What s the point? ATP! Electron Transport Chain ATP

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1 What s the point? Cellular Respiration The point Stage 4: is to make ATP! Electron Transport Chain ATP

2 Cellular respiration

3 ATP accounting so far Even we need a lot more ATP! Glycolysis 2 ATP Kreb s cycle 2 ATP Life takes a lot of energy to run, need to extract more energy than 4 ATP! There s got to be a better way! I need a lot more ATP! A working muscle recycles over 10 million ATPs per second

4 There is a better way! Electron Transport Chain series of proteins built into inner mitochondrial membrane along cristae transport proteins & enzymes transport of electrons down ETC linked to pumping of to create gradient yields ~36 ATP from 1 glucose! only in presence of O 2 (aerobic respiration) That sounds more like it! O 2

5 Mitochondria Double membrane outer membrane inner membrane highly folded cristae enzymes & transport proteins intermembrane space fluid-filled space between membranes Oooooh! Form fits function!

6 Electron Transport Chain Intermembrane space Inner mitochondrial membrane C Q NADH dehydrogenase Mitochondrial matrix cytochrome bc complex cytochrome c oxidase complex Q = ubiquinone c = cytochrome c

7 Remember the Electron Carriers? Glycolysis glucose G3P Krebs cycle 2 NADH 2x = 2 8 NADH 2 FADH 2 Time to break open the piggybank! x2 = 6

8 Electron Transport Chain NADH NAD + + H e p H e- + Building proton gradient! C intermembrane space inner mitochondrial membrane NADH e H Q FADH 2 NAD + NADH dehydrogenase H e FAD cytochrome bc complex e 2 + O H 2 O cytochrome c oxidase complex mitochondrial matrix What powers the proton ( ) pumps? e e

9 Stripping H from Electron Carriers Electron carriers pass electrons & to ETC H cleaved off NADH & FADH 2 electrons stripped from H atoms (protons) electrons passed from one electron carrier to next in mitochondrial membrane (ETC) flowing electrons = energy to do work transport proteins in membrane pump (protons) across inner membrane to intermembrane space TA-DA!! Moving electrons do the work! NADH Q e FADH 2 NAD + NADH dehydrogenase e FAD cytochrome bc complex C e 2 + O H 2 O cytochrome c oxidase complex NADH NAD + + H H e- + ADP + P i ATP H+ e p

10 But what pulls the electrons down the ETC? O 2 H 2 O electrons flow downhill to O 2 oxidative phosphorylation

11 Electron transport chain Consists of several protein complexes Aren t you glad you do not have to memorize this??

12 Electrons flow downhill Electrons move in steps from carrier to carrier downhill to oxygen each carrier more electronegative controlled oxidation controlled release of energy make ATP instead of fire!

13 Free energy (G) relative to O 2 (kcal/mol) Figure e NADH NAD FADH 2 40 FMN Fe S I 2 e Fe S FAD II Multiprotein complexes Q Cyt b III 30 Fe S Cyt c 1 Cyt c Cyt a IV 20 Cyt a e (originally from NADH or FADH 2 ) 0 2 H + 1 / 2 O 2 mo/bioflix/bf_cellularrespiration_demo.html H 2 O

14 We did it! Set up a gradient Allow the protons to flow through ATP synthase Synthesizes ATP proton-motive force ADP + P i ATP ADP + P i Are we there yet? ATP

15 Chemiosmosis: The Energy-Coupling Mechanism The diffusion of ions across a membrane build up of proton gradient just so could flow through ATP synthase enzyme to build ATP Electron transfer in the etc causes proteins to pump from the mitochondrial matrix to the intermembrane space then moves back across the membrane, passing through the ATP synthase ATP synthase uses the exergonic flow of to drive phosphorylation of ADP to ATP This is an example of chemiosmosis, the use of energy in a gradient to drive cellular work Chemiosmosis links the Electron Transport Chain to ATP synthesis So that s the point!

