Electron Transport Chain and Oxidative Phosphorylation

Electron Transport Chain and Oxidative Phosphorylation

1. Happens at inner mitochondrial membrane

2. Chemiosmotic Theory

   • Utilizing proton gradient to synthesize ATP

3. 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

4. DG = -nFE

   • High E indicates a strong tendency to be reduced
     • Electrons are donated by the half reaction with the more negative E and accepted by the reaction with the more positive E

5. Electron Transport Chain

   • Four protein complexes in the inner mitochondrial membrane
   • Lipid soluble coenzyme (CoQ) and water soluble protein (cyt c) shuttle between protein complexes
   • Electrons fall in energy from Complexes I and II to Complex IV
   • Complexes
     • Each contains multiple redox centers consisting of Flavin mononucleotide (FMN) or Flavin Adenine Dinucleotide (FAD)
       • Initial electron acceptors for Complex I and II
       • Can carry two electrons by transferring at a time
     • Cytochromes a, b, or c
     • Iron-sulfur cluster
     • Complex I
       • NADH-CoQ Oxidoreductase
       • Electron transfer from NADH to Q
         • Electron Path: NADH --> FMN --> FeS --> Q --> FeS --> Q
       • 4 H+ transported out per 2 e-
     • Coenzyme Q (Ubiquinone)
       • Lipid soluble conjugated dicarbonyl
       • Accepts two electrons, picks up two protons to give an alcohol ubiquinol
       • Ubiquinol can freely diffuse in the membrane, carrying electrons with protons from one side to the other
     • Iron Sulfur Clusters
       • One electron carriers
       • Coordinated by cysteines in protein
       • Contain equal number of Fe and S atoms
     • Complex II
       • Aka: Succinate-CoQ Oxidoreductase, succinate dehydrogenase, flavoprotein 2
       • Three types of FeS clusters (4Fe-4S, 3Fe-4S, 2Fe-2S)
       • Electron Path: succinate --> FAD --> Fe3+ --> Q
     • Complex III
       • CoQ-Cytochrome c Oxidoreductase
       • CoQ passes electrons to cyt c and pumps H+ in a redox cycle known as the Q cycle
       • The main transmembrane protein in Complex III is the by cytochrome
       • Cytochromes are one-electron transfer units
     • Complex IV
       • Electrons crom cyt c are used in a four electron reduction of O2 to form H2O
       • Oxygen is the terminal electron acceptor in the electron transport chain

6. Oxidative Phosphorylation

   • Proton gradient is established across the cristae membrane in mitochondria
   • ATP Synthase
     • Made of two complexes, F1(matrix) and F0 (inner membrane), both of which have subunits
     • Alternating alpha and beta subunits in F1
       • Conformation of beta subunit changes between three different conformations, open, loose (ADP + Pi) and tight (ATP)
         • Takes a lot of energy to release ATP from tight binding
     • Gamma structure rotates
   • Inhibition
     • Rotenone inhibits Complex I, cyanide, azide, and CO inhibit complex IV, and oligomycin and DCCD inhibit ATP synthase
   • Uncouplers
     • Disrupt tight coupling between ETC and OP by dissipating proton gradient
     • Hydrophoobic molecules with a dissociable proton that shuttle across the membrane carrying protons
   • ATP-ADP Translocase
     • Moves ATP out of the of the mitochondria at the cost of 1 H+ each
   • Regulation
     • Lack of work means lack of demand for ATP
     • Oxidative phosphorylation is driven not by supply of fuel but by demand for energy
   • P/O Ratio
     • 2.5 for NADH electrons
     • 1.5 for FADH2 electrons

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