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Chapter 18
Oxidative phosphorylation
Mitochondria, stained green, from a network
inside a fibroblast cell. Mitochondria oxidize
carbon fuel to form cellular energy in the form
of ATP.
Outline
18.1 Eukaryotic Oxidative Phosphorylation Takes
Place in Mitochondria
18.2 Oxidative phosphorylation Depends on Electron
Transfer
18.3 The Respiratory Chain Consists of Four
Complexes: Three Proton Pumps and a physical
Link to the Citric Acid Cycle
18.4 A Protein Gradient Powers the Synthesis of ATP
18.5 Many Shuttles Allow Movement Across the
Mitochondrial Membrane
18.6 The Regulation of Cellular Respiration Is
Governed Primarily by the Need for ATP
2
7okg male  need 8400kJ/day need 83kg ATP
recycle ATP about 300 times/day
Electron-transport chain (respiratory chain): electron flow
NADH + ½ O2 + H+  H2O + NAD+
The proton pumps from mitochondria matrix into the
intermembrane space
pH gradient
proton-motive force
TCA
CO2
Cellular respiration
ADP + Pi + H+  ATP + H2O
Fig 18.1 Overview of oxidative phosphorylation
3
18.1 Eukaryotic Oxidative Phosphorylation
Takes Place in Mitochondria
•Mitochondria are bounded by a double membrane
– Oval shaped, about 2μm in length an 0.5 μm in diameter
– Two membrane system:
• Outer membrane
– Quite permeable to most small molecules and ions
– Contains mitochondrial porin (30-35kd pore-forming
protein; VDAC; voltage dependent anion channel)
» Regulate flux of metabolites, usually anions, such as
phosphate, chloride, organic anions, and adenine nucleotides
• Highly folded inner membrane -- cristae
• Intermembrane space
• Matrix
Fig 18.2 Electron micrograph
(A) and diagram (B) of a
mitochondria.
(A)
4
(B)
•Mitochondria are bounded by a double membrane
–Oval shaped, about 2μm in length an 0.5 μm in diameter
–Two membrane system:
• Outer membrane
• Highly folded inner membrane -- cristae
– Human contain an estimated 14,000m2 of inner membrane
– Oxidative phosphorylation
– Impermeable to nearly all ions and polar molecules
– A large family of transporters shuttles metabolites such as
ATP, pyruvate, and citrate across the inner membrane
– The two faces of this membrane
» Matrix side (N sides): membrane potential is negative
» Cytoplasmic side (P sides): membrane potential is positive
• Intermembrane space
• Matrix
– TCA cycle
– Fatty acid oxidation
5
Biochemical anatomy
of a mitochondrion
• 一個肝臟粒線體的內膜至少有超過
10,000 電子傳遞系統 (electrontransfer systems)及 ATP 合成酶
synthase
• 而心臟的粒線體具較多的cristae
並超過3倍肝臟內膜的區域，具有
更多的電子傳遞系統
• 無脊椎動物、植物及微小脊椎動物
的粒線體與脊椎動物相似，惟其大
小、形狀及內膜內凹程度各有不同
(MW<5000)
specific transporters
6
•In prokaryotes
–The electron-driven proton pumps and ATPsynthesizing complex are located in the cytoplasmic
membrane, the inner of two membranes
–Outer membrane of bacteria is permeable to most
small metabolites (porins)
Proton gradient +
Membrane potential
電子傳遞導致質子被送
出穿越粒線體內膜
Fig 20.1 A proton gradient is established across the inner mitochondrial 7
membrane as a result of electron transport
Mitochondria are the result of an endosymbiotic
內共生 event
•Mitochondria are semiautomous
organelles –endosymbiotic relation with
the host cell
–Contain DNA
•Encodes a variety of different proteins and
RNAs
•Circular or linear form DNA
•The genomes range broadly in size across
species
•Human mitochondria DNA 16569bp,
encodes 13 respiratory-chain proteins,
rRNAs, tRNAs
8
Fig 18.3 sizes of mitochondria
genomes.
