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The Oxidative Phosphorylation

The Oxidative Phosphorylation. Objectives. ATP as energy currency Mitochondria and the electron transport chain organization Inhibitors of the electron transport chain Oxidative phosphorylation and the uncoupling proteins The role of mitochondria in apoptosis. Adenosine Triphosphate (ATP).

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The Oxidative Phosphorylation

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  1. The Oxidative Phosphorylation

  2. Objectives • ATP as energy currency • Mitochondria and the electron transport chain organization • Inhibitors of the electron transport chain • Oxidative phosphorylation and the uncoupling proteins • The role of mitochondria in apoptosis

  3. Adenosine Triphosphate (ATP) Δ Gº -7.3 kcal/mol/bond

  4. Electron Transport Chain (ETC) • A system of electron transport that uses respiratory O2 to finally produce ATP (energy) • Located in the inner mitochondrial membrane • Final common pathway of metabolism • Electrons from food metabolism are transported to O2 • Uses maximum amount of body’s oxygen

  5. Metabolic breakdown ofenergy-yielding molecules Energy-rich reduced coenzymes Electrons (e-) lose their free energy Excess energy generates heat

  6. Matrix: Enz for oxidation of pyruvate Amino acids, fatty acids,TCA. Partial synthesis of urea, heme NAD,FAD, ADP ,Pi Mt RNA,DNA Inn M: Impermeable to H+, K+, Na+ ATP, ADP, pyruvate,

  7. Cytochromes • Each cytochrome is a protein that contains • Heme group (porphyrin ring + iron in Fe3+ state) • When cytochromes accept electron • Fe3+ is converted to Fe2+ • Fe2+ is reoxidized to Fe3+ when it donates electrons to the next carrier

  8. Complex III and IV • Complex III: Cytochrome bc1 • Complex IV: Cytochrome a + a3 Electrons flow from: • CoQ  Complex III  Cyt. c  Complex IV

  9. Electron Transport Chain

  10. Coupling of Oxidative Phosphorylation

  11. Complex I NADH dehydrogenase FMN Fe-S Centers Complex III Cytochrome b&c1 Heme-containing (porphyrin ring containing iron Coenzyme Q Cytochrome c ½O2 Cytochrome aa3 Cu ions Cytochrome oxidase Succinate dehydrogenase FAD H2O ComplexII Complex IV Components of the Electron Transport Chain & Organization of the chain

  12. Amytal CO Sodium Azide

  13. ?Uncouplers

  14. Uncoupling proteins (UCP) UCP1, also called thermogenin, is responsible for the activation of fatty acid oxidation and heat production in the brown adipocytes of mammals.

  15. cleavage of key proteins and resulting in the morphologic and biochemical changes characteristic of apoptotic cell death pores allow cytochrome c to leave and enter the cytosol +proapoptotic factors, activates a family of proteolytic enzymes ,the caspases

  16. Membrane Transport SystemsGlycerophosphate Dehydrogense Shuttle

  17. Malate dehydrogenase Shuttle

  18. Reference: • Lippincott 5th edition: :Bioenergetics

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