Download 23 Metabolism and Energy Production

Chapter 23 Metabolism and
Energy Production
23.1
The Citric Acid Cycle
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1
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.
2
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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Reaction 1 Formation of Citrate
Oxaloacetate
 Combines with the two-carbon acetyl group to
form citrate.
COOO
CH3 C SCoA
COO-
+ C O
citrate
synthase
CH2
COOacetyl CoA
oxaloacetate
CH2
HO C COO-
+
HSCoA
H C H
COOcitrate
5
Reaction 2 Isomerization to
Isocitrate
Citrate
 Isomerizes to isocitrate.
 Has a tertiary —OH group converted to a
secondary —OH in isocitrate that can be oxidized.
COO
-
CH2
HO C COOH C H
COO
citrate
-
COO-
-
COO
H2O
CH2
H2O
-
C COO
aconitase
aconitase
CH
-
COO
aconitate
CH2
H C COOHO C H
COOisocitrate
6
Summary of Reactions 1 and 2
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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.
COOisocitrate
dehydrogenase
CH2
H C COO-
+ NAD+
COOCH2
H C H
HO C H
C O
COO-
COO-
isocitrate
+
CO2 + NADH
-ketoglutarate
8
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.
COO-ketoglutarate
dehydrogenase
CH2
COOCH2
CH2 + NAD+
CH2
C O
C O
COO-
+ CoASH
-ketoglutarate
S
+ CO2 + NADH
CoA
succinyl CoA
9
Summary of Reactions 3 and 4
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Reaction 5 Hydrolysis
Succinyl CoA
 Undergoes hydrolysis of the thioester bond.
 Provides energy to add phosphate to GDP and form
GTP, a highenergy compound.
COOCH2
succinyl CoA
synthetase
CH2 + GDP + Pi
C O
COOCH2
CH2
+ GTP
COO-
S CoA
succinyl CoA
++ CoASH
CoA
ATP
succinate
11
Reaction 6 Dehydrogenation
Succinate

Undergoes dehydrogenation.

Loses two H and forms a double bond.

