The Citric Acid Cycle

1. The Citric Acid Cycle Joe Maleszewski March 25, 2003

2. Lecture Outline • What is metabolism? • Review of Glycolysis • Assault on Pyruvate • Overview of Kreb’s Cycle (TCA) • Reactions of Kreb’s Cycle • Regulation of Kreb’s Cycle • Where are we going next?

3. Metabolism • Metabolism is the sum of all chemical reactions within a cell (or whole organism), including energy-releasing breakdown of molecules and the synthesis of complex molecules • It is extraordinarily COMPLEX

5. Metabolism • The reactions of metabolism are MANY • In this class we will discuss some of the major reactions: • Glyco - Lysis (glycolysis) • The Citric Acid Cycle • The Electron Transport Chain • It is important to become familiar with some of the key players in these reactions • ATP • NAD/NADH • The various other intermediate compounds (many are sugars)

6. Adenosine Triphosphate (ATP) • Used primarily as the “chemical-storage” form of energy within the cell.

7. Nicotinamide Adenine Dinucleotide (NAD) Reduction Oxidation • Used primarily in the cell as an electron carrier to mediate numerous reactions

8. Nicotinamide Adenine Dinucleotide (NAD) Reduction Oxidation • Used primarily in the cell as an electron carrier to mediate numerous reactions

9. Review of Glycolysis • What’s the point of glycolysis? • Traps glucose within the cell • Produces energy in the form of NADH and ATP with minimal energy input • Produces products that are used in other metabolic pathways within the cell • Many more reasons

10. Review of Glycolysis What have we put in to this? What are we getting out of it? ATP X 2 ATP X 4 ADP X 4 NADH X 2 NAD X 2 ADP X 2

11. Review of Glycolysis

12. The Fate of Pyruvate • In the ABSENCE of oxygen - pyruvate gets fermented to oxidize NADH to NAD so that glycolysis (ATP production can continue.

13. The Fate of Pyruvate • In the PRESENCE of oxygen - Pyruvate gets turned into Acetyl CoA and then added to other molecules in order to liberate CO2 (the Calvin Cycle - backwards).

14. The Assault on Pyruvate • Pyruvate moves easily passed the porous outer mitochondrial membrane and is then transported through the inner membrane where it encouters…

15. The Pyruvate Dehydrogenase Multienzyme Complex

16. The Assault on Pyruvate • The Pyruvate Dehydrogenase multienzyme complex will “assimilate” Pyruvate into Acetyl CoA by “ripping off” Pyruvate’s CO2 “head” and attaching chemical parts to it’s “neck.”

17. The Assault on Pyruvate

18. The Assault on Pyruvate

19. Acetyl CoA moves on to the Kreb Cycle (The Citric Acid Cycle)

20. Regulation of Kreb’s Cycle • The regulation is mediated via allosteric inhibition by products on enzymes used previously in the cycle. • For example, an increase in Citrate will cause a decreased activity of Citrate Synthase • An increased NADH or Acetyl CoA will decrease Pyruvate Dehydrogenase activity

21. Where have we been?

22. Kreb’s Cycle Summary • Remember, we get 3-NADH from TCA along with the one we got from the Pyruvate DH reaction and then an FADH2 (a lot like NADH, but less reducing power) and an ATP and this is just from ONE Pyruvate molecule (remember: 2 Pyruvates per Glucose molecule)

23. Where are we going? • The NADH from Glycolysis & the NADH + FADH from the Citric Acid Cycle will now move on to the Electron Transport Chain.

24. Why?? • The ATP that we will yield from the oxidative phosphorylation of ATP (remember photosynthesis) will be MUCH greater than that of just glycolysis alone (like in Fermentation).

25. Respiration Summary