Cellular Respiration
Content
Chapter 13 & 14: Respiration
•
•
•
•
•
•
glycolysis
fermentation
the mitochondrion
the citric acid cycle
the electron transport chain and oxidative phosphorylation
ATP synthesis
4th ed: p. 417-435; 451-465
1
(3rd ed: p. 427-433; 436-443; 456-464; 466-467)
Summary of
glycolysis
2
Summary of Glycolysis
1 Glucose (6C)
All reactions occur
• initial energy investment
in the cytoplasm.
(-2 ATPs)
1 Fructose 1,6-bisphosphate (6C)
• cleavage
2 Glyceraldehyde 3-phosphate (3C)
• energy generation
- by the oxidation of 2 G3P => 2 NADH
- by substrate-level phosphorylation (the transfer of
a phosphate from a sugar intermediate to ADP)
=> 4 ATP
2 Pyruvate (3C)
3
Glycolysis: step by step
Glucose (6C)
1) Phosphorylation
of glucose
• ATP consumed
• phosphorylation of C6
Glucose 6-phosphate (6C)
4
Glycolysis: step by step
2) Isomerization of G6P
Fructose 6-phosphate (6C)
5
Glycolysis: step by step
3) Phosphorylation
of F6P
• ATP consumed
• phosphorylation of C1
Fructose 1,6-bisphosphate (6C)
6
Glycolysis: step by step
4) Cleavage of FBP
Dihydroxyacetone phosphate (3C)
+ Glyceraldehyde 3-phosphate (3C)
7
Glycolysis: step by step
5) Isomerization of DHP
(2) Glyceraldehyde 3-phosphate (3C)
8
Glycolysis: step by step
6) Oxidation of G3P
• 2NAD+ reduced to 2NADH
• Pi attached to C1
(2) 1,3-bisphosphoglycerate (3C)
9
Glycolysis: step by step
7) Transfer of 1P from
BPG to ADP
• 2ATP synthesized by
substrate-level
phosphorylation
(2) 3-Phosphoglycerate (3C)
10
Glycolysis: step by step
8) Isomerization of 3PG
(2) 2-Phosphoglycerate (3C)
11
Glycolysis: step by step
9) Dehydration of 2PG
• 2H2O removed
(2) Phosphoenolpyruvate (3C)
12
Glycolysis: step by step
10) Transfer of P from
PEP to ADP
• 2ATP synthesized by
substrate-level
phosphorylation
(2) Pyruvate (3C)
13
Glycolysis
Yield of glycolysis:
2 ATP consumed at the energy investment phase
4 ATP and 2 NADH produced at the energy generation phase
Net yield: 2 ATP + 2 NADH
Under anaerobic conditions (no O2 present):
• pyruvate and NADH are consumed in fermentation
14
+
• NAD is regenerated and used in glycolysis (step 6)
Fermentation
In the absence of oxygen, pyruvate is reduced, driven by the
oxidation of the NADH generated from glycolysis.
In muscle cells
In yeast
2 Pyruvate (3C)
2 Pyruvate (3C)
• NADH => NAD+
2 Lactic acid (3C)
• CO2 removed
2 Acetaldehyde (2C)
• NADH => NAD+
2 Ethanol (2C)
15
Net yield of fermentation: 2 ATP
Fermentation leading to
excretion of lactate
In muscle cells
16
Fermentation leading to
excretion of ethanol and CO2
In yeast
17
Glycolysis
Under aerobic conditions (O2 present):
Pyruvate and NADH
to the mitochondria
• pyruvate is converted to acetyl coenzyme A
and enters the citric acid cycle
• NADH is used to power the oxidative phosphorylation
reactions (the electron transport chain)
18
The mitochondrion
19
The mitochondrion
The mitochondrion (plural mitochondria) is a membraneenclosed organelle of eukaryotic cells that generates most
of the cell's supply of ATP.