Universal Electron Acceptors
•氧化磷酸化反應起源於電子進入呼吸鏈中
–靠的是去氫酶(dehydrogenase)的作用
–主要的電子接受器(electron acceptor) 為nicotinamide
nucleotide (NAD+ or NADP +)或flavin nucleotide (FMN or
FAD)
•nicotinamide nucleotide-linked dehydrogenase
– Reduced substrate + NAD+ 
Oxidized substrate + NADH + H+
– Reduced substrate + NADP+ 
Oxidized substrate + NADPH + H+
– 每次移走兩個氫原子
•Flavoproteins
– 可接受1或2個電子 (semiquinone form or FADH2, FMNH2)
9
10
18.2 Oxidative phosphorylation Depends
on Electron Transfer
•In oxidative phosphorylation, the electron-transfer
potential of NADH or FADH2 is converted into
phosphoryl-transfer potential of ATP
–A useful way to look at electron transport is to
consider the change in free energy associated with
the movement of electrons from one carrier to
another (自由能的改變與電子的移動)
•reduction potential (oxidation-reduction potiential)
– A carrier of high reduction potential will tend to be
reduced if it is paired with a carrier of lower reduction
potential (較高還原電位者被還原;較高還原電位者會得
到電子)
11
依電流方向得知還原電位的高低
Ethanol acetaldehyde + 2H++ 2eEo’=-0.197V
Fumarate + 2H++ 2e- succinate
Eo’=+0.031V
較高還原電位
Fig 20.3 Experimental apparatus used to measure the standard reduction potential of the
indicated redox couples: (a) the ethanol/acetaldehyde couple; (b) the
fumarate/succinate couple
12
Standard biological
voltage
Base on
1M, pH 7 at 25oC
(standard state)
13
14
NAD+ + 2H+ +2e-  NADH + H+ Eo’=-0.320V
During redox reaction:
NADH + H+  NAD+ + 2H+ +2e- Eo’=0.320V
½ O2 + 2H+ +2e-  H2O
Eo’=0.816V
NADH + ½ O2 + H+  NAD+ + H2O Eo’ =1.136V
Go=-nFEo’
Go: free energy change in the standard state
n: the number mole of electron transferred
F: Faraday’s constant (96.485kJV-1mol-1)
Eo’: the voltage for the two half reactions
When Eo’ is positive Go is negative
Go=-(2)(96.485kJV-1mol-1)(1.136V)
= -219kJ mol-1
NADH passes its electrons along a chain that eventually lead to
oxygen, but it does not reduce oxygen directly
15
18.3 The Respiratory Chain Consists of Four
Complexes: Three Proton Pumps and a
physical Link to the Citric Acid Cycle
•Four separate respiratory complexes can be isolated from
the inner mitochondria membrane –by fractionation 在粒
線體內膜可分離出四種呼吸複合體
– Multienzyme systems 屬多酵素的系統 (super molecule
complex termed the respirasome)
•Complex I: NADH-Q oxidoreductase 氧化還原酶
•Complex II: succinate-Q reductase
– Does not pump protons
•Complex III: Q-cytochrome c oxidoreductase
•Complex IV: cytochrome c oxidase 氧化酶
– Each of the respiratory complexes can carry out the
reactions of a portion of the electron transport chain 每個呼
吸複合體都可完成電子傳遞鏈中一部份的反應
16
17
Fig 18.6 Components of the electron-transport chain
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Fig 20-6 The electron transport chain, showing the respiratory complexes
19
Two special electron carriers ferry the electrons
from complex to the next
•Coenzyme Q (Q) : ubiquinone (泛醌)
–Hydrophobic quinone
–Diffuses rapidly within the inner membrane
–Electrons are carried from NADH-Q oxireductase
to Q-cytochrome c oxidoreductase
–FADH2 generated by the TCA cycle are transferred
to ubiquinone to the Q-cytochrome
–With a long tail consisting of five carbon isoprene
units (contain 10 units  coenzyme Q10)
–Three oxidation states: Q, QH., QH2
•Electron-transfer reactions are coupled to proton
binding and release
•Cytochrome C
20
Fig 18.7 Oxidation states of quinones
21
Two special electron carriers ferry the electrons
from complex to the next
•Coenzyme Q (Q) : ubiquinone (泛醌)
•Cytochrome C
–Small soluble protein
–Shuttles electrons from Q-cytochrome c oxidoreductase
to cytochrome c oxidase
–Catalyzes the reduction of O2
22
The high potential electrons of NADH enter the
respiratory chain at NADH-Q oxidoreductase
Complex I: NADH-CoQ oxidoreductase 氧化還原酶
• Catalyzes the first steps of electron transport
• Transfer of electrons from NADH to coenzyme Q (CoQ)
• L-shaped, with horizontal arm lying in the membrane and a
vertical arm projects into the matrix
– An enormous enzyme consisting ~46 polypeptides
– Proteins contain an iron-sulfur clusters
– Flavoprotein that oxidizes NADH
» Has a flavin coenzyme  flavin mononucleotide (FMN)
23
Fig 18.8 Oxidation states of flavins
•Fe-S clusters in iron-sulfur proteins (nonheme iron
proteins)
–NADH-Q oxidoreductase contain both 2Fe-2S and 4Fe-4S
clusters
–Iron ions in these Fe-S complexes cycle between Fe2+
(reduced) and Fe3+ (oxidized) state.
