Chapter 16 The Citric Acid Cycle: CAC Kreb’s Cycle Tricarboxylic Acid Cycle: TCA 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 Discovered CAC in Pigeon Flight Muscle 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) Overall Picture Overall Picture Acetyl-CoA production The area blocked off all occurs in the takes place in the mitochondria. Mitochondrion. So, first pyruvate has to get Acetyl-CoA enters the transported from the CAC. cytoplasm into the mitochondrion. In this Figure, only Glycolysis is in the Cytoplasm. Pyr DH is a Complex Enzyme Pyruvate Dehydrogenase Model TEM Lipoic Acid is linked to a Lys (K) Remember HSCoA ? from Chapter 1 It is down here One Unit of Pyr DH EOC Problem 6: Tests your knowledge of PyrDH. EOC Problem 7: Thiamin deficiency and blood pyruvate. Pyr DH is a Cool Enzyme EOC Problem 5: NAD+ in oxidation and reduction reactions (a through f should be easy). Citrate Synthase Convention to write incoming Acetyl on Top EOC Problem 32, further on the thermodynamics of Citrate Synthase. Aconitase, the Ferris Wheel The Aconitase Iron Sulfur Complex Aconitase has More than One Role Mitochondrial aconitase: Citric Acid Cycle Cytosolic aconitase: 2 roles: 1. citrate isocitrate 2. iron response regulator Aconitase binding iron/RNA To become an iron response regulator, aconitase changes it shape (due to lack of iron) so it can bind RNA. Isocitrate DH ΔGo’ = -21 kJ/mole Mn++ cofactor EOC Problem 8 is all about IsocitDH. αKG DH is Just Like Pyr DH TPP, lipoate FAD Succinyl CoA Synthetase : Substrate Level Phosphorylation One GTP = One ATP Nucleoside diphosphate kinase: GTP + ADP GDP + ATP ΔGo’ = 0 Succinate DH = Old Yellow Malonate was One of the First Competitive Inhibitors Known Fumarase: the addition of water in two parts Don’t Confuse Malate and Maleate Malate DH is Endothermic CAC Energetics Watch Where the Label Goes EOC Problem 18: Labeled glucose carbons and where they go in CAC. Citrate is Prochiral The Acetyl Portion does not get oxidized to CO2 Until the Second Round And it gets randomized at Succinate Energetics of Glycolysis and CAC in ATPs EOC Problems 1 and 2: Balanced equations for Glycolysis and CAC. CAC in Anaerobic Not-Respiratory Organisms It’s a 2 input FORK This is Why OAA D, N, I, K, T, M Anaplerotic Reactions Regulation of CAC EOC Problem 30 and 31 on oxygen and NAD regulation of CAC. Pathway Proteins Form Functional Units but It’s Concentration Dependent Pathways are Protein Modules Flagella LPS Outer Membrane Peptidoglycan ATPase Cytoplasmic Membrane Glycolysis RNA In Animals CAC can not be used for Gluconeogensis from Ac-SCoA D, N, L, K, M, T, I Porphrins: heme (cytochromes, E, Q, P, R hemoglobin), chlorophyll In Bacteria and Plants, Not Vertebrates Overall: 2 Ac-SCoA Succinate Succinate OAA NADH and FADH2 Oxaloacetate CAC Glyoxylate Cycle in Plants in a Membrane Body Linkage to Gluconeogenesis in Plants Regulation Linkage 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, 30-32. .