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# Citric Acid Cycle

## What is the Citric Acid Cycle?

Last updated date: 26th Mar 2023
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Citric acid is an organic compound of the chemical formula $C_{6}H_{8}O_{7}$. Hence it contains elements carbon, oxygen, and hydrogen. It is a white-colored solid and also a weak organic acid. Naturally, it is found in citrus fruits such as lemons, limes, etc. The citric acid cycle occurs in the metabolism of all aerobic organisms. Citric acid is an intermediate in the citric acid cycle in biochemistry. The molecule of citric acid has six atoms of carbon, seven oxygen atoms, and eight hydrogen atoms. It has a planar structure and three carboxylic acid groups (COOH) and a hydroxyl group (OH). The extended formula of it is $CH_{2}COOH-COHCOOH-CH_{2}COOH$.

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### Explanation of Citric Acid Cycle

The citric acid cycle (CAC) is also called the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle. In this cycle, the reaction involved is helpful to release the stored energy through the method of oxidation of acetyl-CoA which is derived from proteins, carbohydrates, and fats. However, this series of reactions is called the tricarboxylic acid (TCA) cycle, for the three carboxyl groups on its first two intermediates, or the Krebs cycle, after its discoverer, Hans Krebs. Hence this series of chemical reactions is important for all aerobic organisms to produce energy through the oxidation of acetate derived from fats, carbohydrates, and proteins into carbon dioxide ($CO_{2}$).

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The citric acid cycle occurs in the mitochondria and provides large amounts of energy in aerobic conditions by donating electrons to three NADH and one FADH (flavin adenine dinucleotide), which in order to create the proton gradient donate electrons to the chain of electron transport.

The citric acid cycle pathway is considered as a  major and also main metabolic pathway that connects the metabolism of carbohydrates, fat, and protein.  In the following article, simple citric acid cycle reactions are explained.

### Citric Acid Cycle Reactions

The citric acid cycle is an eight-step series of chemical reactions. These reactions include hydration reaction, redox reaction, dehydration reaction, and decarboxylation reactions. Adenosine triphosphate or Guanosine triphosphate is formed in each step of the citric cycle and also three molecules of NADH and one FADH2 molecule that helps in further steps. The eight reactions of the citric acid cycle with structures of each step of citric acid cycle reactions are given below.

• Reaction 1: Citrate synthase- In the first reaction of the citric acid cycle, the enzyme citrate synthase catalyzes the reaction. For the formation of the citric acid in the first step of the reaction, oxaloacetate is joined with acetyl-CoA. A water molecule attacks the acetyl once the two molecules are joined and leads to the release of coenzyme A from the complex.

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• Reaction 2: Aconitase- The enzyme aconitase is used as a catalyst in the next reaction. The water molecule is put back to a different location in this reaction by removing it from citric acid. The product yield is isocitrate from this transformation. The reaction is given below.

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• Reaction 3: Isocitrate Dehydrogenase- In the third reaction of the citric acid cycle, two events occur. In the first reaction, the generation of NADH from NAD takes place. The oxidation of the oxygen-hydrogen group is catalyzed by enzyme isocitrate dehydrogenase at the fourth position of isocitrate to get an intermediate which then has a carbon dioxide ($CO_{2}$) molecule removed from it to yield alpha-ketoglutarate. The reaction is given below.

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• Reaction 4: Alpha-ketoglutarate dehydrogenase- Alpha-ketoglutarate loses a carbon dioxide molecule in the fourth reaction of the cycle and coenzyme A is added in its place. With the help of NAD decarboxylation occurs, which is converted to NADH. The reaction is catalyzed by the enzyme alpha-ketoglutarate dehydrogenase. The molecule of the reaction formed at last is called succinyl-CoA.

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• Reaction 5: Succinyl-CoA Synthetase- A molecule of guanosine triphosphate (GTP) is synthesized in the fifth step of the reactions where it is catalyzed by the enzyme succinyl-CoA synthetase. With the addition of a free phosphate group to a GDP molecule, the GTP synthesis occurs. A free group of phosphate first attacks the succinyl-CoA molecule and releases the CoA. It is transferred to the GDP to form GTP after the phosphate is attached to the molecule. The resulting product is the molecule succinate. The reaction is as follows.

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• Reaction 6: Succinate Dehydrogenase- The enzyme succinate dehydrogenase catalyzes the reaction where it removes two hydrogens from succinate in the sixth reaction of the citric acid cycle. A molecule of FAD that is a coenzyme similar to NAD is reduced to $FADH_{2}$ in the reaction as it takes the hydrogens from succinate. The product of this reaction is fumarate. The reaction is given below.

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• Reaction 7: Fumarase- The second last reaction of this cycle is enhanced by the enzyme fumarase with the addition of an $H_{2}O$H2O molecule to the fumarate in the form of an –OH group to produce the molecule L- malate. The reaction is given below.

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• Reaction 8: Malate Dehydrogenase- Oxaloacetate is generated by oxidizing L–malate with a molecule of NAD to produce NADH in the last reaction of the citric acid cycle.

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### Do You Know?

The citric acid cycle was discovered by the chemist of Germany named Hans Adolf Krebs. He discovered this cycle in 1937 and marked a milestone in biochemistry. The Nobel Prize was given to him for his contribution to Physiology or Medicine in 1953.

### Conclusion

The citric acid cycle is an important catabolic pathway of oxidizing acetyl-CoA into $CO_{2}$ and generating ATP. The complex, as well as simple citric acid cycle reactions of the cycle, are carried out by eight enzymes that completely oxidize acetate. We got the information on the citric acid cycle through this article in detail.

## FAQs on Citric Acid Cycle

1. What is citric acid?

Citric acid has antioxidant properties, hence it is preferred to use as an excipient in the preparations of pharmaceuticals. It is very useful in controlling the pH as it is an acidulant and works as an anticoagulant by chelating Ca (calcium) in the blood. Its appearance is colorless, crystal, odorless with a taste of acid. It is denser than water. It is a tricarboxylic acid that bears at position two a hydroxy substituent as it is propane-1,2,3-tricarboxylic acid. It has different benefits for health as it improves kidney health, removes acne, etc, and is used for cleaning and removing dead skin as well.

2. Mention the products that are formed by the citric acid cycle?

The product obtained in a single turn of the citric cycle is formed when two carbons enter from acetyl COA, and two molecules of carbon dioxide are released, three molecules of NADH and one molecule of $NADH_{2}$ are produced, and one molecule of ATP and GTP is produced. Hence the three major molecules are generated in the citric acid cycle i.e. one molecule of NADH, one molecule of $FADH_{2}$, and one molecule of GTP(ATP) per acetyl-sCoA that enters the cycle. Thus, in total, from each round of the citric acid cycle, around ten molecules of adenosine triphosphate are produced.