Transcript 6-Respiratory-chain

Overview of the respiratory chain
© Michael Palmer 2014
Functional stages in the respiratory chain
1. H2 is abstracted from NADH+H+ and from FADH2
2. The electrons obtained with the hydrogen are passed down a
cascade of carrier molecules located in complexes I–IV, then
transferred to O2
3. Powered by electron transport, complexes I, III, and IV expel
protons across the inner mitochondrial membrane
4. The expelled protons reenter the mitochondrion through ATP
synthase, driving ATP synthesis
Uncoupling proteins dissipate the proton gradient
© Michael Palmer 2014
The uncoupling action of dinitrophenol
© Michael Palmer 2014
The Racker experiment: bacteriorhodopsin can
drive ATP synthase
© Michael Palmer 2014
Molecules in the electron transport chain
© Michael Palmer 2014
Iron-containing redox cofactors
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Flavin-containing redox cofactors
© Michael Palmer 2014
The respiratory chain produces reactive oxygen
species as byproducts
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Redox reactions can be compartmentalized to
produce a measurable voltage
© Michael Palmer 2014
The redox potential (ΔE) is proportional to the free
energy (ΔG)
© Michael Palmer 2014
Redox potentials and free energies in the
respiratory chain
© Michael Palmer 2014
The first two redox steps in complex I
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The reduction of coenzyme Q involves protons and
electrons
© Michael Palmer 2014
The Q cycle (criminally simplified)
© Michael Palmer 2014
Reduction of oxygen by cytochrome C oxidase
(complex IV)
© Michael Palmer 2014
How is electron transport linked to proton
pumping?
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Some redox steps in the ETC are coupled to proton binding
and dissociation, which may occur at opposite sides of the
membrane. Example: Coenzyme Q cycle at complex III
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Redox steps that do not involve hydrogen directly need
a different mechanism in order to contribute to proton
pumping. Example: Sequence of iron-sulfur clusters and
hemes in complex IV
Linking electron movement to proton pumping: A
conceptual model
© Michael Palmer 2014
Proton pumping creates both a concentration
gradient and a membrane potential
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Structure of ATP synthase
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The binding-change model of ATP synthase
catalysis
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How does proton flux drive ATP synthase?
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Proton flux causes c chains to rotate within the F0
disk
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A hypothetical malate-oxaloacetate shuttle
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The malate-aspartate shuttle
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The glycerophosphate shuttle
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The two mitochondrial isocitrate dehydrogenases
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Nicotinamide nucleotide transhydrogenase couples
hydrogen transfer with proton transport
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At rest, transhydrogenase and the isocitrate
dehydrogenases form a futile cycle
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When ATP demand is high, transhydrogenase turns
into an auxiliary proton pump
© Michael Palmer 2014
Theoretical ATP per molecule of glucose
completely oxidized
© Michael Palmer 2014
Processes other than ATP synthesis that are
powered by the proton gradient
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Nicotinamide nucleotide transhydrogenase
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Uncoupling proteins; proton leak
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Secondary active transport:
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ATP4−/ADP3− antiport
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phosphate/H+ symport
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amino acid/H+ symport
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pyruvate/H+ symport