• enclosed by a double membrane
• the matrix is the site of the oxidation of pyruvate
and the citric acid cycle
• the inner membrane is the site of the electron transport
chain
and oxidative phosphorylation
20
Matrix
21
The oxidation of pyruvate
Pyruvate + CoenzymeA Acetyl CoA + CO2
Pyruvate (3C) + CoA
• CO2 is removed by hydrolysis, driving
• NAD+ => NADH, and
• the condensation with CoA
Acetyl CoA (2C)
22
Citric Acid Cycle
(The Krebs Cycle)
23
The Citric Acid Cycle: step by step
Acetyl CoA (2C) + Oxaloacetate (4C)
1) Condensation and
citrate synthesis
• driven by the hydrolysis
that removes CoA
Citric acid (6C)
2) Isomerization of CA
Isocitrate (6C)
3) Oxidation of IC
• CO2 removed
• NAD+ reduced to NADH
alpha-ketoglutarate (5C)
24
The Citric Acid Cycle: step by step
4) Oxidation of KG
• CO2 removed
• NAD+ reduced to NADH
• CoA added
Succinyl CoA (4C)
• CoA removed
• GTP synthesis
5) Hydrolysis of SCoA
• GTP is hydrolyzed to GDP
• ATP synthesis
Succinate (4C)
6) Oxidation of SA
• FAD reduced to FADH2
Fumarate (4C)
25
Succinate
HS-CoA
GTP
ADP
Succinyl CoA
GDP
ATP
26
The Citric Acid Cycle: step by step
7) Hydrogenation of FA
• H2O consumed
Malate (4C)
8) Oxidation of MA
• NAD+ reduced to NADH
Oxaloacetate (4C)
Re-enters the cycle
27
Yield of citric acid cycle
2 CO2
(per one turn)
4 CO2
(two pyruvates)
3 NADH
1 FADH2
1 ATP
6 NADH
2 FADH2
2 ATP
X2
ATP
NADH and FADH2
to the e- transport chain
28
Matrix
29
Oxidation of NADH transfers
high-energy electrons
to the electron transport chain
30
Oxidative phosphorylation:
The electron transport chain
The respiratory enzyme complexes in the inner membrane
pump H+ from the matrix into the intermembrane space,
generating a H+ gradient across the inner 31membrane.
Oxidative phosphorylation:
The electron transport chain
• the flow of H+ back into the matrix through ATP
synthase powers ATP synthesis
• the energy that powers the H+ pumps is provided by the
32
loss of electrons (oxidation) of NADH and FADH2
The electron transport chain
• NADH is oxidized
• H+ pumps are powered
• e- lose energy
• final e- acceptor:
1
/2O2 + 2H+
=> H2O
33
The electron transport chain
The respiratory enzyme complexes in the inner membrane
contain a series of electron carriers (co-factors).
•
•
•
•
the electrons move through these carriers
each carrier becomes sequentially reduced and oxidized
H+ pumps are powered
e- lose energy
34
The electron transport chain
e- transfer to A
35
The electron transport chain
e- transfer from B
H+ are picked up from one side of the membrane (the matrix)
and released to the other (into the intermembrane
space).
36
The electron transport chain
• as an e- is transferred from
A to B (B is reduced),
a H+ is picked up from
the matrix
• as an e- is transferred from
B to C (B is oxidized),
the H+ is released into
the intermembrane space
• Result: a H+ gradient across
the inner membrane
37
The electron transport chain:
Cytochrome oxidase complex
38
The electron transport chain
Transport of NADH electrons
1- NADH dehydrogenase complex (I): accepts e2- Cytochrome b-c1 complex (III)
3- Cytochrome oxidase complex (IV)
Transport of FADH2 electrons
(not illustrated)
1- Fe-S complex (II): accepts e- from FADH2
2- Cytochrome b-c1 complex (III)
3- Cytochrome oxidase complex (IV)
39
Electron transport chain:
Transport of NADH electrons
I
III
40
IV
Synthesis of ATP
The H+ gradient generated by the e- transport chain powers
ATP synthase complex.
• as H+ flow back across the inner mitochondrial
membrane into the matrix, the central rotor unit
rotates,
powering ATP synthesis (stator: stationary unit)
• Result: oxidative phosphorylation of ADP to ATP
(coupled to redox reactions of ETC)
41
Synthesis of ATP
42
ATP yield of respiration
per molecule of glucose:
ATP from glycolysis and citric acid cycle: _
ATP from oxidative phosphorylation:
NADH from glycolysis: _
NADH from the oxidation of pyruvate: _
NADH from the citric acid cycle: _
FADH2 from the citric acid cycle: _
• 2.5 ATP / NADH: 25
• 1.5 ATP / FADH2: 3
Total: 32 ATP
In most cells: the 2 NADH generated during glycolysis shuttle
electrons to FADH2 in mitochondria: yield 1.5 ATP each
Actual net yield: 30 ATP 43
ATP yield of fermentation
per molecule of glucose:
ATP from glycolysis: _
NADH from glycolysis: _
But pyruvate is reduced in fermentation
and NADH is oxidized to regenerate NAD+ to
be re-used in another round of glycolysis
Total: _ ATP
44
•
•
•
•
•
•
glycolysis
fermentation
the mitochondrion
the citric acid cycle
the electron transport chain and oxidative phosphorylation
ATP synthesis
4th ed: p. 417-435; 451-465
1
(3rd ed: p. 427-433; 436-443; 456-464; 466-467)
Summary of
glycolysis
2
Summary of Glycolysis
1 Glucose (6C)
All reactions occur
• initial energy investment
in the cytoplasm.
