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Chapter 9

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Chapter 9

  1. 1. Lecture #4 Date _________ <ul><li>Chapter 9 – </li></ul><ul><li>Cellular Respiration: Harvesting Chemical Energy </li></ul>
  2. 2. Principles of Energy Harvest <ul><li>Catabolic pathway Fermentation Cellular Respiration </li></ul><ul><li>C 6 H 12 O 6 + 6O 2 ---> 6CO 2 + 6H 2 O + Energy (ATP + heat) </li></ul>
  3. 3. Redox reactions <ul><li>Oxidation-reduction </li></ul><ul><li>Adding e- reduces + charge) </li></ul><ul><li>Red uction is e- gain </li></ul><ul><li>Ox idation is e- loss </li></ul><ul><li>Reducing agent: e- donor </li></ul><ul><li>Oxidizing agent: e- acceptor </li></ul><ul><li>Energy is released because the e- lose potential energy when they end up closer to an electronegative atom. </li></ul>
  4. 4. Oxidizing agent in respiration <ul><li>NAD+ (nicotinamide adenine dinucleotide) </li></ul><ul><li>Removes electrons from food (series of reactions) </li></ul><ul><li>NAD + is reduced to NADH </li></ul><ul><li>Enzyme action: dehydrogenase </li></ul><ul><li>Oxygen is the eventual e- acceptor </li></ul>
  5. 5. Electron transport chains <ul><li>Electron carrier molecules (membrane proteins) </li></ul><ul><li>Shuttles electrons that release energy used to make ATP </li></ul><ul><li>Sequence of reactions that prevents energy release in 1 explosive step </li></ul><ul><li>Electron route: food---> NADH ---> electron transport chain ---> oxygen </li></ul>
  6. 6. Cellular respiration <ul><li>Respiration is a cumulative function of three metabolic stages: </li></ul><ul><li>Glycolysis: cytosol; degrades glucose into pyruvate (see pg 162-3) </li></ul><ul><li>Kreb’s Cycle: mitochondrial matrix; pyruvate into carbon dioxide (see pg 165) </li></ul><ul><li>Electron Transport Chain: inner membrane of mitochondrion; electrons passed to oxygen (see pg 166 ) </li></ul>
  7. 7. Glycolysis (Summary) <ul><li>1 Glucose ---> 2 pyruvate molecules </li></ul><ul><li>Energy investment phase : cell uses ATP to phosphorylate fuel </li></ul><ul><li>Energy payoff phase : ATP is produced by substrate-level phosphorylation and NAD+ is reduced to NADH by food oxidation </li></ul><ul><li>Net energy yield per glucose molecule : 2 ATP plus 2 NADH; no CO2 is released; occurs aerobically or anaerobically </li></ul>
  8. 8. Glycolysis in Detail <ul><li>Glycolysis generates ATP by substrate-level phosphorylation. </li></ul>Figure 9.7 Enzyme Enzyme ATP ADP Product Substrate P +
  9. 9. Glycolysis in Detail <ul><li>Energy Investment Phase </li></ul>1. Hexokinase transfers a phosphate from ATP to glucose 2. Phosphoglucosoisomerase rearranges glucose-6-phosphate to convert it to its isomer fructose-6-phosphate 3. Phosphofructokinase transfers a phosphate from ATP to glucose 4. Aldolase cleaves the sugar molecule into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate (isomers) 5. Isomerase converts dihydroxyacetone phosphate into glyceraldehyde-3-phosphate Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate H H H H H OH OH HO HO CH 2 OH H H H H O H OH HO OH P CH 2 O P H O H HO HO H HO CH 2 OH P O CH 2 O CH 2 O P HO H HO H OH O P CH 2 C O CH 2 OH H C CHOH CH 2 O O P ATP ADP Hexokinase Glucose Glucose-6-phosphate Fructose-6-phosphate ATP ADP Phosphoglucoisomerase Phosphofructokinase Fructose- 1, 6-bisphosphate Aldolase Isomerase Glycolysis 1 2 3 4 5 CH 2 OH Oxidative phosphorylation Citric acid cycle Figure 9.9 A
  10. 10. Glycolysis in Detail <ul><li>Energy Payoff Phase </li></ul>6. Triose phosphate dehydrogenase first oxidizes sugar by the transfer of e- and H+ to NAD+ and then it uses the energy released to attach a phosphate group to the oxidized substrate 7. Phosphoglykerokinase the phosphate added to the substrate is transferred to ADP resulting in two molecules of 3-phosphoglycerate 8. Phosphoglyceromutase relocates the remaining phosphate 9. Enolase causes a double bond to form in the substrate by extracting a water molecule to form phosphoenolpyruvate (PEP) 10. Pyruvate Kinase transfers a phosphate from PEP to ADP producing pyruvate 2 NAD + NADH 2 + 2 H + Triose phosphate dehydrogenase 2 P i 2 P C CHOH O P O CH 2 O 2 O – 1, 3-Bisphosphoglycerate 2 ADP 2 ATP Phosphoglycerokinase CH 2 O P 2 C CHOH 3-Phosphoglycerate Phosphoglyceromutase O – C C CH 2 OH H O P 2-Phosphoglycerate 2 H 2 O 2 O – Enolase C C O P O CH 2 Phosphoenolpyruvate 2 ADP 2 ATP Pyruvate kinase O – C C O O CH 3 2 6 8 7 9 10 Pyruvate O Figure 9.8 B
