Chapter 16. The Citric Acid Cycle: CAC Kreb s Cycle Tricarboxylic Acid Cycle: TCA
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1 Chapter 16 The Citric Acid Cycle: CAC Kreb s Cycle Tricarboxylic Acid Cycle: TCA
2 The Citric Acid Cycle Key topics: To Know 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 O 2 and produce CO 2 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 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. Acetyl-CoA production occurs in the mitochondria. Acetyl-CoA enters the CAC.
7 Pyr DH is a Complex Enzyme
8 Pyruvate Dehydrogenase Model TEM
9 Lipoic Acid is linked to a Lys (K)
10 It is down here Remember HSCoA? from Chapter 1
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
14 Citrate Synthase Convention to write incoming Acetyl on Top EOC Problem 32, further on the thermodynamics of Citrate Synthase.
15 Aconitase, the Ferris Wheel
16 The Aconitase Iron Sulfur Complex
17 Aconitase has More than One Role Mitochondrial aconitase: Citric Acid Cycle Cytosolic aconitase: 2 roles: 1. citrate isocitrate 2. iron response regulator
18 Aconitase binding iron/rna To become an iron response regulator, aconitase changes it shape (due to lack of iron) so it can bind RNA.
19 Isocitrate DH ΔG o = -21 kj/mole Mn ++ cofactor EOC Problem 8 is all about IsocitDH.
20 αkg DH is Just Like Pyr DH TPP, lipoate FAD
21 Succinyl CoA Synthetase : Substrate Level Phosphorylation One GTP = One ATP Nucleoside diphosphate kinase: GTP + ADP GDP + ATP ΔG o = 0
22 Succinate DH = Old Yellow
23 Malonate was One of the First Competitive Inhibitors Known
24 Fumarase: the addition of water in two parts
25 Don t Confuse Malate and Maleate
26 Malate DH is Endothermic
27 CAC Energetics
28 Watch Where the Label Goes EOC Problem 18: Labeled glucose carbons and where they go in CAC.
29 Citrate is Prochiral
30 The Acetyl Portion does not get oxidized to CO 2 Until the Second Round And it gets randomized at Succinate
31 Energetics of Glycolysis and CAC in ATPs EOC Problems 1 and 2: Balanced equations for Glycolysis and CAC.
32 CAC in Anaerobic Not-Respiratory Organisms It s a 2 input FORK
33 OAA D, N, I, K, T, M This is Why
34 Anaplerotic Reactions
35 Regulation of CAC EOC Problem 30 and 31 on oxygen and NAD regulation of CAC.
36 Pathway Proteins Form Functional Units but It s Concentration Dependent
37 Pathways are Protein Modules Flagella LPS Outer Membrane Peptidoglycan Cytoplasmic Membrane Glycolysis ATPase RNA
38 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
39 In Bacteria and Plants, Not Vertebrates Overall: 2 Ac-SCoA Succinate Succinate OAA NADH and FADH 2 Oxaloacetate CAC
40 Glyoxylate Cycle in Plants in a Membrane Body
41 Linkage to Gluconeogenesis in Plants
42 Regulation Linkage
43 Things to Know and Do Before Class 1. Pyruvate DH all three parts and cofactors. 2. Chemistry of each step in Citric Acid Cycle. 3. Overall CAC thermodynamics (which steps are at Eq and which are drivers. 4. Prochiral nature of citrate. 5. Amphibolic nature of CAC and why fermenters need almost all of CAC. 6. Importance of anaplerotic reactions and how they work. 7. Glyoxylate Cycle (mammals lack) but plants, some invertebrates and bacteria have it. What does it do? 8. EOC Problems 1-9, 16, 18, 19,
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