–Undergo oxidation-reduction reactions without
releasing or binding protons.
2Fe-2S cluster contains 2 irons,
2 sulfides and 4 cys.
Single iron ion bound by 4 cys.
Fig 18.9 Iron-sulfur clusters
4Fe-4S cluster contains244 irons
4 sulfide ions and 4 cys.
First step
All the redox reactions take place in the
extramembranous part of the enzyme
•Electrons are passed from NADH to FMN
NADH + H+ + E-FMN  NAD+ + E-FMNH2
E-FMN: the flavin is covalently bonded to the enzyme
Second step
•The reduced flavoprotein is reoxidized
•The oxidized form of the iron-sulfur protein is reduced
E-FMNH2 + 2Fe-Soxidized  E-FMN + 2Fe-Sreduced + 2H+
Third step
•The reduced iron-sulfur protein then donates its electron to
coenzyme Q (CoQ; ubiquinone 泛醌)
Reduced to CoQH2 (還原成CoQH2)
2Fe-Sreduced + CoQ +2H+  2Fe-Soxidized + CoQH2
Over all equation 反應總方程式
NADH + 5H+matrix + CoQ  NAD + + CoQ H2 +4H+cytoplasm
25
Pump 4 hydrogen ions out of the matrix
Q takes up 2 protons and 2
electrons from the matrix and
reduced to QH2
Fig 18.10 Coupled electron-proton transfer reactions
through NADH-Q oxidoreductase
26
Ubiquinol is the entry point for electrons from
FADH2 of plavoproteins
•FADH2 enter the electron-transport chain at the complex II
(succinate-Q reductase complex)
–Integral membrane protein of the inner membrane
•FADH2 electrons are transferred to Fe-S centers
•Then finally to Q to form QH2
•Does not pump protons
•Less ATP is formed from the oxidation of FADH2 than from
NADH
•Two other enzymes, glycerol phosphate dehydrogenase and
fatty acyl CoA dehydrogenase transfer high potential
electrons from FADH2 to Q to form ubiquinol
–Also do not pump protons
27
Electrons flow from ubiquinol to cytochrome c
through Q-cytochrome c oxidoreductase
•Electrons from QH2 to cytochrome c by complex III (Qcytochrome c oxidoreductase; cytochrome reductase)
–The overall reaction:
QH2 + 2cyt cox+ 2H+matrix  Q + 2cyt cred + 4H+cytoplasm
•The components of Q- cytochrome c oxidoreductase
–Three hemes (iron-protoporphyrin IX)
» Cytochrome b (Cytochrome bH and bL (low for low affinity))
» Cytochrome c1
» The iron ions of a cytochrome alternates between a reduced
ferrous (+2) state and a oxidized ferric (+3)state
–Several iron-sulfur proteins – 2Fe-2S center (Rieske center)
» One of the irons ions is coordinated by two histidine residues
» Stabilized the center
– Cytochromes can carry electrons, but no hydrogens
28
Fig 18.11 Structure of Q-cytochrome c oxidoreductase (cytochrome bc1) 29
The Q cycle funnels electrons from a twoelectron carrier to a one-electron carrier and
pumps protons
•QH2 passes two electrons to complex III, but the electrons
acceptor cytochrome c can accept one electron
Q cycle
–Two QH2 molecules bind to the complex consecutively, each
giving up two electrons and two H+
Q0: first Q binding site
Qi: second Q binding site
Complex III
Complex III
Fig 18.12 Q-cycle
30
整個反應釋出4的氫離子
FIGURE 19-12 The Q cycle, shown in two stages.
