Download Citric acid cycle

Chapter 9
Cellular Respiration:
Harvesting Chemical Energy
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• The giant panda
– Obtains energy for its cells by eating plants
Figure 9.1
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• Energy
– Flows into an ecosystem as sunlight and
leaves as heat
Light energy
ECOSYSTEM
Photosynthesis
in chloroplasts
Organic
CO2 + H2O
+ O2
Cellular
molecules
respiration
in mitochondria
ATP
powers most cellular work
Figure 9.2
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Heat
energy
• Concept 9.1: Catabolic pathways yield energy
by oxidizing organic fuels
Catabolic Pathways and Production of ATP
• The breakdown of organic molecules is
exergonic
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• One catabolic process, fermentation
– Is a partial degradation of sugars that occurs
without oxygen
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• Cellular respiration
– Is the most prevalent and efficient catabolic
pathway
– Consumes oxygen and organic molecules
such as glucose
– Yields ATP
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• To keep working
– Cells must regenerate ATP
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Redox Reactions: Oxidation and Reduction
• How do the catabolic pathways that
decompose fuels yield energy?
• the transfer of electrons – the relocation of
electrons releases energy stored in organic
molecules, which is ultimately used to
synthesize ATP.
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The Principle of Redox
• Redox reactions
– Transfer electrons from one reactant to
another by oxidation and reduction
• In oxidation
– A substance loses electrons, or is oxidized
• In reduction
– A substance gains electrons, or is reduced
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• Examples of redox reactions
becomes oxidized
(loses electron)
Na
+
Reducing agent
Cl
Oxidizing agent
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Na+
+
becomes reduced
(gains electron)
Cl–
• Some redox reactions
– Do not completely exchange electrons
– Change the degree of electron sharing in
covalent bonds
Products
Reactants
becomes oxidized
+
CH4
CO
2O2
+
Energy
2 H2O
becomes reduced
O
O
C
O
H
O
O
H
H
H
C
+
2
H
H
Methane
(reducing
agent)
Oxygen
(oxidizing
agent)
Figure 9.3
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Carbon dioxide
Water
Oxidation of Organic Fuel Molecules During
Cellular Respiration
• During cellular respiration
– Glucose is oxidized and oxygen is reduced
becomes oxidized
C6H12O6 + 6O2
6CO2 + 6H2O + Energy
becomes reduced
• Oxygen is so electronegative, one of the most potent oxidizing agents
• Hydrogen is transferred from glucose to oxygen
- electrons are transferred to a lower energy state.
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Stepwise Energy Harvest via NAD+ and the Electron
Transport Chain
• Cellular respiration
– Oxidizes glucose in a series of steps, not a single
explosive step
– Electrons travels with a proton as a hydrogen atom
– The hydrogen atoms are not transferred directly to
oxygen, but instead are passed first to an electron
carrier, a coenzyme called NAD (nicotinamide adenine
dinucleotide)
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• Electrons from organic compounds
– Are usually first transferred to NAD+, a coenzyme, an
electron acceptor
2 e– + 2 H+
NAD+
Dehydrogenase
O
NH2
H
C
CH2
O
O–
O
O P
O
H
–
O P O HO
O
N+ Nicotinamide
(oxidized form)
H
OH
HO
CH2
H
HO
H
OH
(Nicotinamide adenine dinucleotide)
N
H
N
Reduction of NAD+
+ 2[H]
(from food) Oxidation of NADH
N
H
Figure 9.4
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N
H+
NADH
H O
C
H
NH2
N
O
2 e– + H+
NH2
Nicotinamide
(reduced form)
+ H+
• How NAD+ trap electrons from glucose
- Dehydrogenase remove 2 hydrogen atoms (2
