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Fundamentals of Biochemistry
Fourth Edition
Chapter 18 Electron Transport and Oxidative Phosphorylation
Donald Voet • Judith G. Voet • Charlotte W. Pratt
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The Structure of the Mitochondrion A Few Aspects of Communication Between Cytosol and
Mitochondrion Overview of Electron Transport in Mito Membrane
Intro to Some New Players – Co-Enzyme Q, Fe-S proteins and Cytochromes
Organization of Electron Transport Generation of Proton Motive Force by Arrangement of e-
carriers ATP synthesis – ATPase is a machine
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Overview: Oxidative Fuel Metabolism
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Overview: Oxidative Fuel Metabolism
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Overview: Oxidative Fuel Metabolism
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Chapter 18 The Mitochondrion
Key Concepts 18.1 • A highly folded, protein-rich inner membrane separates the
mitochondrial matrix from the outer membrane.
• Transport proteins are required to import reducing
equivalents, ADP, and Pi into the mitochondria.
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Animal Mitochondrion
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Mitochondrion Cutaway Diagram
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Mitochondrial Cristae
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Inner Membrane Is Rich In Proteins
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Glycerophosphate Shuttle
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Bovine ATP-ADP Translocator: Ligand Induced Conformational Changes
Bovine heart ATP-ADP translocator PDBid 2C3E
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Bovine ATP-ADP Translocator: Positively Charged Cavity Binds ATP
Bovine heart ATP-ADP translocator PDBid 2C3E
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Chapter 18 The Mitochondrion
Checkpoint 18.1 • Draw a simple diagram of a mitochondrion and idenAfy its
structural features.
• Describe how shuBle systems transport reducing
equivalents into the mitochondria.
• Explain how the free energy of the proton gradient drives
the transport of ATP, ADP, and Pi.
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Chapter 18 Electron Transport
Key Concepts 18.2 • The free energy of electron transport from NADH to O
2 can
drive the synthesis of approximately 2.5 ATP.
• Electron carriers are arranged in the mitochondrial
membrane so that electrons travel from Complexes I and II
via coenzyme Q to Complex III, and from there via
cytochrome c to Complex IV. • The L-shaped Complex I transfers electrons from NADH to
CoQ via a series of iron–sulfur clusters and translocates four
protons to the intermembrane space.
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Chapter 18 Electron Transport
Key Concepts 18.2 • Complex II transfers electrons from succinate to the CoQ
pool but does not contribute to the transmembrane proton
gradient.
• Electrons from Complex III are transferred to cytochrome c and two protons are translocated during the operaAon of the Q cycle in Complex III.
• Complex IV accepts electrons from cytochrome c to reduce O
2 to H
2 O and translocates four protons for every two
electrons transferred.
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Overview of Electron Transport
air
vectory arrangement of alternating carries the electron and proton or the electron only
air
damp on the other side
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Inhibitors Reveal Electron-Transport Chain Sequence of Events
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Reduction Potentials of ETC Components
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Reduction Potentials of ETC Components
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Mitochondrial Electron-Transport Chain
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Iron-Sulfur Clusters
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Complex I
Complex I from Thermus thermophilus PDBid 3M9S
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Oxidation States of FMN & CoQ
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Oxidation States of FMN & CoQ
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Peripheral Arm of Complex I
Thermus thermophilus PDBid 2FUG
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Redox Active Prosthetic Groups Peripheral Arm of Complex I
Thermus thermophilus PDBid 2FUG
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Complex II
Chicken Complex II PDBid 1YQ3
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Box 18-1: Cytochromes are Electron -Transport Heme Proteins
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Box 18-1: Cytochromes are Electron -Transport Heme Proteins
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Complex III
Yeast Complex III PDBid 1KYO
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The Q Cycle
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Stigmatellin Blocks Qo Site
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Cytochrome c
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Complex IV
Bovine heart cytochrome c oxidase homodimer PDBid 1V54
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Redox Centers of Complex IV
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Proposed Reaction Sequence for Complex IV
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Chapter 18 Electron Transport
Checkpoint 18.2 • Describe the route followed by electrons from glucose to O
2 .
• Write the net equaAon for electron transfer from NADH to
O 2 .
• Assuming 100% efficiency, calculate the maximum amount of
ATP that could be synthesized as a result.
• For each of the electron-transport complexes, write the
relevant redox half-reacAons.
• PosiAon the four electron-transport complexes on a graph
showing their relaAve reducAon potenAals, and indicate the
path of electron flow.
• How did inhibitors reveal the order of electron transport?
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Chapter 18 Oxidative Phosphorylation
Key Concepts 18.3 • The chemiosmoAc theory explains how a proton gradient
links electron transport to ATP synthesis.
• ATP synthase consists of an F1 component that catalyzes
ATP synthesis by a binding change mechanism.
• The F0 component of ATP synthase includes a c-ring whose rotaAon is driven by the dissipaAon of the proton gradient
and drives conformaAonal changes in the F1 component.
• For every two electrons that enter the electron-transport
chain as NADH and reduce one oxygen atom, approximately
2.5 ATP molecules are produced, giving a P/O raAo of 2.5.
• Agents that dissipate the proton gradient can uncouple
electron transport and ATP synthesis.
