1. Pyruvate Oxidation and Krebs Cycle
Jennifer
Agnes
Hilary
Lucy

2. Quick Review
-In glycolysis, the first stage of cellular respiration, glucose, a 6-C chain molecule was broken down into 2 pyruvate molecules in a series of 10 steps. Net payoff: 2 ATP (2 used, 4 produced) 2 NADH -The pyruvate then moves from the cytoplasm into the mitochondrial matrix.

3. Glycolysis

4. REMEMBER: After Glycolysis which takes place in the cytosol, all the steps take place in the mitochondria

5. Depending on the presence of oxygen, the pyruvate will either enter a fermentation process (lactic acid or alcohol) or proceed towards the Krebs Cycle.

6. -> 2 acetyl-CoA + 2 NADH + 2H2+ 2 CO2
Pyruvate Oxidation
overall purpose: convert Pyruvate into Acetyl-CoA
2 pyruvate + 2 NAD + 2 CoA 
-> 2 acetyl-CoA + 2 NADH + 2H2+ 2 CO2
acetyl CoA - central molecule in energy metabolism
proteins, lipids, can also be broken down into acetyl CoA
can produce fat or ATP, depending on ATP levels in the cell

7. -> 2 acetyl-CoA + 2 NADH + 2H2+ 2 CO2
Pyruvate Oxidation
net production:
2 NADH - electron transport chain
2 acetyl-CoA - enter Krebs Cycle
2H+ - dissolves in matrix
2 CO2 - diffuses out of cell
2 pyruvate + 2 NAD + 2 CoA 
-> 2 acetyl-CoA + 2 NADH + 2H2+ 2 CO2

8. - transition step between glycolysis and Kreb's Cycle
Pyruvate Oxidation
- transition step between glycolysis and Kreb's Cycle

9. 1. carboxyl functional group removed as CO2 - decarboxylation catalyzed by enzyme pyruvate decarboxylase
2. redox reaction that converts NAD+ -> NADH and H+
pyruvate is oxidized, NAD+ is reduced
3. CoA is attached to acetate compound to form Acetyl CoA -> unstable carbon-sulfur bond in preparation for the Krebs Cycle

10. Krebs Cycle metabolic pathway amphibolic (catabolism and anabolism)
cyclic -> oxacetate reused 
produces precursors to ATP
net production: 
3 NADH x 2 = 6 NADH
1 FADH2 x 2 = 2 FADH2
- later converted to ATP in the electron transport chain

11. Krebs Cycle Equation
Oxaloacetate + Acetyl-CoA+ ADP + Pi +3NAD+ + FAD   -->    CoA+ATP+3NADH +3H++FADH2+ 2CO2+ Oxaloacetate

12. Krebs Cycle: The Simple Version

14. Also known as the citric or tricarboxylic acid cycle (TCA) because citric acid has THREE CARBOXYL groups

15. Hans Krebs ( )
German-born British biochemist who received a Nobel Prize in Physiology for the discovery of the Krebs Cycle. 
     -Krebs discovered that citrate formed when pyruvate and oxaloacetate
      combined, thus explaining the reason why the reactions form a cycle.
Krebs also discovered the urea cycle with another biochemist, Kurt Henseleit. In this cycle, ammonia is converted to urea in the tissues of mammals; being far less toxic than ammonia, urea is excreted in the urine of most mammals.

16. Step1: Acetyl+Oxaloacetate= Citrate CoA-SH freed
Interactive Krebs Cycle (with enzyme names)
Step1: Acetyl+Oxaloacetate= Citrate
CoA-SH freed
Enzyme:  Citrate Synthase
Step 2: Citrate rearranged to isocitrate
Enzyme:Aconitase
Step 3: Oxidative decarboxylation: Loss of 2 H atoms to NAD+ (forms NADH + H+), removal of C as CO2,  isocitrate becomes a-ketoglutarate
Enzyme:  Isocitrate DH
Step 4: Succinyl-CoA produced. Oxidative decarboxylation occurs again
Enzyme:a-ketoglutarate DH (multi-enzyme complex)

17. Step 5: ATP formed via substrate level phosphorylation, Succinyl- CoA becomes succinate
Enzyme:  Succinate thiokinase (Succinyl-CoA Synthetase)
+ Nucleoside diphosphate kinase
Step 6: Succinate oxidized to fumarate (FADH2 produced)
Enzyme:  Succinate DH
Step 7: Fumarate hydrated to produce malate.
Enzyme:  Fumarase
Step 8: Malate is oxidized into oxaloacetate.
Enzyme:  Malate DH

18. C atoms in glucose - what happens to them?
Glucose - has a 6-carbon backbone 
by the end of Krebs Cycle, all of them have been oxidized into CO2
- released from cell as waste

19. Summary of Krebs Cycle
How many energy-producing molecules do we have per 1 glucose molecule?
Intermediate step: Pyruvate oxidation
1 NADH x2= 2 NADH
Krebs Cycle:  3 NADHx2= 6 NADH
1 ATPx2= 2 ATP
1 FADH2x2= 2 FADH2
+ 2 ATP, 2 NADH from glycolysis
Total: 4 ATP, 10 NADH, 2 FADH2 --> forms 38 ATP in the electron transport chain

20. Helpful links Khan Academy video- extremely helpful and simple
Salman, K. (Producer) (2009). Krebs / citric acid cycle [Web]. Retrieved from
Video that tracks the movement of the atoms during the various steps of the process. Very useful for precise information about how each molecule forms. Helpful for review
Bielecki, A. (Producer) (2011). The citric acid cycle (krebs cycle) [Web]. Retrieved from
 Flash Video
The citric acid cycle [Web]. (n/a). Retrieved from
Another instructional Video
Krebs cycle [Web]. (n/a). Retrieved from

21. Resources
“Alpha Ketoglutarate Dehydrogenase - Links Krebs Cycle to Amino Acid production” (2002). Retrieved from
Dax, R., H.A., D.B. (2010). From Pyruvate to Acetyl-CoA: Oxidation. Retrieved from
Diwan, J. J. (2007). Pyruvate Dehydrogenase and Krebs Cycle. Retrieved from
Edwards, C. (2010). Energy Production Through the Krebs Cycle. Retrieved from
Freeman, W.H. (2002). The Citric Acid Cycle. Retrieved from
Krebs cycle. (n.d.). Retrieved from

22. "Krebs Cycle." The Gale Encyclopedia of Science. Ed. K. Lee Lerner and Brenda Wilmoth Lerner. 3rd ed. Vol. 3. Detroit: Gale, Gale Virtual Reference Library. Web. 29 Oct
McGraw Hill Co. (n.d.). Animation: How the krebs cycle works [Web]. Retrieved from
Noiva, Robert. "Krebs Cycle." Chemistry: Foundations and Applications. Ed. J. J. Lagowski. Vol. 3. New York: Macmillan Reference USA, Gale Virtual Reference Library. Web. 29 Oct   
Rosenberg, H. I. (n.d.). Cellular respiration summary. Retrieved from
The citric acid cycle [Web]. (n/a). Retrieved from
“The Tricarboxylic Cycle.” (2003). Retrieved from
Tricarboxylic acid cycle. (2011). In Encyclopædia Britannica. Retrieved from