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Chapter 9
Cellular Respiration:
Harvesting Chemical Energy
高醫 生物醫學暨環境生物學系
助理教授 張學偉
http://genomed.dlearn.kmu.edu.tw
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• 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
• To keep working, cells must regenerate ATP
本圖補充
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• An overview of cellular respiration
Electrons carried
via NADH and
FADH2
Electrons
carried
via NADH
Citric
acid
cycle
Glycolysis
Pyruvate
Glucose
Cytosol
Mitochondrion
ATP
Figure 9.6
Oxidative
phosphorylation:
electron
transport and
chemiosmosis
Substrate-level
phosphorylation
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
ATP
Substrate-level
phosphorylation
ATP
Oxidative
phosphorylation
Concept
1: Catabolic pathways yield energy by oxidizing organic fuels
2: Glycolysis harvests energy by oxidizing glucose to
pyruvate
3: The citric acid cycle completes the energy-yielding
oxidation of organic molecules
4: During oxidative phosphorylation, chemiosmosis couples
electron transport to ATP synthesis
5: Fermentation enables some cells to produce ATP without
the use of oxygen
6: Glycolysis and the citric acid cycle connect to many other
metabolic pathways
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• Concept 9.1: Catabolic pathways yield energy
by oxidizing organic fuels
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Catabolic Pathways and Production of ATP
Catabolic pathways (異化)
yield energy by oxidizing
organic fuels
同化作用
本圖為補充
exergonic (產能的)
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endergonic 耗能的
• One catabolic process, fermentation (發酵)
– Is a partial degradation of sugars that occurs
without oxygen
稍後再講
Conecept 5: Fermentation enables some cells to
produce ATP without the use of oxygen
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• Cellular respiration
– Is the most prevalent and efficient catabolic
pathway
– Consumes oxygen (with O2 as the ultimate
electron acceptor) and organic molecules such
as glucose
– Yields ATP
It is called cellular respiration to distinguish it from the
respiration of breathing.
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Redox Reactions: Oxidation and Reduction
• Catabolic pathways yield energy
– Due to the transfer of electrons
The Principle of Redox
• Redox reactions
– Transfer electrons from one reactant to another
by oxidation and reduction
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Definition of Oxidation & Reduction and its agent
• In oxidation
– A substance loses electrons, or is oxidized
Reducting Agent
• In reduction
– A substance gains electrons, or is reduced
Oxidating Agent
becomes oxidized
(loses electron)
Na
+
Cl
Na+
+
becomes reduced
(gains electron)
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Cl–
• Some redox reactions
– Do not completely exchange electrons
– Change the degree of electron sharing in covalent
bonds 注意 : blue ball位置
Products
Reactants
becomes oxidized
+
CH4
2O2
2 H2O
O
O
C
O
H
O
H
H
H
O
注意 : blue ball位置
H
Methane
(reducing
agent)
+
Energy
becomes reduced
H
C
+
CO2
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 in a series of steps and oxygen is reduced
becomes oxidized
C6H12O6 + 6O2
6CO2 + 6H2O + Energy △G = - 686 Kcal
becomes reduced
△G < 0
1. spontaneous reaction (without an input of energy)
2. Liberating energy
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Stepwise Energy Harvest via NAD+ and the Electron
Transport Chain
NAD+ = Nicotinamide adenine dinucleotide
2 e– + 2 H+
NAD+
H
O
O–
O
O P
O
H
–
O P O HO
NH2
O
N+ Nicotinamide
(oxidized form)
H
OH
HO
CH2
O
H
HO
H
OH
N
H
H
+ 2[H]
• Nucleosides = Sugar
(from food) Oxidation of NADH
phosphate)
N
H
N
Reduction of NAD+
NH2
N
H+
NADH
• Nucleotide
= Base + Sugar
Dehydrogenase
O + Phosphate
O
C
CH2
2 e– + H+
adenine
Figure 9.4
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H
C NH2
+ Base
(no
N
Nicotinamide
(reduced form)
+
H+
• Electrons from organic compounds
– Are usually first transferred to NAD+, a coenzyme
electron
2
e– +
proton
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
N
H
H
HO
N
H
OH
Reduction of NAD+
+ 2[H]
(from food) Oxidation of NADH
Hydrogen
atom
H O
C
H
N
H+
NADH
NH2
+
H+
Nicotinamide
(reduced form)
NH2
N
O
2 e– + H+
N
H
2H
NAD+ + H+ +2e= NAD+ + 2H
Figure 9.4
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 2H+ +2e- (oxidation)
 NADH (reduction)
 NADH + H+
Ex. A
 B + 2H+ +2e- (oxidation)
(+) FAD + 2H+ +2e-  FADH2
(reduction)
=
A+ FAD <=> B+ FADH2
A+ FAD <=> B+ FADH2
A+ NAD(P) <=> B+ NAD(P)H
A is the electron donor (so it is oxidized)
FAD & NAD(P) is the electron acceptor (so it is reduced).
