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The Krebs Cycle - A Biochemistry Viewpoint -

A look into the chemistry behind the Krebs cycle

Ellen Brookes

on 4 April 2011

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Transcript of The Krebs Cycle - A Biochemistry Viewpoint -

The Krebs Cycle
~ A Biolchemistry Viewpoint ~ Who was Krebs? What is the Krebs cycle? A cycle? Complex Substances The Processes What biology tells us about the Krebs cycle he Krebs cycle (or the Tricarboxylic Acid Cycle/Citric Acid Cycle) is a form of cell respiration. Respiration is an exothermic reaction that occurs within the body to change Oxygen and fuel molecules (e.g food) to water, Carbon Dioxide and energy. thdiunaipr
The simple equation for Respiration is
C6H12O6+ 6O2 --> 6O2 + 6H2O + energy (GTP)
The cycle is considered 'aerobic' which means that is must be done in the presence of Oxygen (which will be used during the process).

Glucose (C6H12O6) can be obtained in many ways in a person's diet - through complex carbohydrate molecules (which are made up of multiple glucose molecules joined together) , fatty acids and amino acids which contain Carbon, Hydrogen and Oxygen atoms, like glucose, but in very different ratios.
The overall reaction happens in eight 'steps'.

As the cycle begins with a reaction between Acetyl-CoA and a four carbon chain oxaloacetate, how did we get these substances?
Acetate (acquired from an earlier reaction in glycolysis) reacts with an enzyme called coenzyme A. This reactions yields Acetyl-CoA, and from here, the Krebs Cycle begins

Step 1.The Acetyl-CoA combines with the Oxaloacetate (the process for obtaining is revealed later in the cycle) to form a molecule called Citrate. After this step, the coenzyme undergoes hydrolysis (addtion of a water molecule), releasing it so that it may be used to combine with acetate and begin the cycle again.

Step 2. The Citrate molecule is then subjected to isomerization. A Hydroxyl group (OH-) and an H+ molecule are removed in the form of water and two carbon molecules form a double bond until the water molecule is added back, only this time they are reversed in comparison to the original structure. This forms Isocitrate.

Step 3. The Isocitrate molecule is oxidized by an NAD molecule (see complex substances section) which is reduced by the H+ atom and Hydroxyl group. The NAD binds with a Hydrogen atom and carries another Hydrogen atom, leaving behind an intermediate Carbonyl group. Because this structure is incredibly unstable, a molecule of CO2 is also released, creating Alpha-Ketoglutarate.

Step 4. Coenzyme A returns to oxidise the Alpha-Ketoplutarate molecule. Decarboxylartion occurs, meaning another molecule of CO2 is released, with the help of an NAD molecule which is reduced once again to form NADH. When the CO2 is removed, a thioester bond forms between Alpha-Ketoglutarate and Coenzyme A, resulting in Succinyl-Coenzyme A.

Step 5. Hydrolysis occurs to (a water molecule releases its Hydrogen atoms to) Conenzyme A followed by a free-floating phosphate group displacing Coenzyme A and bonding with the Succinyl complex. The phosphate then transfers itself to a molecule of GDP to synthesize a molecule of GTP (see complex substances section) leaving behind a molecule of Succinate.

Step 6. Succinate is oxidised by an FAD molecule (see complex substances section). This means that the FAD 'steals' two Hydrogen atoms from Succinate and forces two Carbon atoms to form a double bond, creating Fumarate and releasing FADH2.

Step 7. Water is added to Fumarate in the form of a Hydrogen atom and a Hydroxyl group. The Hydrogen atom is added next to Carbon atom, while the OH- group is added to a Carbon next to a 'terminal' Carbonyl group; thus yielding a substance called Malate.

Step 8. Finally, the Malate molecule is oxidized by an NAD molecule and the Carbon that carried the Hydroxyl group is converted into a Carbonyl group. The end product is a regenrated Oxaloacetate (the same substance we started with), which can then be re-used to start the cycle again.

