Pyruvate Oxidation and Krebs Cycle

JenniferAgnesHilaryLucy

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 metabolismo 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 chaino 2 acetyl-CoA - enter Krebs Cycleo 2H+ - dissolves in matrixo 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.htmInteractive Krebs Cycle (with enzyme names)

Step1: Acetyl+Oxaloacetate= CitrateCoA-SH freedEnzyme:  Citrate Synthase

Step 2: Citrate rearranged to isocitrateEnzyme:Aconitase

Step 3: Oxidative decarboxylation: Loss of 2 H atoms to NAD+ (forms NADH + H+), removal of C as CO2,  isocitrate becomes a-ketoglutarateEnzyme:  Isocitrate DH Step 4: Succinyl-CoA produced. Oxidative decarboxylation occurs againEnzyme:a-ketoglutarate DH (multi-enzyme complex)

 Step 5: ATP formed via substrate level phosphorylation, Succinyl- CoA becomes succinateEnzyme:  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 tothem?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 CycleHow many energy-producing molecules do we have per 1 glucose molecule?Intermediate step: Pyruvate oxidation1 NADH x2= 2 NADH Krebs Cycle:  3 NADHx2= 6 NADH1 ATPx2= 2 ATP1 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 reviewBielecki, A. (Producer) (2011). The citric acid cycle (krebs cycle) [Web]. Retrieved from http://youtu.be/7gR4s8ool1Y

 Flash VideoThe citric acid cycle [Web]. (n/a). Retrieved from http://www.wiley.com/college/pratt/0471393878/student/animations/citric_acid_cycle/index.html

Another instructional VideoKrebs 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.htmDiwan, J. J. (2007). Pyruvate Dehydrogenase and Krebs Cycle. Retrieved from http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/krebs.htmEdwards, 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.mcgraw-hill.com/sites/0072507470/student_view0/chapter25/animation__how_the_krebs_cycle_works__quiz_1_.html  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