Pharma gyan Pandit

Krebs cycle

 It is given by Hans Krebs in the 1930s.  The cycle has other names as well, after the names of some of the types of components in the cycle like citric acid cycle, tricarboxylic acid cycle as identify citric acid and tricarboxylic acids in the pathway.

 Glycolysis only releases 1/4 of the chemical energy stored in glucose.  If oxygen is present, the pyruvate produced from glycolysis enters the mitochondrion where the enzymes of the Krebs cycle complete the oxidation.

Preparation for the Krebs cycle

Pyruvate doesn’t enter the Krebs cycle directly.  First it is oxidized and combined with a carrier molecule, coenzyme A. 

 pyruvate + NAD⁺ + coenzyme A ---->  acetyl CoA + CO₂ + NADH + H⁺

            (1)  pyruvate is transported into the mitochondrion

            (2)  pyruvate is oxidized to a 2 C compound (acetate) with loss of CO₂

            (3) the acetate is linked to coenzyme A, forming acetyl CoA

            (4)  NAD⁺ is reduced in the reaction to form NADH + H⁺

The conversion of pyruvate (3 C) to acetyl CoA (2 C).  In the Krebs cycle, the two carbons from acetyl CoA are passed to a 4C compound oxaloacetate and then through a series of intermediates.  These reactions take place in the matrix of the mitochondrion.  Ultimately, two carbons are released as carbon dioxide by the reactions of the Krebs cycle.  

Other key products of the Krebs cycle result in capturing the chemical energy of the oxidized sugars in forms that the cell can use.

One “turn” of the Krebs cycle produces

            (1)  two molecules of carbon dioxide

            (2)  3 NADH + H⁺

            (3)  1 FADH₂ (an electron carrier like NAD⁺, which is derived from the B vitamin, riboflavin)

            (4)  1 ATP by substrate level phosphorylation

 Many more molecules of ATP are ultimately produced when the NADH + H⁺ and the FADH₂ are oxidized in the electron transport chain. 

Key steps 

1.  Acetyl CoA joins the Krebs cycle by transfering acetate to the compound oxaloacetate, forming citrate.
2. When isocitrate is converted to a-ketoglutarate, one CO₂ is released and one NAD⁺ is reduced to give NADH + H^+.
3. More CO₂ and NADH + H⁺ are formed in the very next step as a-ketoglutarate is further oxidized. 
4. Substrate level phosphorylation occur at step 5 in the pathway, the conversion of succinyl CoA to succinate.
5. FADH₂ is formed in the redox reaction where succinate is oxidized to give fumarate.
6.  A third NADH + H⁺ is formed during the oxidation of malate to give oxaloacetate.

 The cycle can then begin again by the addition of two more carbons from acetyl CoA.

NET products per turn

-        2 CO₂

-        3 NADH + 3H⁺

-        1 FADH₂

-        1 ATP

NET products per glucose

-        4 CO₂

-        6 NADH + 6H⁺

-        2 FADH₂

-        2 ATP