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•Q cycle
– One electron is passed from reduced CoQ to the iron-sulfur
clusters to cytochrome c1  semiquinone
CoQH2 + Cyt c1 (oxidized) 
Cyt c1 (reduced) + CoQ- +2H+
– Semiquinone in a cycle process  two b cytochromes are
reduced and oxidized
– A second molecule of CoQ transfer a second electron to
cytochrome c1 and to the cytochrome c
electrons to be transferred one at a time from coenzyme Q to
cytochrome C1 由CoQ每次傳送一個電子到細胞色素c1
Over all equation
2QH2 + Q + 2 cyt cox + 2H+matrix  QH2 +2 Q + 2 cyt cred + 4H+cytoplasm
32
Cytochrome c oxidase catalyzes the reduction of
molecular oxygen to water
Complex IV: cytochrome c oxidase 細胞色素c氧化酶
• The transfer of electrons from cytochrome c to oxygen
4cyt c [Fe(II)] + 8H+matrix + O2  4cyt c [Fe(III)] + 2H2O + 4H+cytoplasm
• The components of this complex
–Integral protein of the inner mitochondrial membrane
–Three Cu2+ (Two copper center; CuA/CuA and CuB) Cu+  Cu2+
–Two heme A groups
»Formyl group replaces methyl groups
»C17 replaces vinyl group
»Not covalently attached protein
»heme a, heme a3
33
O22Fig 18.15 peroxide bridge
Electrons stop at CuB and heme a3
Reduced state
Oxygen binding
4cyt c [Fe(II)] + 8H+matrix + O2 
4cyt c [Fe(III)] + 2H2O + 4H+cytoplasm
Fig 18.14 cytochrome c oxidase mechanism
34
FADH2
Fig 18.17 The electron-transport chain
35
Toxic derivatives of molecular oxygen such as a
superoxide radical are scavenged by protect enzyme
O2
e-
e-
O2- .
Superoxide
ion
O22-
Reactive oxygen species (ROS)
Peroxide
•the transfer of a single electron to O2 forms superoxide
anion, where the transfer of two electrons yields peroxide.
cytochrome c oxidase hold O2 tightly between Fe and Cu ions.
superoxide dismutase
– A Mg-containg enzyme located in mitochondria
– A Cu- and Zn-dependent cytoplasmic form
Superoxide
dismutase
-.
+
O2 + H2O2
O2 + 2H
2 H2O2
catalase
O2 + 2H2O
36
•Glutathione peroxidase also plays a role in scavenging H2O2
•Antioxidant vitamins: vitamins E and C
• Vitamine E (lipophilic) is especially useful in protecting
membranes from lipid peroxidation
Fig 18.18 superoxide dismutase mechanism
37
動脈粥狀硬化
肺氣腫 ; 支氣管炎
裘馨氏肌肉失養症
唐氏綜合症
38
18.4 A Protein Gradient Powers the
Synthesis of ATP
•In electron transport
NADH + ½ O2 + H+  H2O + NAD +
ΔGo’ =-220.1 kJmol-1
•How this process is coupled to the synthesis of ATP
ADP + Pi +H+  ATP + H2O
ΔGo’ =+30.5 kJmol-1
•Mitochondrial ATPase or F1F0 ATPase or Complex V
39
The Mechanism of
Coupling in Oxidative
phosphorylation
Membrane potential 0.14V
Fig 18.22 chemiosmotic hypothesis
•In 1961, Peter Mitchell: The chemiosmotic hypothesis
–Electron transport and ATP synthesis are coupled by a
proton gradient across the inner mitochondrial membrane
•Electron transfer through the respiratory chain
pumping of protons from the matrix to the cytoplasmic side
of the inner mitochondrial membrane
– [H+] is lower in the matrix
•Protons them flow back into the matrix
– Drive the synthesis of ATP by ATP synthase
•The energy-rich unequal distribution of protons is called
the proton-motive force power the synthesis of ATP
– Chemical gradient: pH gradient
– Charge gradient
40
Proton-motive force (Δp) = chemical gradient (ΔpH) +
charge gradient (Δψ)
The respiratory chain and ATP
synthase are biochemically
separate systems, linked only by a
proton-motive force
•NADH oxidation is coupled to
ATP synthesis are:
–Electron transport generates
a proton-motive force
–ATP synthesis by ATP
synthase can be powered by a
proton-motive force
How??
