Krebs Cycle / Citric Acid / Tricarboxylic Acid Cycle (TCA)

Krebs Cycle or Citric Acid or Tricarboxylic Acid Cycle (TCA)

Hans Krebs discovered the cycle.  The cycle is also termed as citric acid cycle or tricarboxylic acid (TCA) cycle after the initial products.  The pyruvic acid formed during glycolysis enters mitochondria where it is further oxidised.

Following two steps of aerobic oxidation occur within mitochondria.

1.Formation of Acetyl coenzyme A.

2.Krebs cycle or citric acid or tricarboxylic acid cycle (TCA).

Formation of Acetyl Coenzyme A:

Pyruvic acid molecules that are produced during glycolysis move into mitochondria. All the reactions of cellular respiration take place within these tiny power houses.  Here each three carbon molecule of pyruvic acid is decarboxylated and dehydrogenated.  Due to release of carbon dioxide, 3 carbon molecule of pyruvic acid thus converts into a 2 carbon acetyl group. This 2 carbon acetyl group thus reacts with a large complex enzyme, termed as coenzyme A.  As a result, a compound termed as, Acetyl coenzyme A (CoA) is formed.  Thus the process requires five cofactors namely, magnesium (mg++) thiamine pyrophosphate (TPP), NAD, coenzyme A and lipoic acid.  Following is the overall reaction of conversion of pyruvic acid into Acetyl coenzyme A :

2 Pyruvic acid+2 CoA+2 NAD →2 Acetyl CoA+2 NADH+2H+

Thus, each molecule of pyruvic acid (3 carbon compound) forms one molecule of carbon dioxide (1 carbon compound) and one molecule of Acetyl coenzyme A (2 carbon compound).  Thus the NADH2 molecule formed in this process enters the electron transport system of mitochondria to release energy.

Krebs cycle or Citric acid cycle or TCA cycle:

The reactions of these cycles were worked out by Sir. Hans Krebs, hence, the name Krebs cycle.  Following are the important steps of Krebs cycle:

Condensation (Formation of citric acid):

Oxaloacetic acid accepts acetyl group of the acetyl coenzyme A and thus forms citric acid in the presence of enzyme, citrate synthetase.

Oxaloacetic acid + Acetyl Co A + H2O→Citric acid+CoA

 Dehydration (Formation of cis-aconitic acid):

Citric acid (6 carbon compound) by losing one molecule of water changes into another 6 carbon compound cis-aconitic acid in the presence of enzyme, aconitase.

Citric acid →Cis-aconitic acid+H2O

Hydration (Formation of iso-citric acid):

Cis-aconitic acid thus converts to iso-citric acid by utilizing water in the presence of enzyme, aconitase.

Cis-aconitic acid+H2O→Iso-citric acid

Dehydrogenation (Formation oxalosuccinic acid):

Iso-citric acid on oxidation gives rise to another 6 carbon compound oxalosuccinic acid. The reaction also requires an enzyme, iso-citrate dehydrogenase.  The two hydrogen atoms that are removed in this process are then accepted by NAD.

Iso-citric acid+NAD→Oxalosuccinic acid+NADH2

Decarboxylation (Formation of α-ketoglutaric acid):

This step involves decarboxylation of oxalosuccinic acid.  As a result, it leads to the formation of a 5 carbon compound, α-ketoglutaric acid .  The reaction takes place with the help of an enzyme, i.e., decarboxylase.

Oxalosuccinic acid→α-ketoglutaric acid+CO2

Dehydrogenation and Decarboxylation (Formation of succinyl CoA):

In this step oxidative decarboxylation of α -ketoglutaric acid occurs.  As a result, it leads to the formation of a 4 carbon compound i.e., succinyl CoA.  This reaction also requires an enzyme, α-ketoglutarate dehydrogenase.  Thus in this step, one molecule of NAD reduces to NADH2 and one molecule of CO2 is released.

α-ketoglutaric acid+CoA→Succinyl CoA+CO2+NADH2

Formation of succinic acid and ATP/GTP:

In this step, coenzyme A splits off from succinyl CoA.  As a result it leads to the formation of  succinic acid in the presence of enzyme, succinyl thiokinase.  In this process, one molecule of GTP is formed, which later gives one molecule of ATP.  This reaction is also referred to as substrate phosphorylation.

Succinyl CoA+GDP+H3PO4+ H2O→Succinic acid+GTP+CoA


Dehydrogenation (Formation of fumaric acid):

Oxidation of succinic acid results in the formation of fumaric acid.  The reaction also requires an enzyme i.e., succinate dehydrogenase.  As a result two hydrogen atoms are released, which are picked up by the hydrogen carrier molecules i.e., FAD (flavin adenine dinucleotide).

Succinic acid+FAD→Fumaric acid+FADH2

Hydration (Formation of malic acid):

With the addition of water, fumaric acid is converts into malic acid. This reaction also requires an enzyme, fumarase.

Fumaric acid+H2O→Malic acid

Dehydrogenation (Regeneration of oxaloacetic acid):

In the last step of Krebs cycle, oxidation of malic acid regenerates oxaloacetic acid in the presence of enzyme, malate dehydrogenase.

Malic acid+NAD→Oxaloacetic acid+ NADH2

Oxaloacetic acid picks up another molecule of activated acetate to repeat the cycle.  A molecule of glucose yields two molecules of NADH2, 2 ATP and 2 pyruvate while undergoing glycolysis.  In Krebs cycle there is a complete degradation of 2 molecules of pyruvate to form 2 molecules of ATP, 8 NADH2 and 2 FADH2.

Schematic representation of Krebs cycle or TCA cycle or Citric acid cycle

Fig: Schematic representation of Krebs cycle or TCA cycle or Citric acid cycle

Difference between Krebs Cycle and Glycolysis

Following are the differences between Krebs cycle and Glycolysis :

                       Krebs Cycle                   Glycolysis
1.  It is a cyclic pathway. 1.  It is a linear pathway.
2.  Krebs cycle occurs inside mitochondria. 2.  It occurs inside cytoplasm.
3.  It occurs only in aerobic respiration. 3.  Glycolysis is common to both aerobic and  anaerobic modes of respiration
4.  Krebs cycle is the second step in respiration where an active acetyl group is broken down completely. 4.  Glycolysis is the first step of respiration in which glucose is broken down to the level of pyruvic acid.
5.  It degrades pyruvate or pyruvic acid completely into inorganic substances (i.e., CO2+H2O). 5.  It degrades one molecule of glucose into two molecules of organic substance (i.e., pyruvic acid).
6.  It does not consume ATP. 6.  It consumes two molecules of ATP for the initial phosphorylation of substrate molecule.
7.  In Krebs cycle, two acetyl residues liberate two ATP molecules through substrate level phosphorylation. 7.  In Glycolysis, one glucose molecule liberates four ATP molecules through substrate level phosphorylation.
8.  It produces six molecules of NADH2 and also two molecules of  FADH2 for every two molecules of Acetyl CoA oxidised by it.  It again liberates two molecules of NADH2 during the conversion of two pyruvates to Acetyl Co A 8.  Net gain is two molecules of NADH2 and also two molecules of ATP for every molecule of glucose broken down.
9.  The net gain of energy is equal to 24 molecules of ATP. 9.  The net gain of energy is equal to 8 molecules of ATP.
10.  There is evolution of CO2 in Krebs cycle. 10.  There is no evolution of CO2.