16 Peter Mitchell Proposed chemiosmotic hypothesis revolutionary idea at the time proton motive force

17 Pyruvate from cytoplasm Inner mitochondrial membrane Q Intermembrane space C Electron transport system Acetyl-CoA Krebs cycle NADH NADH CO 2 e - 1. Electrons are harvested and carried to the transport system. FADH 2 e - e - 3. Oxygen joins with protons to form water. 2. Electrons provide energy to pump protons across the membrane. H 2 O 1 O e - O 2 ATP Mitochondrial matrix 4. Protons diffuse back in down their concentration gradient, driving the synthesis of ATP. ATP ATP synthase

18 Cellular respiration 2 ATP 2 ATP ~36 ATP + +

19 Summary of cellular respiration C 6 H 12 O 6 + 6O 2 6CO 2 + 6H 2 O + ~40 ATP Where did the glucose come from? Where did the O 2 come from? Where did the CO 2 come from? Where did the CO 2 go? Where did the H 2 O come from? Where did the ATP come from? What else is produced that is not listed in this equation? Why do we breathe?

20 Taking it beyond C What is the final electron acceptor in Q e Electron Transport Chain? e FADH 2 O 2 NADH NAD + So what happens if O 2 unavailable? ETC backs up nothing to pull electrons down chain NADH & FADH 2 can t unload H ATP production ceases cells run out of energy and you die! NADH dehydrogenase FAD cytochrome bc complex e 2 + O H 2 O cytochrome c oxidase complex

21 Beyond glucose: Other carbohydrates Glycolysis accepts a wide range of carbohydrates fuels polysaccharides glucose ex. starch, glycogen hydrolysis other 6C sugars glucose modified ex. galactose, fructose

22 Beyond glucose: Proteins Proteins amino acids hydrolysis waste amino group = waste product excreted as ammonia, urea, or uric acid H H N H C R O C OH glycolysis Krebs cycle carbon skeleton = enters glycolysis or Krebs cycle at different stages

23 Beyond glucose: Fats Fats glycerol & fatty acids hydrolysis glycerol (3C) PGAL glycolysis fatty acids 2C acetyl groups acetyl coa Krebs cycle glycerol fatty acids enters glycolysis as AP PGAL Biology enter Krebs cycle as acetyl CoA

24 Carbohydrates vs. Fats Fat generates 2x ATP vs. carbohydrate more C in gram of fat more O in gram of carbohydrate so it s already partly oxidized fat carbohydrate

25 Metabolism Coordination of digestion & synthesis by regulating enzyme Digestion digestion of carbohydrates, fats & proteins all catabolized through same pathways enter at different points cell extracts energy from every source CO 2

26 Metabolism Coordination of digestion & synthesis by regulating enzyme Synthesis enough energy? build stuff! cell uses points in glycolysis & Krebs cycle as links to pathways for synthesis run the pathways backwards eat too much fuel, build fat pyruvate glucose Krebs cycle intermediaries amino acids Cells are versatile & thrifty acetyl CoA fatty acids

27 METABOLISM Chapter 8 An Introduction to Metabolism Metabolism = total of an organism s chemical reactions

28 Glycan Metabolism Nucleotide Metabolism Cofactors & Vitamins Lipid Metabolism Carbohydrate Metabolism Amino Acid Metabolism

29 Control of Respiration Feedback Control 2005-

30 Feedback Inhibition Regulation & coordination of production production is self-limiting final product is inhibitor of earlier step allosteric inhibitor of earlier enzyme no unnecessary accumulation of product A B C D E F G X enzyme 1 enzyme 2 enzyme 3 enzyme 4 enzyme 5 enzyme 6 allosteric inhibitor of enzyme 1

31 Respond to cell s needs Key points of control phosphofructokinase allosteric regulation of enzyme can t turn back step before splitting glucose AMP & ADP stimulate ATP inhibits citrate inhibits Why is this regulation important? Balancing act: availability of raw materials vs. energy demands vs. synthesis

32 Regulation Feedback mechanisms help regulate cellular respiration Ex. Feedback inhibition Phosphofructokinase (PFK) is the major enzyme in glycolysis that is controlled ATP, Citrate inhibits ADP, AMP stimulates

33 Versatility Glucose is not the only fuel that can be used in cellular respiration Other biomolecules can be converted into intermediates and used in cellular respiration

34 What s the point? The point is to make ATP! ATP

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