From Lehninger Principles of Biochemistry

1. Why is it so complicated? Keeping track of Carbons How is it regulated? From Lehninger Principles of Biochemistry

2. Why is it so complicated?

3. Citric acid cycle components are important biosynthetic intermediates Amphibolic pathway, i.e., serves in both catabolic & anabolic processes From Lehninger Principles of Biochemistry

4. Anaplerotic reactions replenish citric acid cycle intermediates Anaplerotic (meaning "filling up" in Greek) pathways replace lost carbon compounds that are drawn out of central metabolism to produce other cell constituents. TCA Cycle From Lehninger Principles of Biochemistry

5. 2. Keeping track of Carbons

6. Each turn of the citric acid cycle produces 3 NADH, 1 FADH2, 1 GTP (or ATP), and 2 CO2 TCA Cycle From Lehninger Principles of Biochemistry

7. Keeping track of the carbon atoms From oxaloacetate, not acetyl-CoA From Lehninger Principles of Biochemistry

9. From Lehninger Principles of Biochemistry

10. Under physiological conditions except for 1,3 & 4 all reaction have DG values closer to zero Standard free energy changes for TCA cycle DG' = -32.2 kJ/mol DG' = 29.7 kJ/mol DG' = 13.3 kJ/mol DG' = -3.8 kJ/mol DG' = -20.9 kJ/mol DG' = 0 kJ/mol DG' = -33.5 kJ/mol DG' = -2.9 kJ/mol From Lehninger Principles of Biochemistry

11. 3. How is it regulated? Under physiological conditions except for 1,3 & 4 all reaction have DG values closer to zero DG' = -32.2 kJ/mol Standard free energy changes for TCA cycle DG' = -20.9 kJ/mol DG' = -33.5 kJ/mol From Lehninger Principles of Biochemistry

12. Regulation of Citric Acid Cycle The citric acid cycle is regulated at its three exergonic steps From Lehninger Principles of Biochemistry

13. The Glyoxylate Cycle Electron micrograph of germinating cucumber seed In germinating seeds triacylglycerol is converted to acetyl-CoA & then to glucose using glyoxylate pathway

14. The Glyoxylate Cycle A variant of TCA for plants and bacteria • Acetate-based growth • Net synthesis of carbohydrates and other intermediates from acetate is not possible with TCA • Glyoxylate cycle offers a solution for plants and some bacteria and algae • The CO2-evolving steps are bypassed and an extra acetate is utilized • Isocitrate lyase and malate synthase are the short-circuiting enzymes

15. Glyoxalate Cycle (in plants, some invertebrates, and in some microoranisms, e.g., E. coli) From Lehninger Principles of Biochemistry

16. From Lehninger Principles of Biochemistry

17. From Lehninger Principles of Biochemistry

19. Chapter 19 Electron Transport & Oxidative Phosphorylation

20. From Lehninger Principles of Biochemistry

22. Ubiquinone (coenzyme Q) (from lipids lecture)

23. 6 carbon C6H12O6 + 6 O2  6 CO2 + 6 H2O 2 x 3 carbon 2 CO2 2 x 2 carbon The carbon is already converted to CO2. What is left is electrons in the form of NADH and FADH2. 2 x 2 CO2

24. From Garrett & Grisham

26. {80% proteins} {30-40% lipids & 60-70% proteins} Provide inner membrane with large surface area Intermembrane space • Outer Membrane • Contains porin • Allows free diffusion of molecules • with molecular weight less than • 10,000 Porins are transmembrane channels for small molecules • Inner Membrane • Impermeable to molecules & ions

28. Matrix • contains all of TCA cycle enzymes {except, succinate dehydrogenase which is located in the inner membrane} • contains circular DNA, ribosomes and enzymes required to synthesize proteins encoded within the mitochondrial genome From Lehninger Principles of Biochemistry

29. Separation of functional complexes of the respiratory chain Components of the electron transport chain can be purified from the mitochondrial inner membrane From Lehninger Principles of Biochemistry