PowerPoint PresentationSlide 2Slide 3Peter Mitchell's Chemiosmotic TheoryOverview of Chemiosmotic TheoryEnergy Conversion Requires the Proton CircuitBasic Components of the Chemiosmotic TheoryBasic Components of the Chemiosmotic TheorySlide 9The Mitochondrion, the Powerhouse of the CellPeter Mitchell - Eccentric ScholarHow was Mitchell’s idea proven?The Nobel Prize in Chemistry 1978Pathway QuestionsSlide 15Slide 16The Electron Transport System Is A Series Of Coupled Redox ReactionsSlide 18Slide 19Slide 20Metabolic Fuel for Electron TransportHow is the energy released by redox reactions used to "pump" protons into the inter-membrane space?Slide 23Slide 24Complex I: NADH-ubiquinone oxidoreductaseComplex II: Succinate dehydrogenaseComplex III: Ubiquinone-cytochrome c oxidoreductaseThe Q CycleFour Steps of the Q CycleSlide 30Slide 31Cytochrome CComplex IV: Cytochrome c oxidaseATP Currency Exchange Ratios of NADH and FADH2Slide 35Electron Transport System:The Chemiosmotic Theory, redox reactions of the electron transport system, NAD/ATP exchange ratio Bioc 460 Spring 2008 - Lecture 29 (Miesfeld)Hydrogen cyanide is a deadly gas that blocks e- transport from complex IV to O2 in the ETSRotenone (rat poison) blocks e- transport through FeS clustersPassing the baton is analogous to passing along the e- in the ETS•The Electron Transport System converts redox energy into proton-motive force. In this “pathway” the oxidation of NADH and FADH2 is coupled to the reduction of O2 to form H2O. The proton motive force is used to induce conformational changes in the ATP synthase complex.•The Chemiosmotic Theory states that energy from redox reactions is translated into vectorial energy by coupling electron transfer to membrane bound proton pumps that transverse a proton impermeable membrane and thereby establish an electrochemical proton gradient. •The ATP currency exchange ratios of NADH and FADH2 reflect ATP synthesis in response to H+ movement through the ATP synthase complex. It takes 4 H+ to synthesize 1 ATP, and since NADH oxidation pumps across 10 H+, the exchange ratio is 2.5 ATP/NADH. However, FADH2 oxidation only results in 6 H+ being pumped across the membrane, and therefore the exchange ratio is 1.5 ATP/ FADH2.Key Concepts in the Electron Transport SystemThe Electron Transport System (ETS) is intimately linked to the process of oxidative phosphorylation, both of which take place within the mitochondrial matrix.Photosynthesis also uses a form of electron transport that is driven by light absorption rather than redox energy.Peter Mitchell's Chemiosmotic Theory•Oxidation of NADH and FADH2 in the mitochondrial matrix by the electron transport system links redox energy to ATP synthesis. •Chemiosmosis involves the outward pumping of H+ from the mitochondrial matrix through three protein complexes in the electron transport system (ETS complexes I, III, IV).•H+ flow back down the proton gradient through the membrane-bound ATP synthase complex in response to a chemical (H+ concentration) and electrical (separation of charge) differential.Overview of Chemiosmotic TheoryATP synthasecomplexElectron TransportSystemFADH2Ox PhosEnergy Conversion Requires the Proton CircuitBasic Components of the Chemiosmotic TheoryBasic Components of the Chemiosmotic Theory•Energy from redox reactions or light is translated into vectorial energy and a proton circuit.•Vectorial H+ pumping results in chemical gradient (pH) and a membrane potential ΔΨ (Δpsi)•Separation of charge is due to build-up of positively-charged protons (H+) and negative hydroxyl ions (OH-)Basic Components of the Chemiosmotic Theory•In mitochondria, the contribution of ΔΨ (ΔV) to ΔG is actually greater than that of ΔpH (the ΔpH across the mitochondrial membrane is only 1 pH unit)•In chloroplasts, the ΔpH contribution to ΔG is much more significant with ΔpH close to 3 pH units•Change in free energy (ΔG) for a membrane transport process is the sum of the ion concentration (RT·ln(C2/C1)) and the membrane potential (ZFΔV)•In mitochondria, the ZFΔV term makes a larger contribution than does RT·ln(C2/C1).The Mitochondrion, the Powerhouse of the CellA critical feature of the mitochondrion is the extensive surface area of the inner mitochondrial membrane which forms the proton-impermeable barrier required for chemiosmosis.Peter Mitchell - Eccentric ScholarHe established the Glynn Research Institute in the early 1960s with a research staff of less than twenty, and remained a private research institution for almost 30 years. Mitchell's uncle was Sir Godfrey Mitchell who owned George Wimpy and Company Limited, the largest construction company in England at the time.How was Mitchell’s idea proven?Using biochemical approaches:1. "inside-out" submitochondrial membrane vesicles that could be shown to pump protons into the interior of the vesicle when oxidizable substrate was made available.2. artificial vesicles containing bacterial rhodopsin protein were exposed to light•proton pumping by the bacteriorhodopsin protein resulted in both inward proton pumping•ATP synthesis on the vesicle surfaceThe Nobel Prize in Chemistry 1978 Peter Mitchell's speech at the Nobel Banquet, December 10, 1978:The philosopher Karl Popper, the economist F. A. Hayek, and the art historian K. H. Gombrich have shown that the creative process in science and art consists of two main activities: an imaginative jumping forward to a new abstraction or simplified representation, followed by a critical looking back to see how nature appears in the light of the new vision. The imaginative leap forward is a hazardous, unreasonable activity. Reason can be used only when looking critically back. Moreover, in the experimental sciences, the scientific fraternity must test a new theory to destruction, if possible. Meanwhile, the originator of a theory may have a very lonely time, especially if his colleagues find his views of nature unfamiliar, and difficult to appreciate.Pathway Questions1. What does the electron transport system/oxidative phosphorylation accomplish for the cell?–Generates ATP derived from oxidation of metabolic fuels accounting for 28 out of 32 ATP (88%) obtained from glucose catabolism.–Tissue-specific expression of uncoupling protein-1 (UCP1) in brown adipose tissue of mammals short-circuits the electron transport system and thereby produces heat for thermoregulation. 2. What is the overall net reaction of NADH
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