ATP
6 ATP
Summary:
C6H12O pyruvate + 2H2O + 6 ATP
glucose

61. ATP from Two Pyruvate Under aerobic conditions
2 pyruvate are oxidized to 2 acetyl CoA and 2 NADH.
2 NADH enter electron transport to provide 6 ATP.
Summary:
2 Pyruvate Acetyl CoA + 6 ATP

62. ATP from Citric Acid Cycle
One turn of the citric acid cycle provides:
3 NADH x 3 ATP = 9 ATP
1 FADH2 x 2 ATP = 2 ATP
1 GTP x 1 ATP = ATP
Total = ATP
Acetyl CoA CO ATP
For two acetyl CoA from one glucose, two turns of the citric acid cycle produce 24 ATP.
2 Acetyl CoA CO ATP

63. ATP from Citric Acid Cycle
Reaction Pathway ATP (One Glucose)
ATP from Citric Acid Cycle
Oxidation of 2 isocitrate (2NADH) 6 ATP
Oxidation of 2 -ketoglutarate (2NADH) 6 ATP
2 Direct substrate phosphorylations (2GTP) 2 ATP
Oxidation of 2 succinate (2FADH2) 4 ATP
Oxidation of 2 malate (2NADH) 6 ATP
Summary: 2Acetyl CoA CO2 + 2H2O + 24 ATP

64. ATP from Glucose From glycolysis 6 ATP From 2 pyruvate 6 ATP
One glucose molecule undergoing complete oxidation provides:
From glycolysis ATP
From 2 pyruvate ATP
From 2 acetyl CoA ATP
Overall ATP Production for one glucose
C6H12O6 + 6O2 + 36ADP + 36Pi
glucose CO2 + 6H2O + 36ATP

65. Learning Check
Indicate the ATP yield for each under aerobic conditions.
A. Complete oxidation of glucose
B. FADH2
C. Acetyl CoA in citric acid cycle
D. NADH
E. Pyruvate decarboxylation

66. Solution Indicate the ATP yield for each under aerobic conditions.
A. Complete oxidation of glucose ATP
B. FADH ATP
C. Acetyl CoA in citric acid cycle 12 ATP
D. NADH ATP
E. Pyruvate decarboxylation ATP