What is the Citric Acid Cycle?
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 the Citric Acid Cycle and where does it take place in a cell?
The Citric Acid Cycle, also known as the Krebs Cycle or Tricarboxylic Acid (TCA) Cycle, is a series of enzyme-catalysed chemical reactions central to cellular respiration. It is the main process for releasing stored energy by completely oxidizing acetyl-CoA derived from carbohydrates, fats, and proteins. This vital metabolic pathway occurs in the mitochondrial matrix of eukaryotic cells.
2. What is the primary purpose of the Citric Acid Cycle in cellular respiration?
The main purpose of the Citric Acid Cycle is not to produce large amounts of ATP directly, but to generate high-energy electron carriers. Its primary functions are:
- To complete the oxidation of glucose by breaking down acetyl-CoA into carbon dioxide (CO₂).
- To capture the high-energy electrons from this process in the form of NADH and FADH₂.
- To produce one molecule of ATP (or GTP) per cycle through substrate-level phosphorylation.
3. What are the key products generated from one turn of the Citric Acid Cycle?
For each molecule of acetyl-CoA that enters the cycle, one complete turn generates the following key products:
- Two molecules of carbon dioxide (CO₂)
- Three molecules of NADH
- One molecule of FADH₂
- One molecule of ATP (or its equivalent, GTP)
4. Why is the Citric Acid Cycle considered an amphibolic pathway?
An amphibolic pathway is one that serves both catabolic (breaking down) and anabolic (building up) purposes. The Citric Acid Cycle is a prime example because:
- Catabolically, it breaks down acetyl-CoA to produce energy (NADH, FADH₂, ATP).
- Anabolically, its intermediates, such as citrate, α-ketoglutarate, and oxaloacetate, can be drawn off and used as precursors for the synthesis of fatty acids, amino acids, and glucose.
5. How is the Citric Acid Cycle regulated within the cell?
The Citric Acid Cycle is tightly regulated to match the cell's energy needs. Regulation occurs primarily at three irreversible enzyme-catalysed steps:
- Citrate Synthase: Inhibited by high concentrations of ATP, NADH, and succinyl-CoA.
- Isocitrate Dehydrogenase: Stimulated by ADP and inhibited by ATP and NADH.
- α-Ketoglutarate Dehydrogenase: Inhibited by its products, succinyl-CoA and NADH, as well as by high levels of ATP.
6. Can you list the eight main reactions or steps of the Citric Acid Cycle?
The Citric Acid Cycle is a sequence of eight main reactions:
- Formation of Citrate: Acetyl-CoA joins with oxaloacetate to form citrate.
- Isomerisation to Isocitrate: Citrate is converted into its isomer, isocitrate.
- Oxidation of Isocitrate: Isocitrate is oxidised, releasing CO₂ and forming α-ketoglutarate and NADH.
- Oxidation of α-Ketoglutarate: α-ketoglutarate is oxidised, releasing CO₂ and forming succinyl-CoA and NADH.
- Formation of Succinate: Succinyl-CoA is converted to succinate, producing GTP (or ATP).
- Oxidation of Succinate: Succinate is oxidised to fumarate, producing FADH₂.
- Hydration of Fumarate: Fumarate is converted to malate by the addition of water.
- Oxidation of Malate: Malate is oxidised to regenerate oxaloacetate, producing a final NADH molecule.
7. What happens to the NADH and FADH₂ produced during the Citric Acid Cycle?
The NADH and FADH₂ molecules produced in the Citric Acid Cycle are crucial electron carriers. They do not represent the final energy currency. Instead, they travel to the inner mitochondrial membrane to participate in the Electron Transport Chain (ETC). There, they donate their high-energy electrons, driving the process of oxidative phosphorylation, which is responsible for generating the vast majority of the cell's ATP.
8. How does the entry of acetyl-CoA link glycolysis to the Citric Acid Cycle?
Acetyl-CoA acts as the essential bridge connecting glycolysis and the Citric Acid Cycle. The process unfolds in these steps:
- Glycolysis occurs in the cytoplasm, breaking down one glucose molecule into two pyruvate molecules.
- Pyruvate is then transported into the mitochondrial matrix.
- Here, the enzyme pyruvate dehydrogenase complex converts each pyruvate molecule into an acetyl-CoA molecule in a reaction called the link reaction (or pyruvate oxidation).
- This newly formed acetyl-CoA is the starting substrate that enters the Citric Acid Cycle by combining with oxaloacetate.