The products of the reaction are B (oxidized state)
FADH2 or NAD(P)H (reduced state) .
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圖形為補充
• NADH 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
比較 The electron transport chain
2H
• Passes electrons in a
series of steps instead of
in one explosive reaction
2
O2
1/
O2
(from food via NADH)
2 H+ + 2 e–
Controlled
release of
energy for
synthesis of
ATP
Free energy, G
• Uses the energy from the
electron transfer to form
ATP
1/
+
ATP
ATP
ATP
2 e–
2
H+
H2O
Figure 9.5 B
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(b) Cellular respiration
2
• An overview of cellular respiration
Electrons carried
via NADH and
FADH2
Electrons
carried
via NADH
1
2
Glycolsis
Pyruvate
Glucose
Cytosol
Oxidative
3phosphorylation:
electron
transport and
chemiosmosis
Mitochondrion
ATP
Figure 9.6
Citric
acid
cycle
Substrate-level
phosphorylation
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ATP
Substrate-level
phosphorylation
ATP
Oxidative
phosphorylation
• 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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substrate-level phosphorylation
• generate ATP from glycolysis and TCA cycle
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
ATP
Citric
acid
cycle
Oxidative
phosphorylation
ATP
ATP
Energy investment phase
• Glycolysis consists of
two major phases
Glucose
2 ATP + 2
– Energy investment
phase
used
2 ATP
Energy payoff phase
4 ADP + 4
– Energy payoff
phase
P
4 ATP
P
formed
2 NADH
2 NAD+ + 4 e- + 4 H +
+ 2 H+
2 Pyruvate + 2 H2O
Figure 9.8
Net Rx
Glucose
4 ATP formed – 2 ATP used
2 NAD+ + 4 e– + 4 H +
2 Pyruvate + 2 H2O
2 ATP
+ 2 H+
2 NADH
Net Rx: Glucose + 2ADP+ 2Pi + NAD+ 2 Pyruvate + 2ATP + 2NADH + 2 H+
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investment phase
payoff phase
Glycolysis
Citric
acid
cycle
Oxidative
phosphorylation
2
CH2 O P
1, 3-Bisphosphoglycerate
2 ADP
7
Phosphoglycerokinase
ADP
2 ATP
H
OH
Glucose-6-phosphate
2
Phosphoglucoisomerase
P
O CH2OH
H HO
OH
H
H
HO
Fructose-6-phosphate
CH2O
3
ATP
O C O
CHOH
1
Hexokinase
CH2O P
HH O H
OH H
OH
HO
2 Pi
2 NADH
+ 2 H+
P
ATP
6
Triose phosphate
dehydrogenase
2 NAD+
CH2OH
OH
HH
OH H
HO
OH
H OH
Glucose
Kinase
isomerase
Mutase
Aldolase
enolase
Dehydrogenase
Phosphofructokinase
ADP
O–
2
C
CHOH
CH2 O P
3-Phosphoglycerate
8
Phosphoglyceromutase
2
O–
C
O
H C O
P
CH2OH
2-Phosphoglycerate
9
Enolase
2H O
2
P
O CH2 O CH2 O
H HO
OH
H
HO
H
Fructose1, 6-bisphosphate
2
P
O–
C O
C O
4
Aldolase
Pyruvate kinase
2 ATP
5
P
O CH2
C O
CH2OH
Dihydroxyacetone
phosphate
Isomerase
H
2
C O
Figure 9.9 A
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O–
C O
CHOH
CH2 O P
Glyceraldehyde3-phosphate
P
CH2
Phosphoenolpyruvate
2 ADP
10
C O
Figure 9.8
CH3
Pyruvate
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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 9.3: The citric acid cycle completes
the energy-yielding oxidation of organic
molecules
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• The citric acid cycle
– Takes place in the matrix of the mitochondrion
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• Before citric acid cycle can begin