(-2 ATPs)
1 Fructose 1,6-bisphosphate (6C)
• cleavage
2 Glyceraldehyde 3-phosphate (3C)
• energy generation
- by the oxidation of 2 G3P => 2 NADH
- by substrate-level phosphorylation (the transfer of
a phosphate from a sugar intermediate to ADP)
=> 4 ATP
2 Pyruvate (3C)
3
Glycolysis: step by step
Glucose (6C)
1) Phosphorylation
of glucose
• ATP consumed
• phosphorylation of C6
Glucose 6-phosphate (6C)
4
Glycolysis: step by step
2) Isomerization of G6P
Fructose 6-phosphate (6C)
5
Glycolysis: step by step
3) Phosphorylation
of F6P
• ATP consumed
• phosphorylation of C1
Fructose 1,6-bisphosphate (6C)
6
Glycolysis: step by step
4) Cleavage of FBP
Dihydroxyacetone phosphate (3C)
+ Glyceraldehyde 3-phosphate (3C)
7
Glycolysis: step by step
5) Isomerization of DHP
(2) Glyceraldehyde 3-phosphate (3C)
8
Glycolysis: step by step
6) Oxidation of G3P
• 2NAD+ reduced to 2NADH
• Pi attached to C1
(2) 1,3-bisphosphoglycerate (3C)
9
Glycolysis: step by step
7) Transfer of 1P from
BPG to ADP
• 2ATP synthesized by
substrate-level
phosphorylation
(2) 3-Phosphoglycerate (3C)
10
Glycolysis: step by step
8) Isomerization of 3PG
(2) 2-Phosphoglycerate (3C)
11
Glycolysis: step by step
9) Dehydration of 2PG
• 2H2O removed
(2) Phosphoenolpyruvate (3C)
12
Glycolysis: step by step
10) Transfer of P from
PEP to ADP
• 2ATP synthesized by
substrate-level
phosphorylation
(2) Pyruvate (3C)
13
Glycolysis
Yield of glycolysis:
2 ATP consumed at the energy investment phase
4 ATP and 2 NADH produced at the energy generation phase
Net yield: 2 ATP + 2 NADH
Under anaerobic conditions (no O2 present):
• pyruvate and NADH are consumed in fermentation
14
+
• NAD is regenerated and used in glycolysis (step 6)
Fermentation
In the absence of oxygen, pyruvate is reduced, driven by the
oxidation of the NADH generated from glycolysis.
In muscle cells
In yeast
2 Pyruvate (3C)
2 Pyruvate (3C)
• NADH => NAD+
2 Lactic acid (3C)
• CO2 removed
2 Acetaldehyde (2C)
• NADH => NAD+
2 Ethanol (2C)
15
Net yield of fermentation: 2 ATP
Fermentation leading to
excretion of lactate
In muscle cells
16
Fermentation leading to
excretion of ethanol and CO2
In yeast
17
Glycolysis
Under aerobic conditions (O2 present):
Pyruvate and NADH
to the mitochondria
• pyruvate is converted to acetyl coenzyme A
and enters the citric acid cycle
• NADH is used to power the oxidative phosphorylation
reactions (the electron transport chain)
18
The mitochondrion
19
The mitochondrion
The mitochondrion (plural mitochondria) is a membraneenclosed organelle of eukaryotic cells that generates most
of the cell's supply of ATP.