electrons and 2 protons) from substrate, but
delivers the 2 electrons along with 1 proton to
its coenzyme, NAD+
• H-C-OH +
NAD+
Dehydrogenase
C=O + NADH + H+
• NADH, the reduced form of NAD+
– Passes the electrons to the electron transport
chain
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• If electron transfer is not stepwise
– A large release of energy occurs
– As in the reaction of hydrogen and oxygen to
form water
Free energy, G
H2 + 1/2 O2
Figure 9.5 A
Explosive
release of
heat and light
energy
H2O
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(a) Uncontrolled reaction
• The electron transport chain
– Passes electrons in a series of steps instead of
in one explosive reaction
– Uses the energy from the electron transfer to
form ATP
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2H
1/
+
2
O2
1/
O2
(from food via NADH)
Free energy, G
2 H+ + 2 e–
Controlled
release of
energy for
synthesis of
ATP
ATP
ATP
ATP
2 e–
2
H+
H2O
Figure 9.5 B
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(b) Cellular respiration
2
The Stages of Cellular Respiration: A Preview
• Respiration is a cumulative function of three
metabolic stages
– Glycolysis
– The citric acid cycle
– Oxidative phosphorylation
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• Glycolysis
– Breaks down glucose into two molecules of
pyruvate
• The citric acid cycle
– Completes the breakdown of glucose
• Oxidative phosphorylation
– Is driven by the electron transport chain
– Generates ATP
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• An overview of cellular respiration
Electrons carried
via NADH and
FADH2
Electrons
carried
via NADH
Citric
acid
cycle
Glycolsis
Pyruvate
Glucose
Cytosol
Mitochondrion
ATP
Figure 9.6
Oxidative
phosphorylation:
electron
transport and
chemiosmosis
Substrate-level
phosphorylation
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ATP
Substrate-level
phosphorylation
ATP
Oxidative
phosphorylation
• Both glycolysis and the citric acid cycle
– Can generate ATP by substrate-level
phosphorylation
Enzyme
Enzyme
ADP
P
Substrate
+
Figure 9.7
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Product
ATP
• Concept 9.2: Glycolysis harvests energy by
oxidizing glucose to pyruvate
• Glycolysis
– Means “splitting of sugar”
– Breaks down glucose into pyruvate
– Occurs in the cytoplasm of the cell
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• Glycolysis consists of two major phases
– Energy investment phase
– Energy payoff phase
Citric
acid
cycle
Glycolysis
Oxidative
phosphorylation
ATP
ATP
ATP
Energy investment phase
Glucose
2 ATP + 2 P
2 ATP
used
Energy payoff phase
4 ADP + 4 P
2 NAD+ + 4 e- + 4 H
+
4 ATP formed
2 NADH + 2 H+
2 Pyruvate + 2 H2O
Glucose
4 ATP formed – 2 ATP used
Figure 9.8
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2 NAD+ + 4 e– + 4 H
+
2 Pyruvate + 2 H2O
2 ATP + 2 H+
2 NADH
•
A closer look at the energy
investment phase
CH2OH
HH
H
HO H
HO
OH
H OH
Glycolysis
Glucose
ATP
Phosphorylation trap sugar in the cell and
make glucose more reactive
1
Hexokinase
ADP
CH2OH P
HH OH
OH H
HO
H OH
Glucose-6-phosphate
2
Phosphoglucoisomerase
CH2O P
O CH2OH
H HO
HO
H
HO H
Fructose-6-phosphate
Key step for regulation; allosterically
regulated by ATP and its product
ATP
3
Phosphofructokinase
ADP
P O CH2 O CH2 O P
HO
H
OH
HO H
Fructose1, 6-bisphosphate
4
Aldolase
Only glyceraldehyde-3-phosphate are used.
Cleavage of six-carbon sugar into two G3P
Figure 9.9 A
5
H
P O CH2 Isomerase
C O
C O
CHOH
CH2OH
CH2 O P
Dihydroxyacetone
phosphate
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Glyceraldehyde3-phosphate
Citric
Oxidative
acid
cycle phosphorylation
•
A closer look at the energy payoff
phase
6
Triose phosphate
dehydrogenase
2 NAD+
2 Pi
2 NADH
+ 2 H+
2
P
O C O
CHOH
Carbonyl group of a sugar is oxidized to a carboxyl group.
