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7.2.2.2.2. Krebs cycle

Krebs cycle

The Krebs cycle (cycle citric acid or cycle of tricarboxylic acids) is a metabolic pathway, that is, a succession of chemical reactions, which is part of cellular respiration in all aerobic cells. In eukaryotic cells it is carried out in the mitochondrial matrix. In prokaryotes, the Krebs cycle occurs in the cytoplasm. 

In the Krebs cycle, a series of chemical reactions take place in which, in each of which, a specific enzyme intervenes, which lead to the total oxidation of acetyl-CoA to CO2. The electrons that are released in this oxidation are accepted by the coenzymes NAD+ and FAD, which are reduced in the form of NADH and FADH2 .  

The acetyl-CoA that is introduced into the cycle and is oxidized to CO 2 comes from the degradation of immediate principles , through the β-oxidation of fatty acids and the glycolysis of carbohydrates .

The Krebs cycle begins when the acetyl group of two carbons is combined with one molecule of four carbons ( oxaloacetic acid ) to produce a compound of six carbons  ( citric acid ). After going through this cycle, two of the six carbons are oxidized to CO 2 (removed) and the oxaloacetic acid is regenerated , making it available to bind again with another acetyl-CoA molecule . Therefore, two rounds of the cycle are necessary to fully oxidize a glucose molecule, since, in glycolysis , of each glucose molecule glucose formed two of pyruvic acid .

The energy that has been released by the oxidation of the carbon-hydrogen and carbon-carbon bonds is used to produce ATP ( one molecule per cycle ) from ADP , and to produce NADH from NAD + ( three molecules per cycle ) . It is also used to reduce another electron carrier, flavin adenine dinucleotide (FAD), obtaining FADH 2 molecule from FAD in each cycle.     

2 is not needed  directly in the Krebs cycle , since all electrons and protons released in carbon oxidation are accepted by NAD +  and FAD. However, oxygen is required in the electron transport chain , the next stage of respiration .

Therefore, the Krebs cycle is the metabolic (catabolic) route in which the total degradation of organic matter occurs to transform it into inorganic, obtaining energy directly (only 1 ATP per turn) or reoxidating the reduced coenzymes in the transport chain electron cells from the inner mitochondrial membrane .

Although the Krebs cycle is catabolic, some of its intermediate molecules can also be precursors to other anabolic processes that occur in the cytosol . That is why it is considered an amphibolic pathway  , that is, catabolic and anabolic at the same time .

Krebs cycle energy balance

At each turn of the cycle, the following is generated:

  • A molecule of GTP (convertible to ATP).
  • Three from NADH and one from FADH2. These molecules, by oxidative phosphorylation, will form ATP molecules  in the electron transport chain.
  • Two CO2 molecules, which correspond to the two carbons of a fully oxidized acetyl-CoA molecule. CO2 leaves the cell.

Therefore, in the Krebs cycle, from a glucose molecule (two rounds of the cycle), two GTP molecules are formed, six of NADH and two of FADH2. The GTP transfers its phosphate group to the ADP, while producing a molecule of ATP. Although the Krebs cycle does not have a great energy yield in the form of ATP, it does obtain reduced nucleotides from which you will obtain more ATP later.

Krebs cycle:

Acetyl-CoA + GDP + Pi + 3 NAD+ + FAD → 2 CO 2 + CoA + GTP + 3 NADH + FADH2

Questions that have come out in University entrance exams (Selectividad, EBAU, EvAU)

Madrid, June 2017, option A, question 5.

Regarding cell metabolism:

a) Briefly explain the meaning of the amphibole character of the Krebs Cycle. Indicate the initial and final products of that cycle (1.5 points).

b) State the role of the ATP molecule in cell metabolism (0.5 points).

Cantabria, July 2019, option 1, question 2.

Define the concept of "Krebs Cycle". Discuss its biological function in the cell. (1.5 points)

Castilla y León, July 2019, option A, question 3.

Related to cell metabolism:

a) List the initial molecules and the end products of glycolysis . (0,6)
b) Name three routes from which acetyl-CoA that is incorporated into the Krebs cycle can come. (0,3)
c) In which organelle and in what part of it does the Krebs cycle take place? List the coenzymes that originate at this stage and indicate their destination. (0.85)

Castilla La Mancha, June 2021, question 2.4.

In his Nobel Prize speech, Hans Krebs said: "... the citric acid cycle (of carbohydrate oxidation) also plays an important role in the stages after beta oxidation of fatty acids."

a. In which cell organelle and in which part of said organelle does the Krebs cycle take place?
b. What is the metabolic function of the Krebs cycle? List TWO of your final products.
c. In which molecule, which is incorporated into the Krebs cycle, does the oxidation of carbohydrates and fatty acids converge?
Justify your answer.

Fundamental ideas about the Krebs cycle

The Krebs cycle

  • The Krebs cycle is a metabolic pathway that is part of  cellular respiration  in all aerobic cells.
  • Energy is obtained from the oxidation of acetyl-CoA. proceeding comes from the degradation of immediate principles, through the β-oxidation of  fatty acids and the glycolysis of carbohydrates  and proteins, to CO2 and ATP.
  •  The acetyl group of two carbons is combined with one molecule of four carbons (oxaloacetic acid) to produce a compound of six carbons  (citric acid).     
    • After going through this cycle, two of the six carbons are oxidized to CO2 (removed) and the oxaloacetic acid is regenerated, making it available to bind again with another acetyl-CoA molecule. Therefore, two rounds of the cycle are necessary to fully oxidize a glucose molecule, since, in glycolysis two of pyruvic acid were formed from each glucose molecule.          
    • ATP is obtained  (one molecule per cycle)NADH (three molecules per cycle) and one FADH2 molecule in each cycle.   
    • You do not need O2 directly, although you do need O2 in the  electron transport chain, the next stage of respiration.
  • At each turn of the Krebs cycle, the following is generated:
    • A molecule of  GTP (convertible to ATP). 
    • Three from NADH and one from  FADH2 . 
    • Two CO2 molecules.
  • For each glucose molecule  (two rounds of the cycle), two GTP molecules are formed  , six of  NADH  and two of  FADH2 . 
  • Krebs cycle: Acetyl-CoA + GDP + Pi + 3NAD+ + FAD → 2CO2  + CoA +  GTP  + 3 NADH  +  FADH2