Kreb’s Cycle  (aka, tricarboxylic acid (TCA)cycle, citric acid cycle) “ The wheel is turnin’ and the sugar’s a burnin’” ww...
Overall goal  <ul><li>Makes ATP </li></ul><ul><li>Makes NADH  </li></ul><ul><li>Makes FADH 2 </li></ul><ul><li>Requires so...
Geography <ul><li>Glycolysis in the cytosol </li></ul><ul><li>Krebs in mitochondrial matrix </li></ul><ul><li>Mitochondrio...
Conversion of pyruvate to Acetyl CoA <ul><li>2 per glucose (all of Kreb’s) </li></ul><ul><li>Oxidative decarboxylation </l...
Fates of Acetyl CoA <ul><li>In the presence of CHO an using energy </li></ul><ul><ul><li>Metabolized to CO 2 , NADH, FADH ...
Kreb’s Cycle www.freelivedoctor.com
Net From Kreb’s <ul><li>Oxidative process </li></ul><ul><ul><li>3 NADH </li></ul></ul><ul><ul><li>FADH 2 </li></ul></ul><u...
Citrate Synthase Reaction (First) <ul><li>Claisen condensation </li></ul><ul><li>-32.2kJ </li></ul>www.freelivedoctor.com
Aconitase Reaction <ul><li>Forms isocitrate </li></ul><ul><li>Goes through alkene intermediate (cis-aconitate) </li></ul><...
Isocitrate Dehydrogenase <ul><li>All dehydrogenase reactions make NADH or FADH 2   </li></ul><ul><li>Oxidative decarboxyla...
α -ketoglutarate dehydrogenase <ul><li>Same as pyruvate dehydrogenase reaction </li></ul><ul><li>Formation of thioester  <...
Succinyl CoA synthetase <ul><li>Hydrolysis of thioester  </li></ul><ul><ul><li>Releases CoASH </li></ul></ul><ul><ul><li>E...
Succinate dehydrogenase <ul><li>Dehydrogenation </li></ul><ul><li>Uses FAD </li></ul><ul><ul><li>NAD used to oxidize oxyge...
Fumarase <ul><li>Addition of water to a double bond </li></ul><ul><li>-3.8kJ </li></ul>www.freelivedoctor.com
Malate Dehydrogenase <ul><li>Oxidation of secondary alcohol to ketone </li></ul><ul><li>Makes NADH </li></ul><ul><li>Regen...
Net From Kreb’s <ul><li>Oxidative process </li></ul><ul><ul><li>3 NADH </li></ul></ul><ul><ul><li>FADH 2 </li></ul></ul><u...
Total Energy per glucose <ul><li>Cytosol </li></ul><ul><ul><li>Glycolysis </li></ul></ul><ul><ul><ul><li>2 NADH </li></ul>...
Total Energy/glucose <ul><li>In mitochondrion: </li></ul><ul><ul><li>Each NADH makes 2.5 ATP </li></ul></ul><ul><ul><li>Ea...
Total Energy/ glucose <ul><li>Cytosol </li></ul><ul><ul><li>2 ATP </li></ul></ul><ul><ul><li>2 NADH </li></ul></ul><ul><ul...
ATP/glucose <ul><li>Eukaryotes </li></ul><ul><ul><li>Mitochondrial:  25 ATP </li></ul></ul><ul><ul><li>Cytosolic:   5 or 7...
