Biochemistry: A Short Course

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Electron Transport Chain/Respiratory Chain
Proton gradient formed Four large protein
complexes Mitochondria localized Energetically
favorable electron flow
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Mitochondrion Inner Membrane
Respiration site Surface area for humans ca. 3
football fields Highly impermeable (no
mitochondrial porins) Matrix and cytoplasmic
sides
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Mitochondria an Endosymbiotic Event
Semi- autonomous organelles All mitochondria
derived from one endosymbiotic event an
ancestor of louse-borne typhus (Rickettsia
prowazeki)
Why did mitochondria become ubiquitous in nature?
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Redox Potential a Measurement of Electron Flow
Electrons flow through the wire ions flow
through the salt bridge X- H X
½H2 Half-reaction defined as zero H e-
½H2 e.g. O2 negative NADH positive
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Standard Reduction Potentials
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Favorable Electron Flow NADH to O2
Net electron flow through electron transport
chain ½O2 2H 2e- H2O ?E?
0.82V NAD H 2e- NADH ?E? -
0.32V Subtracting reaction B from A ½O2
NADH H H2O NAD ?E?
1.14V ?G? -220 kJ mol-1
?G? -nF ? E? F 96,480 J mol-1 V-1
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Electron Transport Chain Components

• Protein complexes
• NADH-Q reductase
• Succinate dehydrogenase
• Cytochrome C reductase
• Cytochrome C oxidase

Bridging components Coenzyme Q and Cytochrome C
What is the driving force for this electron flow?
8
Coupled Electron-Proton Transfer Through NADH-Q
Oxidoreductase
FMN bridges NADH 2 e- donor with FeS 1 e-
acceptor L-shaped Complex I Overall
reaction NADH Q 5H NAD QH2 4H
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Coupled Electron-Proton Transfer Through NADH-Q
Oxidoreductase
H movement with 1 NADH
Iron-sulfur clusters (a.k.a. nonheme-iron
proteins) 2Fe 2S or 4Fe 4S complexes
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NADH-Q Oxidoreductase (Complex I) Structure
Largest of respiratory complexes Mammalian
system contains 45 polypeptide subunits 8 Fe-S
complexes 60 transmembrane helices
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Different Quinone (Q) Oxidation States
QH2 generated by complex I II Membrane-bound
bridging molecule Overall reaction QH2 2Cyt
Cox 2H Q 2Cyt Cred 4H
X
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• Oxaloacetate Enzyme Regeneration from Succinate
• Succinate Dehydrogenase
• Fumerase
• Malate Dehydrogenase

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Pathways that Contribute to the Ubiquinol Pool
Without Utilizing Complex I
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Alternative Q-Cycle Entry Points
Complex I Complex II (citric acid
cycle) Glycerol 3-phosphate shuttle Fatty acid
oxidation (electron-transferring-flavoprotein
dehydrogenase)
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Electron-Transport Chain Reactions in the
Mitochondria
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The Q Cycle
Electron transfer to Cytochrome c Reductase via 3
hemes and a Rieske iron-sulfur center Overall
reaction QH2 2Cyt Cox 2H Q 2Cyt
Cred 4H
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The Q Cycle
Electron transfer to Cytochrome c Reductase via 3
hemes and a Rieske iron-sulfur center Overall
reaction QH2 2Cyt Cox 2H Q
2Cyt Cred 4H
ISP iron sulfur protein
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The Q Cycle
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The Q Cycle
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Cytochrome c Oxidoreductase Structure
Intermembrane side

• Heme-containing homodimer with 11 subunit
  monomers
• Functions to
• Transfer e- to Cyt c
• Pump protons into the intermembrane space

Matrix side
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Cytochrome c Oxidase Proton Pumping and O2
Reduction
CuA/CuA
CuB
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Cytochrome c Oxidase O2 Reduction to H2O
Reaction shown 2Cyt Cred 2H ½ O2 2Cyt
Cox H2O Overall reaction 2Cyt Cred 4H
½ O2 2Cyt Cox H2O 2H
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Cytochrome c Oxidase
Intermembrane space
Oxygen requiring step 13 subunits 10 encoded by
nuclear DNA CuA/CuA prosthetic group
positioned near intermembrane space
O2 to H2O reduction site
Matrix
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Cytochrome c Oxidase
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Electron-Transport Chain Reactions in the
Mitochondria
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Electron-Transport Chain Reactions in the
Mitochondria
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Mitochondrial Electron-Transport Chain Components
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Superoxide Dismutase Deactivation Mechanism
Superoxide and Peroxide generation
Superoxide deactivation
Hydrogen peroxide
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Conditions Associated with Free-Radical Exposure
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Environmental Impact of Excessive Aquatic
Respiration
Dead Zone from Agricultural runoff Water sources
include Mississippi, Sabine, and Trinity Rivers
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Chapter 20 Problems 1-11