TCA cycle

Amphibolic role in citric acid cycle:

The TCA cycle functions not in the oxidative catabolism of carbohydrates, fatty acids, and amino acids but also has an active role in many biosynthetic pathways for which it provides precursors. The role of TCA cycle in other biosynthetic processes are mentioned below:

1. Synthesis of carbohydrates:

In the presence of excess succinate, a portion of it is converted to pyruvate by enzyme pyruvate decarboxylase. Pyruvate is then converted to carbohydrate by reverse EMP pathway.

2. Synthesis of lipid:

Acetyl CoA is the key intermediate in the biosynthesis of lipids.

3. Synthesis of proteins:

Citric acid cycle provides a means of generation of non- essential amino acids in animals. Two of these amino acids are obtained directly from the intermediates of TCA cycle. Alanine is directly made from pyruvate. Glutamate is made directly from α-keto glutarate by cells. Aspartate is made from oxaloacetate.

4. Synthesis of pyrimidines and purines:

Purines and pyrimidines are important constituents of the co-enzymes and nucleic acid. Aspartate provides the carbon skeleton of pyrimidine whereas the glycine from pyruvate contributes to the carbon skeleton for purines.

5. Synthesis of porphyries:

Porphyrins are essential components of respiratory pigments and enzymes. Animals utilize succinyl-CoA as one of the compounds for the synthesis of porphyrins.

1. TCA cycle is an amphibolic pathway: an amphibolic pathway is defined as the pathway where both catabolic and anabolic process occurs. TCA cycle is an amphibolic pathway, both catabolic and anabolic process occurs in this pathway. Catabolism is the process in which complex molecules break down into simpler molecules combines to form complex molecules.

In TCA cycle, both catabolism and anabolism process occurs. For eg., acetyl CoA which is a 2c compound combines with oxaloacetic acid, the 4c compound to form citric acid which is 6-carbon compound. This is an anabolic process. Similarly a 6c compound, α-ketoglutaric acid is formed which is a catabolic process. In this catabolic and anabolic process NADH, FADH₂ and GTP are produced which enters. In the electron transport chain which finally, results in the production of ATP.

Tricarboxylic acid cycle(TCA, Krebs's cycle):

→ Pyruvic acid, the end product of glycolysis does not enter the citric acid cycle.

→ The 3 carbon atom molecules of pyruvate is the first charge into two carbon atom acetic acid. One carbon is released as CO₂.

→ Acidic acid on existing the mitochondrial units with CoA to form acetyl CoA. This reaction is catalyzed by several enzymes collectively known as pyruvate dehydrogenase. Pyruvate is oxidized to acetyl-CoA which then undergoes a series of changes refer to as Krebs's cycle. It is also called as TCA cycle since citric acid is a tricarboxylic acid (with the 3-COOH group). TCA cycle was first given by H.A Krebs.

The cycle occurs in all aerobic organisms and leads to complete oxidation of glucose to CO₂ and water. While glycolysis leads to incomplete oxidation of glucose to pyruvate. TCA cycle completely oxidizes it to release a large amount of energy in a form of NADH+H⁺ mainly on GTP. NADH+H⁺ enter the respiratory chain where each NADH+H⁺ produces 3 ATP molecules. GTP is converted to ATP by substrate level oxidation. Another form of energy is in the form of FADH₂ which also enters the respiratory chain to form two molecules of ATP. All the reactions of TCA cycle take place in the inner compartment of mitochondria.

Reactions of TCA cycle

1. Formation of citrate: the first step in this cycle is the condensation of acetyl-CoA with oxaloacetate to form citrate catalyzed by citrate synthetase.
2. Formation of isocitrate via. Aconitate: isocitrate is the isomeric form of citrate which is formed via (through) aconitate followed by dehydration and hydration reactions. First of all, citrate is followed by hydration to form isocitrate by the same enzyme aconitase.
3. Dehydrogenation first: Isocitrate undergoes dehydrogenation in the presence of enzyme isocitrate dehydrogenase to form Oxalosuccinate. The pair of the hydrogen atom is accepted by NAD⁺ to form NADH+H⁺.
4. Decarboxylation: Oxalosuccinate undergoes decarboxylation to form α-ketoglutarate with the enzyme decarboxylase.
5. Oxidation of α-ketoglutarate: the next step is oxidation decarboxylation of α-ketoglutarate to form succinate-CoA and by the action of enzyme α-ketoglutarate dehydrogenase complex. NAD⁺ serve as electron acceptors and CoA as the carrier of succinyl group.
6. Conversion of succinyl-CoA to succinate: succinyl-CoA is converted to succinate by the enzyme succinyl-CoA synthetase (thiokinase). This reaction is coupled with phosphorylation of GDP to GTP.
7. Oxidation of succinate to fumarate: succinate formed from succinyl-CoA is oxidized to fumarate by the enzyme succinate dehydrogenase. In this reaction, FAD acts as hydrogen atom acceptor.
8. Hydration of fumarate to malate: fumarate is hydrated to form malate, the reactions are catalyzed by the enzyme fumarase.
9. Oxidation of malate to oxaloacetate: in the final reaction dehydrogenase catalyzes the oxidation of malate to oxaloacetate which is thus regenerated.

Significance

1. Kreb cycle completely oxidizes pyruvate into CO₂ with the release of a large amount of energy.
2. Beside oxidizing pyruvate Krebs cycle is also provide intermediate for the synthesis of another biomolecule α-keto glutarate use for synthesis for non-essential amino acid; malate citrate is used for formation of glucose. Therefore, Krebs cycle is considered as amphibolic pathway(both catabolic and anabolic pathway).

References

Arvind, Keshari K. and Kamal K Adhikari. A Textbook of Biology. Vidyarthi Pustak Bhander.

Michael J.Pleczar JR, Chan E.C.S. and Noel R. Krieg. Microbiology. Tata Mc GrawHill, 1993.

Powar. and Daginawala. General Microbiology.

Rangaswami and Bagyaraj D.J. Agricultural Microbiology.