Provides 2H to reduce FAD to FADH2.
COOCH2
COO+ FAD
CH2
succinate
dehydrogenase
C H
H C
-
COO
succinate
+ FADH2
COOfumarate
12
Summary of Reactions 5 and 6
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Reaction 7 Hydration of Fumarate
Fumarate
 Undergoes hydration.
 Adds water to the double bond.
 Is converted to malate.
COO-
COO-
C H
H C
fumarase
+
COOfumarate
H2O
HO C
H
H C H
COOmalate
14
Reaction 8 Dehydrogenation
Malate
 Undergoes dehydrogenation.
 Forms oxaloacetate with a C=O double bond.
 Provides 2H that reduce NAD+ to NADH + H+.
COO-
malate
dehydrogenase
HO C H + NAD+
C O + NADH + H+
CH2
H C H
-
COO
malate
COO-
COOoxaloacetate
15
Summary of Reactions 7 and 8
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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).
17
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 CO2
1 GTP (1ATP)
3 NADH
1 HS-COA
1 FADH2
18
Learning Check
How many of each are produced in one turn of the
citric acid cycle?
A ___ CO2
B. ___ NADH
C. ___ FADH2
D. ___ GTP
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Solution
How many of each are produced in one turn of the
citric acid cycle?
A 2
B. 3
C. 1
D. 1
CO2
NADH
FADH2
GTP
20
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).
21
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Chapter 23 Metabolism and
Energy Production
23.2
Electron Carriers
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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)
23
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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FMN (Flavin mononucleotide)
FMN coenzyme
 Contains
flavin,
ribitol,and
phosphate.
 Accepts 2H+
+ 2e- to form
reduced
coenzyme
FMNH2.
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Iron-Sulfur (Fe-S) Clusters
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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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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Cytochromes
Cytochromes (cyt) are
 Proteins containing
heme groups with
iron ions.
Fe3+ + 1eFe2+
 Abbreviated as
cyt a, cyt a3, cyt b,
cyt c, and cyt c1.
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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.
29
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+)
30
Learning Check
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+)
31
Solution
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
D. Cyt c (Fe2+)
Cyt c (Fe3+) oxidized
reduced
32
Chapter 23 Metabolism and
Energy Production
23.3
Electron Transport
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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.
34
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
35
Electron Transport Chain
Cyt
c1
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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 + FMNH2
QH2 + FMN
 The overall reaction is
NADH + H+ + Q
QH2 + NAD+
 QH2, a mobile carrier, transfers hydrogen to
Complex III.
37
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.
FADH2 + Q
QH2 + FAD
 QH2, a mobile carrier, transfers hydrogen to
Complex III.
38
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+) + QH2
2Cyt 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+)
39
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+ + O2 + 4e- (from Cyt a3 )
2H2O
40
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.
41
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.
42
Learning Check
Classify each as a product of the
1) Citric acid cycle 2) Electron transport chain
A.
B.
C.
D.
E.
CO2
FADH2
NAD+
NADH
H2O
43
Solution
Classify each as a product of the
1) citric acid cycle 2) electron transport chain
A.
B.
C.
D.
E.
1
1
2
1
2
CO2
FADH2
NAD+
NADH
H2O
44
Chapter 23 Metabolism and Energy
Production
23.4
Oxidative Phosphorylation and ATP
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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
46
Chemiosmotic Model of Electron
Transport
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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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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.
49
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.
50
ATP Synthase F1 Diagram
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Learning Check
Match the following
1) F0 complex
2) F1 complex
4) T site
5) O site
A.
B.
C.
D.
E.
3) L site
Contains subunits for ATP synthesis.
Contains the channel for proton flow.
The subunit in F1 that binds ADP and Pi.
The subunit in F1 that releases ATP.
The subunit in F1 where ATP forms.
52
Solution
Match the following
1) F0 complex
2) F1 complex
4) T site
5) O site
A.
B.
C.
D.
E.
2
1
3
5
4
3) L site
Contains subunits for ATP synthesis.
Contains the channel for proton flow.
The subunit in F1 that binds ADP and Pi.
The subunit in F1 that releases ATP.
The subunit in F1 where ATP forms.
53
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+ + 3ATP
 From FADH2 (Complex II) provides sufficient energy
for 2ATPs.
FADH2 + 2ADP + 2Pi
FAD
+ 2ATP
54
ATP from Electron Transport
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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.
56
Chapter 23 Metabolism and Energy
Production
23.5
ATP Energy from Glucose
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ATP Energy from Glucose
The complete
oxidation of
glucose yields
 6 CO2
 6 H2O
 36 ATP
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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
2 pyruvate + 6 ATP
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ATP from Glycolysis
Reaction Pathway
ATP for One Glucose
ATP from Glycolysis
Activation of glucose
-2 ATP
Oxidation of 2 NADH (as FADH2)
4 ATP
Direct ADP phosphorylation (two triose) 4 ATP
6 ATP
Summary:
C6H12O6
2 pyruvate + 2H2O + 6 ATP
glucose
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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
2 Acetyl CoA + 6 ATP
61
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
=
1 ATP
Total
=
12 ATP
Acetyl CoA
2 CO2 + 12 ATP
 For two acetyl CoA from one glucose, two turns of the
citric acid cycle produce 24 ATP.
2 Acetyl CoA
4 CO2 + 24 ATP
62
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
4CO2 + 2H2O + 24 ATP
63
ATP from Glucose
One glucose molecule undergoing complete oxidation
provides:
From glycolysis
6 ATP
From 2 pyruvate
6 ATP
From 2 acetyl CoA
24 ATP
Overall ATP Production for one glucose
C6H12O6 + 6O2 + 36ADP + 36Pi
glucose
6CO2 + 6H2O + 36ATP
64
Learning Check
Indicate the ATP yield for each under aerobic conditions.
A.
B.
C.
D.
E.
Complete oxidation of glucose
FADH2
Acetyl CoA in citric acid cycle
NADH
Pyruvate decarboxylation
65
Solution
Indicate the ATP yield for each under aerobic conditions.
A.
B.
C.
D.
E.
Complete oxidation of glucose
FADH2
Acetyl CoA in citric acid cycle
NADH
Pyruvate decarboxylation
36 ATP
2 ATP
12 ATP
3 ATP
3 ATP
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