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Membrane Dynamics1

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Membrane Dynamics1

  1. 1. Kreb’s Cycle (aka, tricarboxylic acid (TCA)cycle, citric acid cycle) “ The wheel is turnin’ and the sugar’s a burnin’” www.freelivedoctor.com
  2. 2. Overall goal <ul><li>Makes ATP </li></ul><ul><li>Makes NADH </li></ul><ul><li>Makes FADH 2 </li></ul><ul><li>Requires some carbohydrate to run </li></ul>www.freelivedoctor.com
  3. 3. Geography <ul><li>Glycolysis in the cytosol </li></ul><ul><li>Krebs in mitochondrial matrix </li></ul><ul><li>Mitochondrion </li></ul><ul><ul><li>Outer membrane very permeable </li></ul></ul><ul><ul><ul><li>Space between membranes called intermembrane space (clever huh!) </li></ul></ul></ul><ul><ul><li>Inner membrane (cristae) </li></ul></ul><ul><ul><ul><li>Permeable to pyruvate, </li></ul></ul></ul><ul><ul><ul><li>Impermeable to fatty acids, NAD, etc </li></ul></ul></ul><ul><ul><li>Matrix is inside inner membrane </li></ul></ul>www.freelivedoctor.com
  4. 4. Conversion of pyruvate to Acetyl CoA <ul><li>2 per glucose (all of Kreb’s) </li></ul><ul><li>Oxidative decarboxylation </li></ul><ul><li>Makes NADH </li></ul><ul><li>-33.4kJ </li></ul>www.freelivedoctor.com
  5. 5. Fates of Acetyl CoA <ul><li>In the presence of CHO an using energy </li></ul><ul><ul><li>Metabolized to CO 2 , NADH, FADH 2 ,GTP and, ultimately, ATP </li></ul></ul><ul><li>If energy not being used (Lots of ATP present) </li></ul><ul><ul><li>Made into fat </li></ul></ul><ul><li>If energy being used, but no CHO present </li></ul><ul><ul><li>Starvation </li></ul></ul><ul><ul><li>Forms ketone bodies (see fat metabolism slides) </li></ul></ul><ul><ul><li>Danger! </li></ul></ul>www.freelivedoctor.com
  6. 6. Kreb’s Cycle www.freelivedoctor.com
  7. 7. Net From Kreb’s <ul><li>Oxidative process </li></ul><ul><ul><li>3 NADH </li></ul></ul><ul><ul><li>FADH 2 </li></ul></ul><ul><ul><li>GTP </li></ul></ul><ul><li>X 2 per glucose </li></ul><ul><ul><li>6 NADH </li></ul></ul><ul><ul><li>2 FADH 2 </li></ul></ul><ul><ul><li>2 GTP </li></ul></ul><ul><li>All ultimately turned into ATP (oxidative phosphorylation…later) </li></ul>www.freelivedoctor.com
  8. 8. Citrate Synthase Reaction (First) <ul><li>Claisen condensation </li></ul><ul><li>-32.2kJ </li></ul>www.freelivedoctor.com
  9. 9. Aconitase Reaction <ul><li>Forms isocitrate </li></ul><ul><li>Goes through alkene intermediate (cis-aconitate) </li></ul><ul><ul><li>elimination then addition </li></ul></ul><ul><li>13.3kJ </li></ul>www.freelivedoctor.com
  10. 10. Isocitrate Dehydrogenase <ul><li>All dehydrogenase reactions make NADH or FADH 2 </li></ul><ul><li>Oxidative decarboxylation </li></ul><ul><li>-20.9kJ </li></ul><ul><li>Energy from increased entropy in gas formation </li></ul>www.freelivedoctor.com
  11. 11. α -ketoglutarate dehydrogenase <ul><li>Same as pyruvate dehydrogenase reaction </li></ul><ul><li>Formation of thioester </li></ul><ul><ul><li>endergonic </li></ul></ul><ul><ul><li>driven by loss of CO 2 </li></ul></ul><ul><ul><ul><li>increases entropy </li></ul></ul></ul><ul><ul><ul><li>exergonic </li></ul></ul></ul><ul><li>-33.5kJ </li></ul>www.freelivedoctor.com
  12. 12. Succinyl CoA synthetase <ul><li>Hydrolysis of thioester </li></ul><ul><ul><li>Releases CoASH </li></ul></ul><ul><ul><li>Exergonic </li></ul></ul><ul><li>Coupled to synthesis of GTP </li></ul><ul><ul><li>Endergonic </li></ul></ul><ul><ul><li>GTP very similar to ATP and interconverted later </li></ul></ul><ul><li>-2.9kJ </li></ul>www.freelivedoctor.com