Fig 18.23 Testing the Chemiosmotic hypothesis
41
ATP synthase is composed of a protonconducting unit and a catalytic unit
•ATP synthase
–Large, complex enzyme
–Two components:
•F0 subunits
– Hydrophobic segment that span in the inner
mitochondrial membrane
– Contains the proton channel of the complex
– Consists of a ring comprising from 10-14 c subunits that
are embedded in the membrane
– A single a subunit binds to the outside of the ring
•F1 subunits
– 85-Å-diameter, protrudes into the matrix
– Catalytic activity of the synthase
– Consists of 5 types of polypeptide chains (α3, β3, γ, δ, ε)
» The α and β subunits arranged in a hexameric ring
» β subunits participate directly in catalysis
» γ subunit with a long helical coiled coil that extends into
the α3β3 hexamer (make β subunits unequivalent)
Fig 18.24 Structure of
ATP synthase
•F0 and F1 are connected by the central γε unit and by
42
an exterior column (a, 2b and δ)
Proton flow through ATP synthase leads to the
release of tightly bound ATP: the binding-change
mechanism
Fig 18.25 ATP-synthesis mechanism
•ADP and ATP complex with Mg2+
•Isotopic exchange experiment:
–Enzyme-bound ATP forms readily in the absence of a
proton-motive force
Fig 18.26 ATP forms without a proton-motive force but is not released
–The role of the proton gradient is not to form ATP but to
release it from the synthase
43
•Three β subunits are components of the F1 moiety of
the ATPase
–Three active sites on the enzyme
–Each performs different functions
–The proton-motive force causes the three active sites to
sequentially change functions
•The enzyme consists:
–The moving unit – rotor
•c ring and the γε stalk
–The stationary unit – stator
•Remainder of the molecule
44
•Binding-change Mechanism for proton-driven ATP synthesis
–A β subunit performs each of three sequential steps in the
synthesis of ATP by change conformation
•ADP and Pi binding
•ATP synthesis
•ATP release
–Loose conformation (L)
•Binds ADP and Pi
–Tight conformation (T)
•Binds ATP with great avidity
•catalytically active
•Convert bound ADP and Pi into ATP
–Open form (O)
•low affinity for substrate
•Bind or release adenine nucleotide
45
Fig 18.27 ATP synthase nucleotidebinding site are not equivalent
•The rotation of the γ subunit drives the interconversion
of these three forms
–ATP can be synthesis and released by driving the rotation
of the γ subunit
Fig 18.28 Binding -change mechanism for ATP synthase
46
How does proton flow through F0 drive the
rotation of the γ subunit?
•Dependent on the a and c subunits of F0
–Stationary a subunits directly abuts membrane-spanning
ring formed by 10-14 c subunits
–Subunit a includes two hydrophilic half-channels
•Directly interacts with one c subunit
•Protons can enter and pass partway but not complete
through the membrane
–c subunits
•A pair of α helix (span the membrane)
•An aspartic acid in the middle
Allow protons to enter
47
Fig 18.30 components of the proton-conducting unit of ATP synthesis
•In proton rich environment
– A proton will enter a channel
(cytoplasmic half channel)
– Bind the aspartate residue of c subunits
Fig 18.32 proton path
through the membrane
(c subunit)
Fig 18.31 proton motion across the membrane drives rotation of the c ring
48
How does the rotation of the c ring lead to the
synthesis of ATP?
•The c subunit is tightly linked to the γ and ε subunits
–As the c ring turn
–The γ and ε subunits are turned inside the α3β3 hexamer of F1
•Each 360-degree rotation of the γ subunit
–The synthesis and release of three molecules of ATP
–If there 10 c subunits in the ring
•Transfer 10 protons
•Each ATP generated requires 10/ 3 = 3.3 protons
•The true value may differ
•NADH pump enough protons to generate 2.5 molecules ATP;
FADH2 yield 1.5 molecules of ATP
49
FIGURE 19-19 Chemiosmotic model.
•The inner mitochondrial membrane is impermeable to protons
•protons can reenter the matrix only through proton-specific channels
(Fo).
• The proton-motive force that drives protons back into the matrix provides
the energy for ATP synthesis, catalyzed by the F1 complex associated with
50
Fo.