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Coupling of Electron Transport and ATP Synthesis
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Box 18-3: Bacterial Electron Transport & Oxidative Phosphorylation
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Box 18-3: Bacterial Electron Transport & Oxidative Phosphorylation
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F1 Components of ATP Synthase Protrude From Mitochondrial Cristae
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F1 Component of ATP Synthase
Bovine F1-ATP synthase PDBid 1E79
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Model of F1F0-ATPase
F1F0-ATPase PDBids 1JNV, 2A7U, and 1B9U
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Binding Change Mechanism for ATP Synthase
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Inner Sleeve of F1 α3β3 Assembly Interacts with γ-Subunit
F1 α3β3 PDBid 1BMF
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Model of F1F0-ATPase
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pH-Dependent Conformational Change of c Subunit of F1F0-ATPase
C subunit of E. coli F1F0-ATPase PDBid 1COV
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ATP-Dependent Rotation of c-Ring From F1F0-ATPase
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ATP-Dependent Rotation of c-Ring From F1F0-ATPase
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Nonphysiological Electron Donor Yields ATP
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Oxidative Phosphorylation Can Be Uncoupled From Electron Transport
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Chapter 18 Oxidative Phosphorylation
Checkpoint 18.3 • Summarize the chemiosmoAc theory.
• Explain why an intact, impermeable mitochondrial membrane
is essenAal for ATP synthesis.
• Describe the overall structure of the F1 and F0 components of
ATP synthase. Which parts move? Which are staAonary? Which
are mostly staAonary but undergo conformaAonal changes?
• Summarize the steps of the binding change mechanism.
• Describe how protons move from the intermembrane space
into the matrix. How is proton translocaAon linked to ATP
synthesis?
• Explain why the P/O raAo for a given substrate is not
necessarily an integer.
• Explain how oxidaAve phosphorylaAon is linked to electron
transport and how the two processes can be uncoupled.
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Chapter 18 Control of Oxidative Metabolism
Key Concepts 18.4 • The rate of oxidaAve phosphorylaAon is coordinated with
the cell s other oxidaAve pathways.
• Although aerobic metabolism is efficient, it leads to the
producAon of reacAve oxygen species.
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Box 18-4: Uncoupling in Brown Adipose Tissue Generates Heat
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Coordinated Control of Glycolysis and the Citric Acid Cycle
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Coordinated Control of Glycolysis and the Citric Acid Cycle
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Coordinated Control of Glycolysis and the Citric Acid Cycle
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Box 18-5: Oxygen Deprivation in Heart Attack & Stroke
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Electrostatic Effects in SOD
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Proc Natl Acad Sci U S A. 1991 Jun 1; 88(11): 4870–4873. Mitochondrial respiration in hummingbird flight muscles. R K Suarez, J R Lighton, G S Brown, and O Mathieu-Costello Abstract Respiration rates of muscle mitochondria in flying hummingbirds range from 7 to 10 ml of O2 per cm3 of mitochondria per min, which is about 2 times higher than the range obtained in the locomotory muscles of mammals running at their maximum aerobic capacities (VO2max). Capillary volume density is higher in hummingbird flight muscles than in mammalian skeletal muscles. Mitochondria occupy approximately 35% of fiber volume in hummingbird flight muscles and cluster beneath the sarcolemmal membrane adjacent to capillaries to a greater extent than in mammalian muscles. Measurements of protein content, citrate synthase activity, and respiratory rates in vitro per unit mitochondrial volume reveal no significant differences between hummingbird and mammalian skeletal muscle mitochondria. However, inner membrane surface areas per unit mitochondrial volume [Sv(im,m)] are higher than those in mammalian muscle. We propose that both mitochondrial volume densities and Sv(im,m) are near their maximum theoretical limits in hummingbirds and that higher rates of mitochondrial respiration than those observed in mammals are achieved in vivo as a result of higher capacities for O2 delivery and substrate catabolism.
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Mitochondrial responses to prolonged anoxia in brain of red-eared slider turtles Matthew E. Pamenter, Crisostomo R. Gomez, Jeffrey G. Richards, William K. Milsom Published 13 January 2016.DOI: 10.1098/rsbl.2015.0797 /.panel-row-wrapper. “Biology Letters” Mitochondria are central to aerobic energy production and play a key role in neuronal signalling. During anoxia, however, the mitochondria of most vertebrates initiate deleterious cell death cascades. Nonetheless, a handful of vertebrate species, including some freshwater turtles, are remarkably tolerant of low oxygen environments and survive months of anoxia without apparent damage to brain tissue. This tolerance suggests that mitochondria in the brains of such species are adapted to withstand prolonged anoxia, but little is known about potential neuroprotective responses. In this study, we address such mechanisms by comparing mitochondrial function between brain tissues isolated from cold-acclimated red-eared slider turtles (Trachemys scripta elegans) exposed to two weeks of either normoxia or anoxia. We found that brain mitochondria from anoxia -acclimated turtles exhibited a unique phenotype of remodelling relative to normoxic controls, including: (i) decreased citrate synthase and F1FO-ATPase activity but maintained protein content, (ii) markedly reduced aerobic capacity, and (iii) mild uncoupling of the mitochondrial proton gradient. These data suggest that turtle brain mitochondria respond to low oxygen stress with a unique suite of changes tailored towards neuroprotection.
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Chapter 18 Control of Oxidative Metabolism
Checkpoint 18.4 • How do the ATP mass acAon raAo and the IF1 protein
regulate ATP synthesis?
• What control mechanisms link glycolysis, the citric acid
cycle, and oxidaAve phosphorylaAon?
• Describe the advantages and disadvantages of oxygen
-based metabolism.
• How do cells minimize oxidaAve damage?
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