Mitochondrial Electron Transfer

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Lecture 21

• Mitochondrial Electron Transfer

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Biological Electron Flow Does Work
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Mitochondrial Electron Carriers

• NADH and FADH2 (Flavoproteins)
• Dehydrogenases
• Iron-sulfur proteins
• Cytochromes
• Cu
• Ubiquinone (Coenzyme Q?CoQ)

Highly organized complexes on inner
mitochondrial membrane
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Nicotinamide-Adenine Dinucleotide
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Reduction of Flavin Nucleotides
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Iron-Sulfur Proteins (Fe-S)
Fe3 e ? Fe2
Fe-S clusters Fe between 3 and 2 oxidation
states
Redox range 2Fe-2S2/1-240 to -460
mV 4Fe-4S3/250 to 450mV
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Heme in cytochrome
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Electron-Transfer Complexes H Pumps
As electrons flow to O2, H flows out
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Electron transfer complexes

• I NADH Q oxidoreductase
• II Succinate dehydrogenase
• III Ubiquinone cytochrome c
• oxidoreductase
• IV Cytochrome oxidase

In between some complexeselectron carriers that
diffuse out of complex
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Carrier Order by Inhibition

• Carriers ahead of block are reduced
• Carriers behind block are oxidized

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Complex INADH Ubiquinone oxidoreductase
NADH H Q
NAD QH2
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Electron-Transfer Complexes H Pumps
As electrons flow to O2, H flows out
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Ubiquinone ? UQ ? CoQ
Two electron carrier
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Q cycleComplex III
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Complex IV
Redox centers Carry only 1e- at a time. Reactive
intermediates are generated.
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Order of Carriers Ascending Eo?
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Respiration in Mitochondria

• 3 reactions
• Substrate is oxidized
• O2 consumed (?H2O)
• ADP Pi ? ATP

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Uncoupling Agents and Conditions

• Allow electron flow without ATP synthesis
• Example 2,4-dinitrophenol (DNP)
• Others CCCP, ionophores, membrane disruption

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Efficiency of Oxidative Phosphorylation
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Observed P/O Ratios
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Phosphorylation
Substrate-level vs. Respiration-linked
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Chemiosmotic Energetics
In mitochondria ?GH15-25 kJ/mol H
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Predictions of Chemiosmotics
1. Electron transfer causes H flux 2.
Destruction of H gradient blocks ATP
synthesis 3. Artificially-induced H gradient
drives ATP synthesis without electron
transfer 4.Blocking ATP synthesis will eventually
inhibit electron transfer
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H Flux Across Mitochondrial Membrane
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Uncouplers Permeant H Carriers
Destroys H gradient