In conclusion, the overall equation looks something like this:
Acetyl-CoA + Oxaloacetate + 3NAD+ + GDP + Pi + FAD --> Oxaloacetate + 2CO2 + FADH2 + 3 NADH + 3H+ + GTP

This means that one cycle yields 2 molecules of CO2, 3 molecules of NADH, 1 molecule of FADH2 and one molecule of GTP - as well as the rejuvenated Oxaloacetate and 3 H+ molecules.
Pi stands for the inorganic phosphate group in Step. 5 NAD - Nicotinamide Adenine Dinuleotide (C21H27N7O12P2) oxidizes mostly Carbon-Oxyden bonds.
GTP - Guanosine Triphosphate (C10H16N5O14P3) the useable form of chemical energy produced by respiration.
FAD - Flavoadenine (C27H31N9O15P2)
oxidizes carbon-carbon double and triple bonds. The Krebs cycle is considered a cycle because the reactants at the beginning are rejuvenated throughout the process and can then be re-used to begin the cycle again. Also, it must be a cycle as a person keeps breathing and eating without too much hassle. Hans Adolf Krebs was a German biochemist, who discovered the 'Krebs Cycle' in 1937. This and his other works in the field of cellular metabolism won him the Nobel Prize for Physiology (Medicine) in 1953. Bibliography Step One Step Two Step Three Step Four Step Five Step Six Step Seven Step Eight Molecule Reaction type Reactants/Coenzymes Products/Coenzymes
I. Citrate Dehydration H2O
I/II. cis-Aconitate Hydration H2O
II. Isocitrate Oxidation NAD+ NADH + H+
II/III. Oxalosuccinate Decarboxylation
III. α-Ketoglutarate Oxidative decarboxylation NAD+ +CoA-SH NADH + H+ + CO2
IV. Succinyl-CoA Hydrolysis GDP + Pi GTP + CoA-SH
V. Succinate Oxidation FAD FADH2
VI. Fumarate Addition (H2O) H2O
VII. L-Malate Oxidation NAD+ NADH + H+
VIII. Oxaloacetate Condensation Another useful site (animation):, 2007, Biology-Online Dictionary, viewed 30 March, 2011

Canaday, M. 2002, The Krebs Cycle, viewed 31 March, 2011, 2007, Citric acid cycle, viewed 30 March, 2011

Dubroff, M. D, 2011, What is the Krebs Cycle?, viewed 31 March, 2011

Helmenstein, A. M, Citric Acid Cycle, viewed 30 March, 2011

Silva, P. 2002, The chemical logic behind… the citric acid cycle, viewed 30 March, 2011

Sparknotes LLC, 2009, Cell Respiration: Introduction, viewed 28 March, 2011,

Sparknotes LLC, 2009, Cell Respiration, viewed 28 March, 2011

Sparknotes LLC, 2009, Cells: SparkCharts, viewed 28 March, 2011,

Sparknotes LLC, 2009, I-L, viewed 28 March 2011,

Sparknotes LLC, 2009, The Citric Acid Cycle, viewed 28 March, 2011,

Sparknotes LLC, 2009, The Reactions of the Citric Acid Cycle, viewed on 28 March, 2011,

Teachers' Domain, 2003, Krebs Cycle, viewed 31 March, 2011

Images/Tables/Videos, 2007, Citric acid cycle, viewed 30 March, 2011

Essential Cell Biology, 3rd Edition (video recording), Alberts, Bray, Hopkin, Johnson, Lewis, Raff, Roberts, & Walter, 2009, viewed 31 March, 2011 (at

Helmenstein, A. M, Citric Acid Cycle, viewed 30 March, 2011

Http://, 2003, Sir Hans Adolf Krebs, viewed 31 March, 2011,

Kent, G. 2004, krebstca, viewed 28 March, 2011,

Sparknotes LLC, 2009, The Reactions of the Citric Acid Cycle, viewed on 28 March, 2011, By Ellen Brookes
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