Substrate-level phosphorylation
CH2 O P
1, 3-Bisphosphoglycerate
2 ADP
7
Phosphoglycerokinase
2 ATP
O–
2
C
CHOH
CH2 O P
3-Phosphoglycerate
8
Phosphoglyceromutase
Relocation of the remaining phosphate group
2
O–
C
O
H C O
Make a double bond by extracting a water molecule
P
CH2OH
2-Phosphoglycerate
9
Enolase
2H O
2
2
O–
C O
C O
P
CH2
Phosphoenolpyruvate
2 ADP
10
Pyruvate kinase
Second substrate-level phosphorylation
Transfer of phosphate from PEP to ADP.
2NADH : oxidative phosphorylation
Pyruvate : citric acid cycle with O2,
fermentation without O2
2 ATP
2
O–
C O
C O
Figure 9.8 B
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CH3
Pyruvate
Phosphate ion in
cytosol
• Concept 9.3: The citric acid cycle completes
the energy-yielding oxidation of organic
molecules
• The citric acid cycle
– Takes place in the matrix of the mitochondrion
– In prokaryotic cells, In the cytosol
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• Before the citric acid cycle can begin
– Pyruvate must first be converted to acetyl CoA, which
links the cycle to glycolysis
– Fully oxidized carboxyl group is removed as a CO2
– The remaining two-carbon fragment is oxidized to
acetate. The extracted electrons are transferred to
NAD+, forming NADH.
– Coenzyme A derived from vitamin B is attached to the
actetate by an unstable bond that make the acetyl
group very reactive. High potential energy.
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CYTOSOL
MITOCHONDRION
NAD+
NADH
+ H+
O–
S
CoA
C
O
2
C
C
O
O
1
3
CH3
Pyruvate
Transport protein
Figure 9.10
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CH3
Acetyle CoA
CO2
Coenzyme A
• An overview of the citric acid cycle
Pyruvate
(from glycolysis,
2 molecules per glucose)
Glycolysis
Citric
acid
cycle
ATP
ATP
Oxidative
phosphorylatio
n
ATP
CO2
CoA
NADH
+ 3 H+ Acetyle CoA
CoA
CoA
Citric
acid
cycle
2 CO2
3 NAD+
FADH2
FAD
3 NADH
+ 3 H+
ADP + P i
ATP
Figure 9.11
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• A closer look at the citric acid cycle
Glycolysis
Citric
Oxidative
acid phosphorylation
cycle
S
CoA
C
O
CH3
Acetyl CoA
CoA SH
O
NADH
+ H+
C COO–
COO–
1
CH2
COO–
NAD+
8 Oxaloacetate
HO C
COO–
COO–
CH2
COO–
HO CH
H2O
CH2
CH2
2
HC COO–
COO–
Malate
Figure
CH2
HO
Citrate
9.12
COO–
Isocitrate
COO–
COO–
CH
CO2
Citric
acid
cycle
7
H2O
3
NAD+
COO–
Fumarate
HC
CH2
CoA SH
6
CoA SH
COO–
FAD
CH2
CH2
COO–
C O
Succinate
4
NADH
+ H+
C O
COO–
CH2
5
CH2
FADH2
COO–
Isocitrate is oxidized, reducing
NAD+ to NADH.
a-Ketoglutarate
CH2
COO–
Two hydrogens are transferred
to FAD, forming fADH2 and oxidizing
succinate.
CH
Pi
S
CoA
GTP GDP Succinyl
NAD+
CO2
NADH
+ H+
CoA
ADP
ATP
Figure 9.12
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CoA is displaced by a phosphate group, which
transferred to GDP, forming GTP.
• Concept 9.4: During oxidative phosphorylation,
chemiosmosis couples electron transport to
ATP synthesis
• Glycolysis and the citric acid cycle produce only 4 ATP
molecules per glucose, all by substrate-level
phosphorylation: 2 net ATP from glycolysis and 2 ATP from
the citric acid cycle.
