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Ch.19 Oxidative Phosphorylation - Coggle Diagram
Ch.19 Oxidative Phosphorylation
Function of electron-transport chain in mitochondria
structure of electron carriers
Cytochromes
• One-electron carriers
• Iron coordinating porphoryin ring derivatives
• a, b, or c differ by ring additions
Iron-Sulfur Clusters
• One-electron carriers
• Coordinating by cysteines in the protein
• Containing equal number of iron and sulfur atoms
Coenzyme Q or Ubiquinone
• Ubiquinone is a lipid-soluble conjugated dicarbonyl compound that readily accepts electrons.
• Upon accepting two electrons, it picks up two protons to give an alcohol, ubiquinol.
• Ubiquinol can freely diffuse in the membrane, carrying electrons with protons from one side of the membrane to another side.
• Coenzyme Q is a mobile electron carrier transporting electrons from Complexes I and Il to Complex Ill.
The Protein Compomemts of the Mitovhondrial Respiratory Chain
Complex 1 :red_flag: NADH:Ubiquinone Oxidoreductase
• One of the largest macro-molecular assemblies in the mammalian cell
• Over 40 different polypeptide chains, encoded by both nuclear and mitochondrial genes
• NADH binding site in the matrix side
• Noncovalently bound flavin mononucleotide (FMN) accepts two electrons from NADH.
• Several iron-sulfur centers pass one electron at a time toward the ubiquinone binding site.
NADH:Ubiquinone Oxidoreducase Is a Proton Pump
• Transfer of two electrons from NADH to ubiquinone is accompanied by a transfer of protons from the matrix (N) to the intermembrane space (P) .
• Experiments suggest that about four protons are transported per one NADH.
• Reduced coenzyme Q picks up two protons.
• Protons are transported by proton wires.
Complex 2 :red_flag: Succinate Dehydrogenase
• Electrons are passed, one at a time, via iron-sulfur centers to ubiquinone, which becomes reduced QH2
• Does not transport protons
• Succinate dehydrogenase is a single enzyme with dual roles:
convert succinate to fumarate in the citric acid cycle
capture and donate electrons in the electron transport chain
• FAD accepts two electrons from succinate
Comples 3 :red_flag: Ubiquinone:Cytochrome c Oxidoreductase
• Uses two electrons from QH2 to reduce two molecules of cytochrome c
• Additionally contains iron-sulfur clusters, cytochrome b, and cytochrome c
• Clearance of electrons from the reduced quinones via the Q-cycle results in translocation of four additional protons to the intermembrane space.
The Q cycle
• Experimentally, four protons are transported across the membrane per two electrons that reach cyt c.
• Two of the four protons come from QH2.
• The Q cycle provides a good model that explains how two additional protons are picked up from the matrix.
• Two molecules of QH2 become oxidized, releasing protons into the IMS.
• One molecule becomes rereduced, thus a net transfer of four protons per reduced coenzyme Q.
cycle
cycle 1
cycle 2
Overall Reaction
:star: Cytochrome c
The second mobile electron carrier
Ubiquinone moves through the membrane.
Cytochrome c moves through the intermembrane space.
A soluble heme-containing protein in the intermembrane space
Cytochrome c carries a single electron from the cytochrome bC1 complex to cytochrome oxidase.
Complex 4 :red_flag: Cytochrome Oxidase
• Mammalian cytochrome oxidase is a membrane protein with 13 subunits.
• Contains two heme groups: a and a3
• Contains copper ions
:star: Electron Flow Through Complex 4
Synthesis of ATP in mitochondria
Mitochondrial ATP Synthase Complex
Contains two functional units:
F1
soluble complex in the matrix
individually catalyzes the hydrolysis of ATP
F0
integral membrane complex
transports protons from IMS to matrix, dissipating the proton gradient
energy transferred to Fl to catalyze phosphorylation of ADP
Binding-Change Model
Translocation of three protons fuels synthesis of one ATP.
每3個H+進來,ATP生成
Complex Rotation
Net Production of ATP by Oxidation of Glucose (and Other Fuels) Varies
In prokaryotic systems, organelles do not segregate machinery, so all electron carriers can easily feed directly into the electron-transport chain.
In eukaryotic systems, organellar segregation prevents NADH from the cytosol from directly entering the electron-transport chain at Complex 1.
NAD* pools are kept segregated and cannot directly cross the mitochondrial inner membrane.
Two methods are used to feed the electrons from NADH from the cytosol into the mitochondria:
malate-aspartate shuttle
glycerol-3-phosphate shuttle
Building up the proton-motive force
Chemiosmotic Model for ATP Synthesis
Electron transport sets up a proton-motive force.
Energy of proton-motive force drives synthesis of ATP.
Inhibitors of the Electron Transport Chain Disrupt Oxidative Phosphorylation
氰化物中毒:使 cyt a3 失去接受電子能力
:star: Relationship of ETC and ATP Synthesis
As described, ATP synthesis requires electron transport.
But electron transport does not requires ATP synthesis.
Dinitrophenol (DNP) is an uncoupler解聯劑, allowing respiration to continue without ATP synthesis.
:star: Summary of the Electron Floe in the Respiratory Chain
Regulation of Oxidative Phosphorylation
Inhibitor of F1 (IF1)
prevents hydrolysis of ATP during low oxygen
only active at lower pH, encountered when electron transport it stalled (i.e., low oxygen)
Inhibition of OxPhos leads to accumulation of NADH.
causes feedback inhibition cascade up to PFK-I in glycoysis
Primarily regulated by substrate availability
NADH and ADP/Pi