– Pyruvate must first be converted to acetyl CoA,
which links the cycle to glycolysis
CYTOSOL
MITOCHONDRION
NAD+
NADH
+ H+
O–
S
CoA
C
O
2
C
O
Pyruvate Oxidation
C
O
1
3
CH3
Pyruvate
Acetyle CoA
CO2
Coenzyme A
From Vit B
Transport protein
Figure 9.10
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CH3
• An overview of the citric acid cycle
= TCA (Tricarboxyl acid)
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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= Krebs Cycle
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
HO
Citrate
CH2
COO–
Isocitrate
COO–
H2O
CH
7
COO–
CH
CO2
Citric
acid
cycle
3
NAD+
COO–
Fumarate
HC
CH2
CoA SH
6
CoA SH
COO–
FAD
CH2
CH2
COO–
C O
Succinate
4
C O
COO–
CH2
5
CH2
FADH2
COO–
+ H+
a-Ketoglutarate
CH2
COO–
NADH
Pi
S
CoA
GTP GDP Succinyl
NAD+
CO2
NADH
+ H+
CoA
ADP
ATP
Figure 9.12
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A closer look at the citric acid cycle
Citric
Oxidative
acid phosphorylation
cycle
Glycolysis
2C
3C
pyruvate
S
CoA
C
O
CH3
NAD + CoA
NADH + CO2
Acetyl CoA
4C
O
NADH
+ H+
CoA SH
6C
C COO–
COO–
1
CH2
COO–
NAD+
8 Oxaloacetate
HO C
½ Glucose
4C
COO–
COO–
CH2
COO–
HO CH
H2O
CH2
CH2
2
HC COO–
COO–
Malate
Figure
CH2
HO
Citrate
9.12
Isocitrate
COO–
4C
CH
CO2
Citric
acid
cycle
7
3
NAD+
COO–
Fumarate
HC
CH2
CoA SH
CoA SH
COO–
FAD
CH2
CH2
COO–
C O
Succinate
4C
Pi
S
CoA
GTP GDP Succinyl
CoA
ADP
ATP
Figure 9.12
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4
C O
COO–
CH2
5
CH2
FADH2
COO–
4C
NAD+
NADH
+ H+
NADH
+ H+
a-Ketoglutarate
CH2
COO–
6
6C
COO–
COO–
H2O
CH
CO2
5C
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Energetics
DHase
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 9.4: During oxidative phosphorylation,
chemiosmosis couples electron transport to
ATP synthesis
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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
ATP
Substrate-level
phosphorylation
ATP
Oxidative
phosphorylation
• NADH and FADH2: Donate electrons to the electron
transport chain (ETC), which powers ATP synthesis
via oxidative phosphorylation
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The Pathway of Electron Transport
• In the ETC
NADH
50
– Electrons from
NADH and FADH2
lose energy in
several steps
FADH2
Free energy (G) relative to O2 (kcl/mol)
40
• At the end of the chain
Multiprotein
complexes
FAD
Fe•S
Fe•S
II
O
III
Cyt b
30
Fe•S
Cyt c1
IV
Cyt c
Cyt a
Cyt a3
20
10
– Electrons are passed to
oxygen, forming water
0
Figure 9.13
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I
FMN
2 H + + 12
O2
H2 O
Chemiosmosis: The Energy-Coupling Mechanism
• ATP synthase is the enzyme that actually
makes ATP
INTERMEMBRANE SPACE
H+
rotor
H+
H+
H+
H+
H+
H+
A
within
the
membrane spins
clockwise when
H+ flows past
it down the H+
gradient.
stator
A
anchored
in the membrane
holds the knob
stationary.
注意: H+& ATP的方向
rod
H+
A
(for “stalk”)
extending into
the knob also
spins, activating
catalytic sites in
the knob.
Three catalytic
sites in the
ADP
+
Pi
Figure 9.14
MITOCHONDRIAL MATRIX
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knob
ATP
stationary
join inorganic
Phosphate to ADP
to make ATP.
