Pyruvate Oxidation and Krebs
Cycle
Jennifer
Agnes
Hilary
Lucy
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.
Glycolysis
REMEMBER: After Glycolysis which takes place in
the cytosol, all the steps take place in the
mitochondria
Depending on the presence of oxygen, the pyruvate will
either enter a fermentation process (lactic acid or alcohol) or
proceed towards the Krebs Cycle.
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
o proteins, lipids, can also be broken down into acetyl CoA
o can produce fat or ATP, depending on ATP levels in the
cell
Pyruvate Oxidation
• net production:
o 2 NADH - electron transport chain
o 2 acetyl-CoA - enter Krebs Cycle
o 2H+ - dissolves in matrix
o 2 CO2 - diffuses out of cell
2 pyruvate + 2 NAD + 2 CoA
-> 2 acetyl-CoA + 2 NADH + 2H2+ 2 CO2
Pyruvate Oxidation
- transition step between
glycolysis and Kreb's Cycle
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
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
Krebs Cycle Equation
Oxaloacetate + Acetyl-CoA+ ADP + Pi +3NAD+ + FAD
-->
CoA+ATP+3NADH +3H++FADH2+ 2CO2+ Oxaloacetate
Krebs Cycle: The Simple Version
Also known as the citric or tricarboxylic acid cycle
(TCA) because citric acid has THREE CARBOXYL
groups
Hans Krebs
(1900-1981)
•
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.
http://rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/krebscyc/krebscyc.htm
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)
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
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
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
Helpful links
Khan Academy video- extremely helpful and simple
Salman, K. (Producer) (2009). Krebs / citric acid cycle [Web]. Retrieved from
http://www.youtube.com/watch?v=juM2ROSLWfw
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
http://youtu.be/7gR4s8ool1Y
Flash Video
The citric acid cycle [Web]. (n/a). Retrieved from
http://www.wiley.com/college/pratt/0471393878/student/animations/citric_acid_cycle/index.
html
Another instructional Video
Krebs cycle [Web]. (n/a). Retrieved from http://youtu.be/O6bInBQXtmM
Resources
“Alpha Ketoglutarate Dehydrogenase - Links Krebs Cycle to Amino Acid production” (2002). Retrieved from
http://everything2.com/title/Alpha+Ketoglutarate+Dehydrogenase++Links+Krebs+Cycle+to+Amino+Acid+production
Dax, R., H.A., D.B. (2010). From Pyruvate to Acetyl-CoA: Oxidation. Retrieved from
http://library.thinkquest.org/11226/main/c05txt.htm
Diwan, J. J. (2007). Pyruvate Dehydrogenase and Krebs Cycle. Retrieved from
http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/krebs.htm
Edwards, C. (2010). Energy Production Through the Krebs Cycle. Retrieved from
http://drchadedwards.com/244/energy-production-through-the-krebs-cycle/
Freeman, W.H. (2002). The Citric Acid Cycle. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK21163/
Krebs cycle. (n.d.). Retrieved from
http://cmapspublic2.ihmc.us/rid=1292768176697_195977725_68466/krebs_cycle.cmap
"Krebs Cycle." The Gale Encyclopedia of Science. Ed. K. Lee Lerner and Brenda Wilmoth Lerner. 3rd ed.
Vol. 3. Detroit: Gale, 2004. 2249-2251. Gale Virtual Reference Library. Web. 29 Oct. 2011.
McGraw Hill Co. (n.d.). Animation: How the krebs cycle works [Web]. Retrieved from
http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter25/animation__how_the_krebs_cycle_works__quiz_1_.ht
ml
Noiva, Robert. "Krebs Cycle." Chemistry: Foundations and Applications. Ed. J. J. Lagowski. Vol. 3. New
York: Macmillan Reference USA, 2004. 11-13. Gale Virtual Reference Library. Web. 29 Oct. 2011.
Rosenberg, H. I. (n.d.). Cellular respiration summary. Retrieved from
http://people.ucalgary.ca/~rosenber/CellularRespirationSummary.html
The citric acid cycle [Web]. (n/a). Retrieved from
http://www.wiley.com/college/boyer/0470003790/animations/tca/tca.htm
“The Tricarboxylic Cycle.” (2003). Retrieved from
http://web.virginia.edu/Heidi/chapter20/chp20.htm
Tricarboxylic acid cycle. (2011). In Encyclopædia Britannica. Retrieved from
http://www.britannica.com/EBchecked/topic/604852/tricarboxylic-acid-cycle