18.5 Many Shuttles Allow Movement
Across the Mitochondrial Membrane
Electrons from cytoplasmic NADH enter
mitochondria by shuttles
–The inner mitochondrial membrane is impermeable
to NADH and NAD+
–Using
•Glycerol 3-phosphate shuttle
•Malate-aspartate shuttle
51
Glycerol 3-phosphate shuttle
Transfer a pair of electrons from NADH to
dihydroxyacetone phosphate to form
glycerol 3-phosphate
From glycolysis
(move into the mitochondria)
(membrane bound isozyme)
Outer surface of the inner
mitochondrial membrane
• Cytoplasmic NADH transported by glycerol 3-phosphate shuttle
 1.5 molecules of ATP are formed
52
• especially in muscle to sustain high rate of oxidative phosphorylation
Malate-aspartate shuttle
•In heart and liver
From glycolysis
Malate dehydrogenase
Aspartate aminotransferase
• Cytoplasmic NADH transported by malate-aspartate shuttle
53
 2.5 molecules of ATP are formed
The entry of ADP into mitochondria is coupled to
the exit of ATP by ATP-ADP translocase
•ATP and ADP do not diffuse free across the inner
mitochondrial membrane
–Specific transport protein, ATP-ADP translocase
•Highly abundant (15% protein of the inner membrane)
•30kd translocase contains a single nucleotide-binding site
– Face the matrix and the cytoplasmic side of the membrane
–ADP enters the mitochondrial matrix only if ATP exits
ADP3-cytoplasm + ATP4-matrix  ADP3-matrix + ATP4-cytoplasm
–ADP and ATP bind to the translocase wothout Mg2+
–ATP transport out of the matrix and ADP transport into
the matrix
•ATP has one more negative charge
•Membrane potential
54
Fig 18.36 Mechanism of mitochondrial ATP-ADP translocase
55
Synthasome: ATP-ADP translocase + phosphate carrier + ATP synthase
Contain 3 tandem repeats of a 100 a.a. module that come
together to form a binding site
Fig 18.38 mitochondrial transporters
More than 40 such carriers are encoded in the human genome
56
18.6 The Regulation of Cellular Respiration Is
Governed Primarily by the Need for ATP
57
The rate of oxidative phosphorylation id
determined by the need for ATP
•When ADP concentration rises, the rate of oxidative
phosphorylation increase to meet the ATP needs
•Respiratory control or acceptor control
–Electron do not flow from fuel molecules to O2 unless
ATP needs to by synthesis
58
Regulated uncoupling leads to the generation of heat
•Some organisms possess the ability to uncouple oxidative
phosphorylation from ATP synthesis to generate heat
–Maintain body temperature in hibernating animals, in some
newborn animals, and adult mammals
–The uncoupling is in brown adipose tissue (BAT)
•Specialized tissue for the process of nonshivering thermogenesis
(指為因應環境溫度改變，增加能量消耗的產熱反應; 非顫抖產熱反應)
•Very rich in mitochondria called brown fat mitochondria
•The combination of the greenished-colored cytochromed in the
mitochondria and the red hemoglobin
•Mitochondria contains a large amount of uncoupling protein
(UCP-1) or thermogenin (a dimer of 33kd that resemble ATP-ADP
translocase
褐色脂肪組織於新鮮活體狀態呈褐色，其脂肪細胞內儲存多量之小型油滴，細胞核呈
橢圓形且細胞質內富含粒腺體。褐色脂肪細胞在脂紡氧化之過程，不形成 ATP 而將所
含之能量以熱能形式釋放，提供動物體溫與熱能之需求，在小型哺乳動物之體溫維持
上 與動物冬眠之甦醒時，扮演極重要之角色。人類之褐色脂肪組織從出生後到生命之
59
前十 年內會逐漸減少，而白色脂肪組織則相反，所以成為成人之脂肪組織。
Fig 18.38 Action of an uncoupling protein
60
Oxidative phosphorylation can be
inhibited at many stages
1.Inhibition of the electron-transport chain
•Block the transfer of electrons from the
flavoprotein NADH reductase to coenzyme Q
•Barbiturates巴比妥鹽藥物
– Amytal
– Rotenone
•The blockage occur involving the electron transfer
of b cytochromes, coenzyme Q, and cytochrome c1
– Antimycin A抗黴素A
» myxothiazol
» UHDBT
•The blockage occur involving the electron transfer
from cytochromes aa3 complex to oxygen
– Cyanide (CN-)
– Azide (N3-)
– Carbon monoxide (CO)
61
2. Inhibition of ATP synthase
–Oligomycin寡黴素
•Antifungal agent
•Prevent the influx of protons through ATP synthase
3. Uncoupling electron from ATP synthesis
–2,4-dinitrophenol (DNP) 2,4-二硝酚
•Electron transport from NADH2 proceeds in a normal fashion
•ATP is not form by mitochondrial membrane
4. Inhibition of ATP export
–Atractyloside
•Binds to the translocase when its nucleotide site face the
cytoplasm
–bongkrekic acid
•Binds when this site faces the matrix
62