• NADH and FADH2
– Donate electrons to the electron transport chain, which
powers ATP synthesis via oxidative phosphorylation
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The Pathway of Electron Transport
•
In the electron transport chain
–
•
Electrons from NADH and FADH2 lose energy in several steps
At the end of the chain
–
Electrons are passed to oxygen molecule
not oxygen atoms, forming water
•
Electron transport chain is embedded in the inner membrane of
the mitochondrion forming multiprotein complexes (I – IV).
•
Flavin mononucleotide (FMN), iron-sulfur protein, ubiquinone (Q,
coenzyme Q, mobile within the membrane)
•
Cytochromes contain a heme group which has an iron atom that
accepts and donates electrons, similar to the heme group in
hemoglobin. Depending on heme groups, different cytochromes!
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•
One third less ATP synthesis
5
0
NAD
H
2 e–
NAD+
FADH
2
4
0
FM
N

Fe•
S
Q
2
e–
One third less ATP synthesis
FA
D
Multiprotein
complexes
FA
D
Fe• 

S
3
0
2
0
1
0
0
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Cyt
b


Fe•
S
Cyt
c1
IV
Cyt
c
Cyt
a
Cyt
a3
2 e–
(from
NADH
or FADH2)
2 H+ +
1/
2
O2
H2
O
Chemiosmosis: The Energy-Coupling Mechanism
• ATP synthase is the enzyme that actually makes ATP
• Driving power is a difference in the concentration of H+
Four parts; Rotor, stator, internal
rod, catalytic knob
INTERMEMBRANE SPACE
H+
Stator
In mitochondrial and chloroplast
membranes, plasma membranes
of prokaryotes
Rotor
Internal
rod
Catalytic
knob
ADP
+
Pi
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ATP
MITOCHONDRIAL MATRIX
Is the rotation of the internal rod in ATP synthase
reponsible for ATP synthesis?
EXPERIMENT
Magnetic bead
Electromagnet
Sample
Internal
rod
Catalytic
knob
Nickel
plate
RESULTS
Number of photons
detected (103)
Rotation in one direction
Rotation in opposite direction
No rotation
30
25
The direction of rotation of one part
of the protein complex is
responsible for either ATP synthesis
or ATP hydrolysis
20
The smallest rotatory motor known in nature
0
Sequential trials
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How does the inner membrane generate the H+ gradient ?
• Along the electron transport chain
– Electron transfer causes protein complexes to pump
H+ from the mitochondrial matrix to the intermembrane
space
• The resulting H+ gradient
– Stores energy
– Drives chemiosmosis in ATP synthase
– Is referred to as a proton-motive force
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• Chemiosmosis and the electron transport chain
Oxidative
phosphorylation.
electron transport
and chemiosmosis
Glycolysis
ATP
Inner
Mitochondrial
membrane
ATP
ATP
H+
H+
H+
Intermembrane
space
Protein complex
of electron
carners
Q
I
Inner
mitochondrial
membrane
IV
III
ATP
synthase
II
FADH2
NADH+
Mitochondrial
matrix
H+
Cyt c
FAD+
NAD+
2 H+ + 1/2 O2
H2O
ADP +
(Carrying electrons
from, food)
ATP
Pi
H+
Chemiosmosis
Electron transport chain
+
ATP
synthesis
powered by the flow
Electron transport and pumping of protons (H ),
+
+
which create an H gradient across the membrane Of H back across the membrane
Figure 9.15
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Oxidative phosphorylation
• The chain is an energy converter that uses the exergonic
flow of electrons from NADH and FADH2 to pump H+ from
the mitochondrial matrix to the intermembrane space
• The proton-motive force drives H+ back across the
membrane through the H+ channels provided by ATP
synthases.