• enclosed by a double membrane
• the matrix is the site of the oxidation of pyruvate
and the citric acid cycle
• the inner membrane is the site of the electron transport
chain
and oxidative phosphorylation
20
Matrix
21
The oxidation of pyruvate
Pyruvate + CoenzymeA Acetyl CoA + CO2
Pyruvate (3C) + CoA
• CO2 is removed by hydrolysis, driving
• NAD+ => NADH, and
• the condensation with CoA
Acetyl CoA (2C)
22
Citric Acid Cycle
(The Krebs Cycle)
23
The Citric Acid Cycle: step by step
Acetyl CoA (2C) + Oxaloacetate (4C)
1) Condensation and
citrate synthesis
• driven by the hydrolysis
that removes CoA
Citric acid (6C)
2) Isomerization of CA
Isocitrate (6C)
3) Oxidation of IC
• CO2 removed
• NAD+ reduced to NADH
alpha-ketoglutarate (5C)
24
The Citric Acid Cycle: step by step
4) Oxidation of KG
• CO2 removed
• NAD+ reduced to NADH
• CoA added
Succinyl CoA (4C)
• CoA removed
• GTP synthesis
5) Hydrolysis of SCoA
• GTP is hydrolyzed to GDP
• ATP synthesis
Succinate (4C)
6) Oxidation of SA
• FAD reduced to FADH2
Fumarate (4C)
25
Succinate
HS-CoA
GTP
ADP
Succinyl CoA
GDP
ATP
26
The Citric Acid Cycle: step by step
7) Hydrogenation of FA
• H2O consumed
Malate (4C)
8) Oxidation of MA
• NAD+ reduced to NADH
Oxaloacetate (4C)
Re-enters the cycle
27
Yield of citric acid cycle
2 CO2
(per one turn)
4 CO2
(two pyruvates)
3 NADH
1 FADH2
1 ATP
6 NADH
2 FADH2
2 ATP
X2
ATP
NADH and FADH2
to the e- transport chain
28
Matrix
29
Oxidation of NADH transfers
high-energy electrons
to the electron transport chain
30
Oxidative phosphorylation:
The electron transport chain
The respiratory enzyme complexes in the inner membrane
pump H+ from the matrix into the intermembrane space,
generating a H+ gradient across the inner 31membrane.
Oxidative phosphorylation:
The electron transport chain
• the flow of H+ back into the matrix through ATP
synthase powers ATP synthesis
• the energy that powers the H+ pumps is provided by the
32
loss of electrons (oxidation) of NADH and FADH2
The electron transport chain
• NADH is oxidized
• H+ pumps are powered
• e- lose energy
• final e- acceptor:
1
/2O2 + 2H+
=> H2O
33
The electron transport chain
The respiratory enzyme complexes in the inner membrane
contain a series of electron carriers (co-factors).
•
•
•
•
the electrons move through these carriers
each carrier becomes sequentially reduced and oxidized
H+ pumps are powered
e- lose energy
34
The electron transport chain
e- transfer to A
35
The electron transport chain
e- transfer from B
H+ are picked up from one side of the membrane (the matrix)
and released to the other (into the intermembrane
space).
36
The electron transport chain
• as an e- is transferred from
A to B (B is reduced),
a H+ is picked up from
the matrix
• as an e- is transferred from
B to C (B is oxidized),
the H+ is released into
the intermembrane space
• Result: a H+ gradient across
the inner membrane
37
The electron transport chain:
Cytochrome oxidase complex
38
The electron transport chain
Transport of NADH electrons
1- NADH dehydrogenase complex (I): accepts e2- Cytochrome b-c1 complex (III)
3- Cytochrome oxidase complex (IV)
Transport of FADH2 electrons
(not illustrated)
1- Fe-S complex (II): accepts e- from FADH2
2- Cytochrome b-c1 complex (III)
3- Cytochrome oxidase complex (IV)
39
Electron transport chain:
Transport of NADH electrons
I
III
40
IV
Synthesis of ATP
The H+ gradient generated by the e- transport chain powers
ATP synthase complex.
• as H+ flow back across the inner mitochondrial
membrane into the matrix, the central rotor unit
rotates,
powering ATP synthesis (stator: stationary unit)
• Result: oxidative phosphorylation of ADP to ATP
(coupled to redox reactions of ETC)
41
Synthesis of ATP
42
ATP yield of respiration
per molecule of glucose:
ATP from glycolysis and citric acid cycle: _
ATP from oxidative phosphorylation:
NADH from glycolysis: _
NADH from the oxidation of pyruvate: _
NADH from the citric acid cycle: _
FADH2 from the citric acid cycle: _
• 2.5 ATP / NADH: 25
• 1.5 ATP / FADH2: 3
Total: 32 ATP
In most cells: the 2 NADH generated during glycolysis shuttle
electrons to FADH2 in mitochondria: yield 1.5 ATP each
Actual net yield: 30 ATP 43
ATP yield of fermentation
per molecule of glucose:
ATP from glycolysis: _
NADH from glycolysis: _
But pyruvate is reduced in fermentation
and NADH is oxidized to regenerate NAD+ to
be re-used in another round of glycolysis
Total: _ ATP
44