  11. 11. Glycolysis (Summary) <ul><li>1 Glucose ---> 2 pyruvate molecules </li></ul><ul><li>Energy investment phase : cell uses ATP to phosphorylate fuel </li></ul><ul><li>Energy payoff phase : ATP is produced by substrate-level phosphorylation and NAD+ is reduced to NADH by food oxidation </li></ul><ul><li>Net energy yield per glucose molecule : 2 ATP plus 2 NADH ; no CO2 is released; occurs aerobically or anaerobically </li></ul>
  12. 12. Glycolysis to the Citric Acid (Krebs) Cycle <ul><li>Before the citric acid cycle can begin Pyruvate must first be converted to acetyl CoA, which links the cycle to glycolysis </li></ul>CYTOSOL MITOCHONDRION NADH + H + NAD + 2 3 1 CO 2 Coenzyme A Pyruvate Acetyle CoA S CoA C CH 3 O Transport protein O – O O C C CH 3 Figure 9.10
  13. 13. <ul><li>Before the citric acid cycle can begin Pyruvate must first be converted to acetyl CoA, which links the cycle to glycolysis </li></ul>Glycolysis to the Citric Acid (Krebs) Cycle <ul><li>Pyruvate’s fully oxidized carboxyl group (-COO - ) is given off as a molecule of CO 2 </li></ul><ul><li>The remaining two carbon fragment is oxidized to form acetate (ionized form of acetic acid) and the enzymes are transferred to NAD + , storing the energy in the form of NADH </li></ul><ul><li>Coenzyme A is attached to the acetate by an unstable bond to form Acetyl CoA </li></ul>CYTOSOL MITOCHONDRION NADH + H + NAD + 2 3 1 CO 2 Coenzyme A Pyruvate Acetyle CoA S CoA C CH 3 O Transport protein O – O O C C CH 3 Figure 9.10
  14. 14. Kreb’s Cycle (Summary) <ul><li>If molecular oxygen is present……. </li></ul><ul><li>Each pyruvate is converted into acetyl CoA (begin w/ 2): CO2 is released; NAD+ ---> NADH; coenzyme A (from B vitamin), makes molecule very reactive </li></ul><ul><li>From this point, each turn 2 C atoms enter (pyruvate) and 2 exit (carbon dioxide) </li></ul><ul><li>Oxaloacetate is regenerated (the “cycle”) </li></ul><ul><li>For each pyruvate that enters: 3 NAD+ reduced to NADH; 1 FAD+ reduced to FADH2 (riboflavin, B vitamin); 1 ATP molecule </li></ul>
  15. 15. Krebs Cycle in Detail <ul><li>Acetyl CoA adds its two-carbon acetyl group to oxaloacetate, producing citrate </li></ul><ul><li>Citrate is converted to its isomer, isocitrate , by removal of one water and the addition of another </li></ul><ul><li>Isocitrate loses a CO2 molecule and the resulting compound is oxidized, reducing NAD+ to NADH, and forming alpha-ketogluterate </li></ul><ul><li>Another CO2 molecule is lost, and the resulting compound is oxidized, reducing NAD+ to NADH; the remaining molecule is then attached to coenzyme A by an unstable bond forming succinyl CoA </li></ul><ul><li>CoA is displaced by a phosphate group, which is transferred to GDP, forming GTP, and then to ADP, forming ATP (substrate-level phosphorylation) and succinate </li></ul><ul><li>Two hydrogens are transferred to FAD, forming FADH 2 and oxidizing succinate to fumarate </li></ul><ul><li>The addition of a water molecule rearranges bonds in the substrate forming malate </li></ul><ul><li>The substrate is oxidized, reducing NAD+ to NADH and regenerating oxaloacetate so it can be used in the cycle again </li></ul>Acetyl CoA NADH Oxaloacetate Citrate Malate Fumarate Succinate Succinyl CoA  -Ketoglutarate Isocitrate Citric acid cycle S CoA CoA SH NADH NADH FADH 2 FAD GTP GDP NAD + ADP P i NAD + CO 2 CO 2 CoA SH CoA SH CoA S H 2 O + H + + H + H 2 O C CH 3 O O C COO – CH 2 COO – COO – CH 2 HO C COO – CH 2 COO – COO – COO – CH 2 HC COO – HO CH COO – CH CH 2 COO – HO COO – CH HC COO – COO – CH 2 CH 2 COO – COO – CH 2 CH 2 C O COO – CH 2 CH 2 C O COO – 1 2 3 4 5 6 7 8 Glycolysis Oxidative phosphorylation NAD + + H + ATP Citric acid cycle Figure 9.12