• Chloroplast in photosysntesis, light drive electron flow
• Prokaryotes generate H+ gradient acrosss their plasma
membrane
• Chemiosmosis (peter Mitchell, Nobel prize in 1978)
– Is an energy-coupling mechanism that uses energy in
the form of a H+ gradient across a membrane to drive
cellular work
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An Accounting of ATP Production by Cellular
Respiration
• During respiration, most energy flows in this
sequence
– Glucose to NADH to electron transport chain to
proton-motive force to ATP
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• There are three main processes in this
metabolic enterprise
Electron shuttles
span membrane
CYTOSOL
MITOCHONDRION
2 NADH
or
2 FADH2
2 NADH
2 NADH
Glycolysis
Glucose
2
Pyruvate
6 NADH
Citric
acid
cycle
2
Acetyl
CoA
+ 2 ATP
by substrate-level
phosphorylation
Maximum per glucose:
+ 2 ATP
2 FADH2
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
+ about 32 or 34 ATP
by substrate-level by oxidative phosphorylation, depending
on which shuttle transports electrons
phosphorylation
from NADH in cytosol
About
36 or 38 ATP
Figure 9.16
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• About 40% of the energy in a glucose molecule
– Is transferred to ATP during cellular respiration,
making approximately 38 ATP
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• Concept 9.5: Fermentation enables some cells
to produce ATP without the use of oxygen
• Cellular respiration
– Relies on oxygen to produce ATP
• In the absence of oxygen
– Cells can still produce ATP through
fermentation
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• Glycolysis
– Can produce ATP with or without oxygen, in
aerobic or anaerobic conditions
– Couples with fermentation to produce ATP
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Types of Fermentation
• Fermentation consists of
– Glycolysis plus reactions that regenerate NAD+,
which can be reused by glyocolysis
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• In alcohol fermentation
– Pyruvate is converted to ethanol in two steps,
one of which releases CO2
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• During lactic acid fermentation
– Pyruvate is reduced directly to NADH to form
lactate as a waste product
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2 ADP + 2
P1
2 ATP
O–
C O
Glucose
Glycolysis
C O
CH3
2 Pyruvate
2 NADH
2 NAD+
H
2 CO2
H
H C OH
C O
CH3
CH3
2 Ethanol
2 Acetaldehyde
(a) Alcohol fermentation
2 ADP + 2
Glucose
P1
2 ATP
Glycolysis
O–
C O
C O
O
2 NAD+
2 NADH
C O
H
C OH
CH3
2 Lactate
Figure 9.17
(b) Lactic acid fermentation
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CH3
Fermentation and Cellular Respiration Compared
• Both fermentation and cellular respiration
– Use glycolysis to oxidize glucose and other
organic fuels to pyruvate
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• Fermentation and cellular respiration
– Differ in their final electron acceptor
• Cellular respiration
– Produces more ATP
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• Pyruvate is a key juncture in catabolism
Glucose
CYTOSOL
Pyruvate
No O2 present
Fermentation
O2 present
Cellular respiration
MITOCHONDRION
Ethanol
or
lactate
Figure 9.18
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Acetyl CoA
Citric
acid
cycle
The Evolutionary Significance of Glycolysis
• Glycolysis
– Occurs in nearly all organisms
– Probably evolved in ancient prokaryotes before
there was oxygen in the atmosphere
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• Concept 9.6: Glycolysis and the citric acid
cycle connect to many other metabolic
pathways
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The Versatility of Catabolism
• Catabolic pathways
– Funnel electrons from many kinds of organic
molecules into cellular respiration
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• The catabolism of various molecules from food
Proteins
Carbohydrates
Amino
acids
Sugars
Fats
Glycerol
Glycolysis
Glucose
Glyceraldehyde-3- P
NH3
Pyruvate
Acetyl CoA
Citric
acid
cycle
Figure 9.19
Oxidative
phosphorylation
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Fatty
acids
Biosynthesis (Anabolic Pathways)
• The body
– Uses small molecules to build other
substances
• These small molecules
– May come directly from food or through
glycolysis or the citric acid cycle
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Regulation of Cellular Respiration via Feedback
Mechanisms
• Cellular respiration
– Is controlled by allosteric enzymes at key
points in glycolysis and the citric acid cycle
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• The control of cellular respiration
Glucose
Glycolysis
Fructose-6-phosphate
–
Inhibits
AMP
Stimulates
+
Phosphofructokinase
–
Fructose-1,6-bisphosphate
Inhibits
Pyruvate
Citrate
ATP
Acetyl CoA
Citric
acid
cycle
Figure 9.20
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Oxidative
phosphorylation