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Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
Krebs Cycle
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Krebs Cycle

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  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. 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. 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. 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. 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. Kreb’s Cycle www.freelivedoctor.com
  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. Citrate Synthase Reaction (First) <ul><li>Claisen condensation </li></ul><ul><li>-32.2kJ </li></ul>www.freelivedoctor.com
  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. 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. 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. 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. 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. Fumarase <ul><li>Addition of water to a double bond </li></ul><ul><li>-3.8kJ </li></ul>www.freelivedoctor.com
  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. 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. 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. 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. 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. 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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