  16. 16. Kreb’s Cycle (Summary) <ul><li>If molecular oxygen is present……. </li></ul><ul><li>Each pyruvate is converted into acetyl CoA (begin w/ 2): CO2 is released; NAD+ ---> NADH; coenzyme A (from B vitamin), makes molecule very reactive </li></ul><ul><li>From this point, each turn 2 C atoms enter (pyruvate) and 2 exit (carbon dioxide) </li></ul><ul><li>Oxaloacetate is regenerated (the “cycle”) </li></ul><ul><li>For each pyruvate that enters: 3 NAD+ reduced to NADH; 1 FAD+ reduced to FADH2 (riboflavin, B vitamin); 1 ATP molecule </li></ul>
  17. 17. Electron transport chain <ul><li>Cytochromes carry electron carrier molecules (NADH & FADH2) down to oxygen </li></ul><ul><li>Chemiosmosis : energy coupling mechanism </li></ul><ul><li>ATP synthase : produces ATP by using the H+ gradient (proton-motive force) pumped into the inner membrane space from the electron transport chain; this enzyme harnesses the flow of H+ back into the matrix to phosphorylate ADP to ATP (oxidative phosphorylation) </li></ul>
  18. 18. ATP Synthase INTERMEMBRANE SPACE H + H + H + H + H + H + H + H + P i + ADP ATP A rotor within the membrane spins clockwise when H + flows past it down the H + gradient. A stator anchored in the membrane holds the knob stationary. A rod (for “stalk”) extending into the knob also spins, activating catalytic sites in the knob. Three catalytic sites in the stationary knob join inorganic Phosphate to ADP to make ATP. MITOCHONDRIAL MATRIX Figure 9.14
  19. 19. Review: Cellular Respiration <ul><li>Glycolysis: 2 ATP (substrate-level phosphorylation) </li></ul><ul><li>Kreb’s Cycle: 2 ATP (substrate-level phosphorylation) </li></ul><ul><li>Electron transport & oxidative phosphorylation: 2 NADH (glycolysis) = 6ATP 2 NADH (acetyl CoA) = 6ATP 6 NADH (Kreb’s) = 18 ATP 2 FADH2 (Kreb’s) = 4 ATP </li></ul><ul><li>38 TOTAL ATP/glucose </li></ul>
  20. 20. Fermentation <ul><li>In the absence of oxygen, many cells use fermentation to produce ATP by substrate-level phosphorylation. In fermentation, pyruvate serves as an electron acceptor for oxidizing NADH back to NAD+, which can then be reused in glycolysis. The two common end products of fermentation are ethanol and lactate (ionized form of lactic acid). </li></ul>2 ADP + 2 P 1 2 ATP Glycolysis Glucose 2 NAD + 2 NADH 2 Pyruvate 2 Acetaldehyde 2 Ethanol (a) Alcohol fermentation 2 ADP + 2 P 1 2 ATP Glycolysis Glucose 2 NAD + 2 NADH 2 Lactate (b) Lactic acid fermentation H H OH CH 3 C O – O C C O CH 3 H C O CH 3 O – C O C O CH 3 O C O C OH H CH 3 CO 2 2 Figure 9.17
  21. 21. Related metabolic processes <ul><li>Fermentation: </li></ul><ul><ul><li>Alcohol - pyruvate to ethanol </li></ul></ul><ul><ul><li>Lactic acid - pyruvate to lactate </li></ul></ul><ul><li>Facultative anaerobes (yeast/bacteria) </li></ul><ul><li>Beta-oxidation: A metabolic sequence of lipid catabolism that breaks down fatty acids into two-carbon fragments that can enter the citric acid cycle as acetyl CoA </li></ul>
  22. 22. The catabolism of various foods <ul><li>Monomers of many organic molecules can be used as fuel for cellular respiration. </li></ul>Amino acids Sugars Glycerol Fatty acids Glycolysis Glucose Glyceraldehyde-3- P Pyruvate Acetyl CoA NH 3 Citric acid cycle Oxidative phosphorylation Fats Proteins Carbohydrates Figure 9.19
  23. 23. Control of Cellular Respiration <ul><li>Allosteric enzymes at certain points in the respiratory pathway respond to inhibitors and activators that help set the pace of glycolysis and the citric acid cycle. Phosphofructokinase, the enzyme that catalyzes step 3 of glycolysis is one such enzyme. It is stimulated by AMP (derived from ADP) but is inhibited by ATP and by citrate. This feedback regulation adjusts the rate of respiration as the cell’s catabolic and anabolic demands change. </li></ul>Glucose Glycolysis Fructose-6-phosphate Phosphofructokinase Fructose-1,6-bisphosphate Inhibits Inhibits Pyruvate ATP Acetyl CoA Citric acid cycle Citrate Oxidative phosphorylation Stimulates AMP + – – Figure 9.20

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