• At certain steps along the electron transport
chain
– Electron transfer causes protein complexes to
pump H+ from the mitochondrial matrix to the
intermembrane space. [逆反應; 與產生ATP時
的H+運送方向相反]
目的: resulting H+ gradient
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• The resulting H+ gradient
– Stores energy
– Is referred to as a proton-motive force
– Drives chemiosmosis in ATP synthase
• Chemiosmosis
– 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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Chemiosmosis & 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
IV
III
Inner
mitochondrial
membrane
ATP
synthase
II
FADH2
NADH+
Mitochondrial
matrix
H+
Cyt c
FAD+
NAD+
2 H+ + 1/2 O2
H2O
ADP +
ATP
Pi
(Carrying electrons
from, food)
H+
Chemiosmosis
Electron transport chain
Electron transport and pumping of protons (H+), ATP synthesis powered by the flow
which create an H+ gradient across the membrane Of H+ back across the membrane
Oxidative phosphorylation
Figure 9.15
NADH  3 ATP; FADH2  2 ATP
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An Accounting of ATP Production by Cellular
Respiration
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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Shuttles for transfer of reducing equivalents
from cytosol into mitochondria
補充 不考
DHAP/GA3P shuttle
Malate/Asp shuttle
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Glycolysis (aerobic)
Glucose +2ADP + 2Pi+ 2NAD+ 2 pyruvate +2ATP+2NADH+2H++2H2O
aerobic
Pyruvate Oxidation
1 Pyruvate + NAD+ + CoASH  1 Acetyl-CoA + 1 NADH + CO2
2 Pyruvate + 2 NAD+ + 2 CoASH  2 Acetyl-CoA + 2 NADH + 2 CO2
TCA
2 Acetyl-CoA + 4 H2O + 6 NAD+ + 2FAD + 2GDP + 2 Pi  2 CO2 + 6 NADH + 2 FADH2 + 2 CoA-SH + 2 GTP
Glycolysis 
2 ATP
2 NADH (2H)
Pyruvate Oxidation  TCA
2 (2x1) NADH
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2 (2x1) GTP/ATP
6 (2x3) NADH
2 (2x1) FADH2
Glycolysis (aerobic)
Glycolysis 
2 ATP
2 NADH (2H)
Pyruvate Oxidation  TCA
2 (2x1) NADH
2 (2x1) GTP/ATP
6 (2x3) NADH
2 (2x1) FADH2
NADH  3 ATP; FADH2  2 ATP EST & chemiosmosis
ATP 8
or (6) shuttle
6
2 + 18 + 4 = 38
= 36
• 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
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• Cellular respiration
– Relies on oxygen to produce ATP
• In the absence of oxygen [no cellular respiration]
– Cells can still produce ATP through
fermentation
• fermentation is a partial degradation of sugars that
occurs without oxygen
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• Glycolysis
– Can produce ATP with or without oxygen, in
aerobic or anaerobic conditions
• Fermentation consists of
– Glycolysis + reactions that regenerate NAD+, which can be
reused by glyocolysis
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Types of Fermentation
2 ADP + 2
P1
2 ATP
• alcohol fermentation
O–
C O
Glucose
Glycolysis
C O
3C
CH3
2 Pyruvate
2 NADH
2 NAD+
H
2 CO2
– Pyruvate is converted to
ethanol in two steps, one of
which releases CO2
H
H C OH
C O
CH3
2C
CH3
2 Ethanol
2 Acetaldehyde
(a) Alcohol fermentation
2 ADP + 2
Glucose
P1
• lactic acid fermentation
2 ATP
Glycolysis
O–
C O
C O
O
2
NAD+
2 NADH
3C
CH3
C O
3C
H
C OH
CH3
2 Lactate
Figure 9.17
(b) Lactic acid fermentation
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– Pyruvate is reduced directly
to NADH to form lactate as a
waste product
• Anaerobic metabolism
Electrons
carried
via NADH 2
3x2
2x2
Citric
acid
cycle
Glycolsis
Pyruvate
Glucose
Cytosol
lactate
Or
ethanol
Oxidative
phosphorylation:
electron
transport and
chemiosmosis
Mitochondrion
2 ATP
Figure 9.6
Electrons carried
via NADH and
FADH2
Substrate-level
phosphorylation
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1x2 ATP
Substrate-level
phosphorylation
32-34 ATP
Oxidative
phosphorylation
• 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
Summaries of Glycolysis
1. anaerobic
Glucose -> 2 Lactate + 2 ATP (lactic acid fermentation)
Glucose -> 2 Ethanol + 2 ATP (alcoholic fermentation)
2. aerobic
Glucose -> 2 Pyruvate + 2ATP + 2NADH (aerobic subtotal)
註: 2 NADH -> 6 ATP (aerobic conversion: 氧化磷酸化)
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Fermentation and Cellular Respiration Compared
• 相同點
Use glycolysis to oxidize glucose and other
organic fuels to pyruvate
•
相異點
1.Differ in their final electron acceptor
Fermentation by acetylaldehyde (ethanol ferment.); by
pyruvate (lactate ferment.)
Cellular Respiration by O2
2.Cellular respiration produces more ATP
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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
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
Fatty
acids
Glycolysis
Glucose
Glyceraldehyde-3- P
NH3
Pyruvate
Acetyl CoA
Citric
acid
cycle
Figure 9.19
Oxidative
phosphorylation
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b-oxidation
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 (e.g., Phosphofructokinase) at key
points in glycolysis and the citric acid cycle
Allosteric regulation (see glossary)
The binding of a molecule to a protein that affects the function of the
protein at a different site.
補充圖
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• 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
Oxidative
phosphorylation
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• ATP  AMP + ppi
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