  13. 13. Succinate dehydrogenase <ul><li>Dehydrogenation </li></ul><ul><li>Uses FAD </li></ul><ul><ul><li>NAD used to oxidize oxygen-containing groups </li></ul></ul><ul><ul><ul><li>Aldehydes </li></ul></ul></ul><ul><ul><ul><li>alcohols </li></ul></ul></ul><ul><ul><li>FAD used to oxidize C-C bonds </li></ul></ul><ul><ul><li>0kJ </li></ul></ul>www.freelivedoctor.com
  14. 14. Fumarase <ul><li>Addition of water to a double bond </li></ul><ul><li>-3.8kJ </li></ul>www.freelivedoctor.com
  15. 15. Malate Dehydrogenase <ul><li>Oxidation of secondary alcohol to ketone </li></ul><ul><li>Makes NADH </li></ul><ul><li>Regenerates oxaloacetate for another round </li></ul><ul><li>29.7 kJ </li></ul>www.freelivedoctor.com
  16. 16. Net From Kreb’s <ul><li>Oxidative process </li></ul><ul><ul><li>3 NADH </li></ul></ul><ul><ul><li>FADH 2 </li></ul></ul><ul><ul><li>GTP </li></ul></ul><ul><li>X 2 per glucose </li></ul><ul><ul><li>6 NADH </li></ul></ul><ul><ul><li>2 FADH 2 </li></ul></ul><ul><ul><li>2 GTP </li></ul></ul><ul><li>All ultimately turned into ATP (oxidative phosphorylation…later) </li></ul>www.freelivedoctor.com
  17. 17. Total Energy per glucose <ul><li>Cytosol </li></ul><ul><ul><li>Glycolysis </li></ul></ul><ul><ul><ul><li>2 NADH </li></ul></ul></ul><ul><ul><ul><li>2 ATP </li></ul></ul></ul><ul><li>Mitochondrion </li></ul><ul><ul><li>Pyruvate dehydrogenase </li></ul></ul><ul><ul><ul><li>2 NADH </li></ul></ul></ul><ul><li>Krebs </li></ul><ul><ul><li>6 NADH </li></ul></ul><ul><ul><li>2 FADH 2 </li></ul></ul><ul><ul><li>2 GTP </li></ul></ul>www.freelivedoctor.com
  18. 18. Total Energy/glucose <ul><li>In mitochondrion: </li></ul><ul><ul><li>Each NADH makes 2.5 ATP </li></ul></ul><ul><ul><li>Each FADH 2 makes 1.5 ATP </li></ul></ul><ul><ul><li>GTP makes ATP </li></ul></ul><ul><li>So… </li></ul><ul><ul><li>From in mitochondrion </li></ul></ul><ul><ul><ul><li>8 NADH X 2.5 ATP/NADH = 20 ATP </li></ul></ul></ul><ul><ul><ul><li>2 FADH 2 X 1.5 ATP/FADH 2 = 3 ATP </li></ul></ul></ul><ul><ul><ul><li>2 GTP X 1 ATP / GTP = 2 ATP </li></ul></ul></ul><ul><ul><ul><li>TOTAL in mitochondrion 25 ATP </li></ul></ul></ul>www.freelivedoctor.com
  19. 19. Total Energy/ glucose <ul><li>Cytosol </li></ul><ul><ul><li>2 ATP </li></ul></ul><ul><ul><li>2 NADH </li></ul></ul><ul><ul><ul><li>NADH can’t get into mitochondrion </li></ul></ul></ul><ul><ul><ul><li>In eukaryotes two pathways, </li></ul></ul></ul><ul><ul><ul><ul><li>transferred to FADH 2 </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>get 1.5 ATP/ FADH 2 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Or transferred to NADH </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Get 2.5 ATP/ NADH </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>(Not a problem in prokaryotes (why?)) </li></ul></ul></ul></ul><ul><ul><li>2 NADH X 1.5 ATP = 3 ATP </li></ul></ul><ul><ul><li>Or 2 NADH X 2.5 ATP = 5 ATP </li></ul></ul><ul><ul><ul><ul><ul><li>+ =2 ATP </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Total 3+ 2 or 5 + 2 so either 5 or 7 </li></ul></ul></ul></ul></ul>www.freelivedoctor.com
  20. 20. ATP/glucose <ul><li>Eukaryotes </li></ul><ul><ul><li>Mitochondrial: 25 ATP </li></ul></ul><ul><ul><li>Cytosolic: 5 or 7 ATP </li></ul></ul><ul><ul><li>Total 30 or 32 ATP/glucose </li></ul></ul><ul><ul><li>30 ATP X 7.3kcal X 4.18 kJ = 915 kJ </li></ul></ul><ul><ul><ul><ul><ul><li>ATP kcal </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>If 32 ATP = 976 kJ </li></ul></ul></ul></ul></ul><ul><li>Prokaryotes </li></ul><ul><ul><li>32 ATP X 7.3kcal X 4.18 kJ = 976 kJ </li></ul></ul><ul><ul><ul><ul><ul><li>ATP kcal </li></ul></ul></ul></ul></ul>www.freelivedoctor.com

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