Electron Transport Chain and Oxidative Phosphorylation

Happens at inner mitochondrial membrane
Chemiosmotic Theory
1. Utilizing proton gradient to synthesize ATP
Carbohydrates, lipids, and amino acids are reduced fuels for the cell, electrons from these are transferred to NAD+ or FAD to make NADH and FADH2, these can then be used in oxidative phosphorylation to make ATP
DG = -nFE
1. High E indicates a strong tendency to be reduced
  1. Electrons are donated by the half reaction with the more negative E and accepted by the reaction with the more positive E
Electron Transport Chain
1. Four protein complexes in the inner mitochondrial membrane
2. Lipid soluble coenzyme (CoQ) and water soluble protein (cyt c) shuttle between protein complexes
3. Electrons fall in energy from Complexes I and II to Complex IV
4. Complexes
  1. Each contains multiple redox centers consisting of Flavin mononucleotide (FMN) or Flavin Adenine Dinucleotide (FAD)
    1. Initial electron acceptors for Complex I and II
    2. Can carry two electrons by transferring at a time
  2. Cytochromes a, b, or c
  3. Iron-sulfur cluster
  4. Complex I
    1. NADH-CoQ Oxidoreductase
    2. Electron transfer from NADH to Q
      1. Electron Path: NADH --> FMN --> FeS --> Q --> FeS --> Q
    3. 4 H+ transported out per 2 e-
  5. Coenzyme Q (Ubiquinone)
    1. Lipid soluble conjugated dicarbonyl
    2. Accepts two electrons, picks up two protons to give an alcohol ubiquinol
    3. Ubiquinol can freely diffuse in the membrane, carrying electrons with protons from one side to the other
  6. Iron Sulfur Clusters
    1. One electron carriers
    2. Coordinated by cysteines in protein
    3. Contain equal number of Fe and S atoms
  7. Complex II
    1. Aka: Succinate-CoQ Oxidoreductase, succinate dehydrogenase, flavoprotein 2
    2. Three types of FeS clusters (4Fe-4S, 3Fe-4S, 2Fe-2S)
    3. Electron Path: succinate --> FAD --> Fe3+ --> Q
  8. Complex III
    1. CoQ-Cytochrome c Oxidoreductase
    2. CoQ passes electrons to cyt c and pumps H+ in a redox cycle known as the Q cycle
    3. The main transmembrane protein in Complex III is the by cytochrome
    4. Cytochromes are one-electron transfer units
  9. Complex IV
    1. Electrons crom cyt c are used in a four electron reduction of O2 to form H2O
    2. Oxygen is the terminal electron acceptor in the electron transport chain
Oxidative Phosphorylation
1. Proton gradient is established across the cristae membrane in mitochondria
2. ATP Synthase
  1. Made of two complexes, F1(matrix) and F0 (inner membrane), both of which have subunits
  2. Alternating alpha and beta subunits in F1
    1. Conformation of beta subunit changes between three different conformations, open, loose (ADP + Pi) and tight (ATP)
      1. Takes a lot of energy to release ATP from tight binding
  3. Gamma structure rotates
3. Inhibition
  1. Rotenone inhibits Complex I, cyanide, azide, and CO inhibit complex IV, and oligomycin and DCCD inhibit ATP synthase
4. Uncouplers
  1. Disrupt tight coupling between ETC and OP by dissipating proton gradient
  2. Hydrophoobic molecules with a dissociable proton that shuttle across the membrane carrying protons
5. ATP-ADP Translocase
  1. Moves ATP out of the of the mitochondria at the cost of 1 H+ each
6. Regulation
  1. Lack of work means lack of demand for ATP
  2. Oxidative phosphorylation is driven not by supply of fuel but by demand for energy
7. P/O Ratio
  1. 2.5 for NADH electrons
  2. 1.5 for FADH2 electrons

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Electron Transport Chain and Oxidative Phosphorylation

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	Erstellt von Sarah Emslie vor fast 9 Jahre