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Chapter 16

Chapter 16. The Citric Acid Cycle: CAC Kreb’s Cycle Tricarboxylic Acid Cycle: TCA. Key topics : To Know. The Citric Acid Cycle. Also called Tricarboxylic Acid Cycle (TCA) or Krebs Cycle. Three names for the same thing. Cellular respiration and intermediates for biosynthesis.

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Chapter 16

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  1. Chapter 16 The Citric Acid Cycle: CAC Kreb’s Cycle Tricarboxylic Acid Cycle: TCA

  2. Key topics: To Know The Citric Acid Cycle • Also called Tricarboxylic Acid Cycle (TCA) or Krebs Cycle. Three names for the same thing. • Cellular respiration and intermediates for biosynthesis. • Conversion of pyruvate to activated acetate • Reactions of the citric acid cycle • Anaplerotic reactions to regenerate the acceptor • Regulation of the citric acid cycle • Conversion of acetate to carbohydrate precursors in the glyoxylate cycle

  3. Discovered CAC in Pigeon Flight Muscle

  4. Cellular Respiration • Process in which cells consume O2 and produce CO2 • Provides more energy (ATP) from glucose than Glycolysis • Also captures energy stored in lipids and amino acids • Evolutionary origin: developed about 2.5 billion years ago • Used by animals, plants, and many microorganisms • Occurs in three major stages: • acetyl CoA production (This chapter) • acetyl CoA oxidation (This chapter) • electron transfer and oxidative phosphorylation (Chapter 19)

  5. Overall Picture

  6. Overall Picture Acetyl-CoA production occurs in the mitochondria. Acetyl-CoA enters the CAC. The area blocked off all takes place in the Mitochondrion. So, first pyruvate has to get transported from the cytoplasm into the mitochondrion. In this Figure, only Glycolysis is in the Cytoplasm.

  7. Pyr DH is a Complex Enzyme

  8. Pyruvate Dehydrogenase Model TEM

  9. Lipoic Acid is linked to a Lys (K)

  10. Remember HSCoA ? from Chapter 1 It is down here

  11. One Unit of Pyr DH EOC Problem 6: Tests your knowledge of PyrDH. EOC Problem 7: Thiamin deficiency and blood pyruvate.

  12. Pyr DH is a Cool Enzyme EOC Problem 5: NAD+ in oxidation and reduction reactions (a through f should be easy).

  13. Citrate Synthase Convention to write incoming Acetyl on Top EOC Problem 32, further on the thermodynamics of Citrate Synthase.

  14. Aconitase, the Ferris Wheel

  15. The Aconitase Iron Sulfur Complex

  16. Aconitase has More than One Role Mitochondrial aconitase: Citric Acid Cycle Cytosolic aconitase: 2 roles: 1. citrate  isocitrate 2. iron response regulator

  17. Aconitase binding iron/RNA To become an iron response regulator, aconitase changes it shape (due to lack of iron) so it can bind RNA.

  18. Isocitrate DH ΔGo’ = -21 kJ/mole Mn++ cofactor EOC Problem 8 is all about IsocitDH.

  19. αKG DH is Just Like Pyr DH TPP, lipoate FAD

  20. Succinyl CoA Synthetase : Substrate Level Phosphorylation One GTP = One ATP Nucleoside diphosphate kinase: GTP + ADP  GDP + ATP ΔGo’ = 0

  21. Succinate DH = Old Yellow

  22. Malonate was One of the First Competitive Inhibitors Known

  23. Fumarase: the addition of water in two parts

  24. Don’t Confuse Malate and Maleate

  25. Malate DH is Endothermic

  26. CAC Energetics

  27. Watch Where the Label Goes EOC Problem 18: Labeled glucose carbons and where they go in CAC.

  28. Citrate is Prochiral

  29. The Acetyl Portion does not get oxidized to CO2 Until the Second Round And it gets randomized at Succinate

  30. Energetics of Glycolysis and CAC in ATPs EOC Problems 1 and 2: Balanced equations for Glycolysis and CAC.

  31. CAC in Anaerobic Not-Respiratory Organisms It’s a 2 input FORK

  32. This is Why OAA  D, N, I, K, T, M

  33. Anaplerotic Reactions

  34. Regulation of CAC EOC Problem 30 and 31 on oxygen and NAD regulation of CAC.

  35. Pathway Proteins Form Functional Units but It’s Concentration Dependent

  36. Pathways are Protein Modules Flagella LPS Outer Membrane Peptidoglycan Cytoplasmic Membrane Glycolysis ATPase RNA

  37. In Animals CAC can not be used for Gluconeogensis from Ac-SCoA D, N, L, K, M, T, I Porphrins: heme (cytochromes, hemoglobin), chlorophyll E, Q, P, R

  38. InBacteria and Plants, Not Vertebrates Overall: 2 Ac-SCoA  Succinate Succinate  OAA NADH and FADH2 Oxaloacetate CAC

  39. Glyoxylate Cycle in Plants in a Membrane Body

  40. Linkage to Gluconeogenesis in Plants

  41. Regulation Linkage

  42. Things to Know and Do Before Class • Pyruvate DH…all three parts and cofactors. • Chemistry of each step in Citric Acid Cycle. • Overall CAC thermodynamics (which steps are at Eq and which are drivers. • Prochiral nature of citrate. • Amphibolic nature of CAC and why fermenters need almost all of CAC. • Importance of anaplerotic reactions and how they work. • Glyoxylate Cycle (mammals lack) but plants, some invertebrates and bacteria have it. What does it do? • EOC Problems 1-9, 16, 18, 19, 30-32.

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