1. Citric Acid Cycle Generates Reductive Equivalents Utilized in Respiration

2. Citric Acid Cycle: A Two Stage Process
Stage One: C4 + C2 condensation C6 tricarboxylic acid
Oxidative decarboxylation 2 CO Succinyl CoA
Net Result: 2NADH + 2CO2 + Succinyl CoA

3. C4 + C2 Condensation Reaction
Condensation catalyzed by enzyme dimer Citrate Synthase
RxN
Driver

4. Citrate Synthase Reaction

5. Citrate Synthase Reaction

6. Citrate Synthase Reaction

7. Citrate Synthase Reaction

8. Citrate to Isocitrate Conversion via Aconitase
Hydroxyl shift for subsequent oxidative decarboxylation

9. Isocitrate Dehydrogenase: Oxidation and Decarboxylation
Oxalosuccinate not released from the enzyme

10. α-Ketoglutarate Dehydrogenase: Oxidation and Decarboxylation
How similar is α-ketoglutarate dehydrogenase with pyruvate dehydrogenase in terms of substrate components? Reaction mechanism?

11. Citric Acid Cycle Part Two: Oxaloacetate Regeneration
Succinyl Coenzyme A Synthetase couples hydrolysis of Coenzyme A (-33 kJ/mol) with GTP formation (-30 kJ/mol)
The energetics works but what about the reaction mechanism?

12. Succinyl CoA-Sythetase Generates GTP
What is the Nu:-, E, and leaving group with GTP generation?

13. Oxaloacetate Enzyme Regeneration from Succinate
Succinate Dehydrogenase
Fumerase
Malate Dehydrogenase

14. A Color-Coded Citric Acid Cycle
Isocitrate is prochiral
Succinate is a symmetric
molecule
Generated
products
include:
2CO2 + 3NADH + 1FADH2 + GTP + CoA

15. Citric Acid Energetics

16. Citric Acid Cycle Regulation Points
ATP and NADH are indicators of a high energy state
ADP an indicator of a low energy state
Regulatory sites include:
Isocitrate dehydrogenase
α-Ketoglutarate dehydrogenase
Pyruvate dehydrogenase

17. Citric Acid Cycle is a Source for Biosynthetic Precursors

18. Transamination Reaction

19. Citric Acid Cycle Intermediates: Replenished as Metabolites are Drawn
Off for Biosynthesis
Anapleurotic reactions lead to a replenishment of pathway
components (e.g. pyruvate carboxylase).

20. Problems: 1, 3, 5, 7 and 9