Kreb's Cycle(TCA Cycle)

CHAPTER: 11(C)

Kreb’s Cycle (TCA Cycle)

Kreb’s Cycle (TCA Cycle/ Citric Acid Cycle):

Ø  TCA cycle is most important metabolic pathway for the energy supply to the body. About 65.70%  of the ATP is synthesized by this cycle.

Ø  TCA cycle essentially  involves the oxidation of acetyl-CoA to CO₂& H₂O .

Ø  This cycle utilizes about 2/3 of total oxygen consumed by the body.

Ø  The name TCA cycle is used , since at the outset of the cycle , tricarboxylic acids (citrate, isocitrate , cis-aconitate) paticipate.

Ø  Common oxidative pathway for carbohydrates, fats & amino acids.

Ø  Most important central pathway connecting almost all the individual metabolic pathways either directly or indirectly.

Ø  Enzymes for TCA cycle are located in mitochondrial matrix in close proximity to the electron transport chain.

Ø  TCA cycle basically involves the combinition of 2-C Acetyl CoA with 4-C Oxaloacetate to produce 6-C Citrate.

•      In this rxn. 2-Cs are oxidised to CO₂& oxaloacetate is regenerated & recycled.

•      Oxaloacetate is considered to play a catalytic role in citric acid cycle.

Steps involved in TCA cycle:

1. The first reaction of the citric acid cycle is catalyzed by the enzyme citrate synthase. In this step, oxaloacetate is joined with acetyl-CoA to form citric acid. Once the two molecules are joined, a water molecule attacks the acetyl leading to the release of coenzyme A from the complex.
   
2. The next reaction of the citric acid cycle is catalyzed by the enzyme acontinase. In this reaction, a water molecule is removed from the citric acid and then put back on in another location. The overall effect of this conversion is that the –OH group is moved from the 3' to the 4' position on the molecule. This transformation yields the molecule isocitrate.
   

3. Two events occur in reaction 3 of the citric acid cycle. In the first reaction, we see our first generation of NADH from NAD. The enzyme isocitrate dehydrogenase catalyzes the oxidation of the –OH group at the 4' position of isocitrate to yield an intermediate which then has a carbon dioxide molecule removed from it to yield alpha-ketoglutarate.
   
4. In reaction 4 of the citric acid cycle, alpha-ketoglutarate loses a carbon dioxide molecule and coenzyme A is added in its place. The decarboxylation occurs with the help of NAD, which is converted to NADH. The enzyme that catalyzes this reaction is alpha-ketoglutarate dehydrogenase. The mechanism of this conversion is very similar to what occurs in the first few steps of pyruvate metabolism. The resulting molecule is called succinyl-CoA.
   

5. The enzyme succinyl-CoA synthetase catalyzes the fifth reaction of the citric acid cycle. In this step a molecule of guanosine triphosphate (GTP) is synthesized. In this reaction, a free phosphate group first attacks the succinyl-CoA molecule releasing the CoA. After the phosphate is attached to the molecule, it is transferred to the GDP to form GTP. The resulting product is the molecule succinate.
   
6. The enzyme succinate dehydrogenase catalyzes the removal of two hydrogens from succinate in the sixth reaction of the citric acid cycle. In the reaction, a molecule of FAD, a coenzyme similar to NAD, is reduced to FADH2 as it takes the hydrogens from succinate. The product of this reaction is fumarate.
   
7. In this reaction, the enzyme fumarase catalyzes the addition of a water molecule to the fumarate in the form of an –OH group to yield the molecule L- malate.
   
8. In the final reaction of the citric acid cycle, we regenerate oxaloacetate by oxidizing L–malate with a molecule of NAD to produce NADH.
   

Significance of TCA Cycle:

Ø  Total oxidation of carbohydrates, lipids & fats.

Ø  Produces different compound that are needed for the body.

Ø  Produces energy in the form of ATP.

Ø  It does not take place during hypoxic condition.