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BIOL 201 - Lectures 10 to 12

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Biology (Sci)
BIOL 201
Greg Brown

Lecture 10 Metabolism and real life ∗ Both carbohydrates and fats can serve to provide energy but… ∗ Carbohydrates (Glucose) is/are the body’s preferredsource of energy ∗ The only source of energy for the brain (blood‐brain barrier) and red blood cells (no mitochondria) ∗ High intensity exercise (sprinting) driven almost exclusively by anaerobic glycolysis ∗ Maximum sprint distance ~ 200m ∗ Pacing critical for longer distance races Starting fast on a race: Very bad, even if you slow down later ∗ Lactic acid build up early ∗ Slow down in pace allows for more aerobic metabolism in mid‐race H+ ∗ Last 100m: need for muscle ATP acute, lactic acid build up leads to increase in muscle ∗ High H inhibits PFK ∗ Glycolysis stops, muscles stop working The Wall ∗ Marathon: right pace, 75% calories from CHO, 25% from fats ∗ Maximum CHO energy storage: 2000 cals (good for 20miles) ∗ As race goes on, CHO becomes depleted. If CHO getsdepleted before race finishes you hit:The wall "It felt like an elephant had jumped out of a treeonto my shoulders and was making me carry it the rest of the way in” ‐Dan Beardsley ∗ CHO reserves depleted ∗ Fatty acids can’t supply energy in absence of CHO Why? OAA limiting for TCA cycle Brain, RBCs need glucose OAA used for gluconeogenesis in liver No way to provide muscles with adequate ATP to maintain pace The Atkins diet ∗ Very low CHO, average fat, protein ∗ When CHO reserves are low, body uses fat as sourceof energy. ∗ Protein provides source of OAA, glucose (through gluconeogenesis), but your breath smells bad Why? ∗ Low OAA in liver ∗ FA’s converted to acetyl CoA faster than acetyl CoA+ OAA can form citrate ∗ Acetyl CoAs combine to form acetoacetate, beta‐hydroxymalonate ∗ Released as ketones into blood ∗ Actetoacetate → acetone, can be detected in breath TCA cycle overview Reactions are coupled to the formation of a protongradient, which is an energy consuming process.. + NADH and FADH fo2med during cycle re‐oxidized to NAD and FAD through action of respiratory or electron transport chain Respiratory chain transfers electrons to 2 to form H 2. Coupled to formation of H + gradient across inner membrane Discharge of gradient coupled to ATP synthesis Lecture 11 Redox Reactions and the electron transfer chain ∗ Electrons are transferred from one carrier to the next in the electron transfer chain. ∗ Each electron transfer corresponds to a redox reaction ∗ One carrier loses an electron (oxidized) and passesit on to another carrier (reduced). ∗ Ex: succinate + FAD → fumarate + FADH 2 • Can be considered as two half‐reactions: Oxidation: Succinate → fumarate + 2 e + 2 H‐ + ‐ + Reduction: FAD + 2 e + 2 H → FADH 2 ‐ + 2 ‐ + Succinate + FAD +2e+ 2H →fumarate + FADH + 2e+ 2H +3 +2 + Next reaction in the chain: FADH + 2 2e (Non‐Heme Iron) → FAD + 2 Fe (NHI) + 2 H TCA cycle The electron transfer chain is also referred to therespiration train. Inhaled oxygen serves as the terminal electron acceptor for electrons being released in the Citric Acid cycle, water vapour is exhaled. Exhaled carbon dioxide comes from decarboxylations. Foodstuffs are oxidized, electrons are captured, transferred from intermediates to NAD and FAD to form NADH and FADH . 2 NAD is getting converted to NADH (Tri‐Carboxylic acid cycle output) 1. NADH gets re‐oxidized back to NAD, the first electron carrier is reduced, picking up the electron. 2. Electron Carrier A gives the Electron to carrier B. 3. Carrier B loses an electron, Electron carrier C gains an electron. 4. Carrier C transfers electrons to the terminal electron acceptor: Oxygen. 5. Water is formed from Oxygen. Redox Couples, redox potential & ∆G Each electron carrier has two forms (Redox Couple): Electron donor: Reduced form, Reducing agent. Electron acceptor: Oxidized form, oxidizing agent. + ‐ + NADH ↔ NAD + 2e + H + ‐ + FADH 2 ↔ FAD + 2e + 2H Eo’ The standard redox potential E ’ ranos reducing power of electron donor/acceptor pairs. A chemio‐ electrical term associated with a redox couple. Measured in volts, It ranks the reducing power of a redox couple. Thecouple is written as a reduction by convention. + ‐ + NAD + 2e + H → NADH E ’= ‐ 0.3oV ‐ + Pyruvate+ 2e + H → lactate E ’= ‐ 0o19V The more negative the E ’, toe greater the reducing power of the redox couple. The direction of electron transfer occurs from a more negative E ’ to aomore positive E ’. o NADH+ pyruvate+ H → NAD + lactate ∆G ’o ‐6.0 kcal/mol Energetically favorable, this is the direction in which the reaction will proceed spontaneously at equal concentrations. The greater the difference in E o’, the greater the free energy change released in the reaction. 1 ‐ + / 2 +22e + H → H O E ’2 + 0o82V (Lousy reducing agent, pretty unreactive, lower energy electrons) ∆G o’= ‐52.6.0 kcal/mol _____________________________________________________________________________________ I Complex I: Mediates electron transfer from NADH toCoQ or Ubiquinone III IV II Complex II: Mediates electron transfer from sucinate to CoQ to Ubiquinone Complex III: Mediates electron transfer from from CoQ to Cytocrome C Complex IV: Mediates electron transfer from Cytochrome C to Oxygen Energy of highly exergonic electron transport chainreaction captured as proton gradient permitting the synthesis of ATP from ADP and Phosphate. These electron transfer events are mediated by respiratory complexes, large multi‐subunit proteins that are integral components of the inner mitochondrialmembrane. Electrons flow from carriers with more negative redox potential to more positive redox potential. ∗ Results in a negative ΔG Large changes in standard potential of redox couples occur at proton pumping sites. Electrons are moving from a higher to a lower energy state. Big drops of redox potential occur across three complexes: I, III and IV. These are proton pumping complexes. Complex II is not associated with proton pumping, since the redox potential difference isn't that large. Respiratory Complexes are embedded in the inner mitochondrial membrane. ∗ Oxidation of NADH to NAD takes place on the matrix side of complex I. ∗ The electrons are transferred to an electron carrier embedded in the inner mitochondrial membrane, CoQ. ∗ From CoQ they pass to cytochrome C, another mobileelectron Carrier. ∗ From cytochrome C they pass to Oxygen to form water. This occurs on the matrix side of the inner membrane. The succinate to fumarate reaction occurs on the matrix side of the inner membrane. Transfer of electrons to CoQ, no associated proton pumping. These complexes are fairly immobile. Mobile carriers (CoQ/Cyt C) mediate the movement of electrons from one complex to the other. The mitochondria: We have two membranes, infoldings of inner membrane are called cristae. Respiratory complexes and ATP synthase are associated with
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