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OXIDATIVE PHOSPHORYLATION

OXIDATIVE PHOSPHORYLATION. 9/25/07. Provides Energy for:. _ Mechanical. _ Chemical. Work. _ Ionic. ATP _ Universal Carrier of Free Energy. Role of ATP in Metabolism. Know this structure It is the most important molecule in biochemistry. . The Concept. Energy rich molecules donate

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OXIDATIVE PHOSPHORYLATION

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  1. OXIDATIVE PHOSPHORYLATION 9/25/07

  2. Provides Energy for: _ Mechanical _ Chemical Work _ Ionic ATP _ Universal Carrier of Free Energy

  3. Role of ATP in Metabolism Know this structure It is the most important molecule in biochemistry.

  4. TheConcept Energy rich molecules donate electrons to specific coenzymes to form energy-rich reduced coenzymes These electrons are donated to the electron transport chain to form ATP 1 pair of electrons is donated per each reduced coenzyme H2 = H + H H = 1 electron+ 1 proton :H¯ = 2 electrons+ 1 proton (Hydride ion) + H+ = 1 proton

  5. Oxidized Reduced Electrochemical gradient

  6. Carriers and transport systems are used to move ions and molecules across this membrane • Membrane convoluted or folded = ↑ Surface Area ATP Synthetase complex 50% protein Glycolysis Cytoplasm (Cristae) ElectronTransport Contains the ATP Synthetase complex • Inner mitochondrial membrane • Is the final common pathway • by which electrons from food • molecules are used to make • ATP and molecular oxygen • acts as the final acceptor • of the electrons

  7. Citric acid cycle 2 e¯ 2 e¯ Citric acid cycle • Cytochromes ▬ Heme group ▬ Iron ▬ Ferric (Fe3+) ▬ Ferrous (Fe2+) Final acceptor of e-s is molecular oxygen NADH Dehydrogenase Cytochrome oxidase (Iron + copper) Complex V contains ATP Sythase • Series of Oxidation/Reduction reactions Electron transport chain ▬3 components • Flavoprotein ▬ NADH Dehydrogenase • CoQ (Quinone) ▬ Ubiquinone

  8. Cyanide Each one of these inhibitors will completely stop electron transport and thus all ATP production

  9. Three Main Tenets of the Mitchell Theory

  10. FAD+ Blocked by atractyoside (Plant toxin) FADH2 ATP ADP ATP Synthase This dissipates gradient Oligomycin blocks Lower pH More protons pH gradient Electrical gradient ATP Cytoplasm 1 NADH = 3 ATP 1 FADH2 = 2 ATP ChemiosmoticHypothesis of Electron Transport coupled to ADP Phosphorylation ▬“Mitchell Hypothesis” Features: • Protons transported from the matrix to the inner mitochondrial space results • in an electric gradient and a pH gradient • As the protons flow through the membrane channel back into the matrix • they drive ATP synthesis Occurs with energy utilized by ATP synthase This proton transport couples electron transport to oxidative phosphorylation

  11. O2 Electron Transport Electron transport coupled to phosphorylation of ADP  ATP ADP ADP ADP H2O ATP ATP ATP + Dinitrophenol (DNP) breaks down proton gradient Introduced in 1932 as weight reduction drug = Fatal hyperthermia High doses of aspirin ▬ results in fever O2 Electron transport continues Electron Transport No ADP phosphorylation Energy dissipated as heat H2O HEAT UncouplingofOxidativePhosphorylation

  12. Breaks down proton gradient Brown adipose tissue creates heat by thermogenesis Thermogenin = uncoupling protein ▬ UCP1 Mechanism is to ↑ FA oxidation which uncouples oxidation phosphorylation The energy is given off as heat

  13. Some mitochondrial myopathies caused by mutations in mtDNA InheritedDiseasesofOxidativePhosphorylation LIBER’S HEREDITARY OPTIC NEUROPATHY Bilateral loss of central vision occurs because of Neuroretinal degeneration Mutation in mitochondrial DNA Mitochondrial DNA is maternally inherited because allmitochondria come from the mother None come from the sperm because none from sperm enter the egg during fertilization 13 of the ~100 proteins in the mitochondrion are coded for by mtDNA Has mutation rate > 10x that of nuclear DNA

  14. Glycerophosphate shuttle 2ATP for each NADH transported into mitochondrion from the cytoplasm Malate-Aspartate shuttle 3ATP for each NADH

  15. 1 2 3 6 4 7 5 8 2 Shuttle systems to bring cytosolic NADH into mitochondria for oxidative phosphorylation 1) Glycerophosphate shuttle = 36 ATP 2) Malate-aspartate shuttle = 38 ATP Count ATPs: Anerobic glycolysis = 2 Glycolysis + CAC + oxidative phosphorylation = 38

  16. 2 Domains F1 F0 . . . 1 ATP = 3.3 H+ Revolves at 100 Hz (revolutions/s) This is sufficient to produce a turnover of The weight of our body of ATP each day! ATPsynthase: • Rotates in 120° stages • 100 Hz one complete revolution = 3 ATP • Need 10 H+

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