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Tricarboxylic Acid Cycle – Overview, Stages, Roles, Significance

Last Updated : 29 Nov, 2022
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Plants respire throughout their lives because the plant cell requires energy to survive; however, plants breathe in a unique way known as cellular respiration. Photosynthesis is the process by which plants generate glucose molecules by capturing and converting sunlight energy. Several live experiments demonstrate plant respiration. All plants respire in order to provide energy to their cells, allowing them to be active or alive. 

Plants require oxygen to respire, and the process emits carbon dioxide. However, plants do have stomata (found in leaves) and lenticels (found in stems) that are actively involved in gas exchange. Plants lack specialized structures for gas exchange, in contrast to people and other creatures. Plant leaves, stems, and roots respire at a slower rate than other parts of the plant.

Tricarboxylic Acid Cycle 



  • The first compound of the cycle is citric acid, so the cycle is also known as the citric acid cycle. It is composed of three acids, so it is a tricarboxylic acid, and the cycle is also known as the tricarboxylic acid cycle.
  • It is an eight-step process in which the acetyl group of acetyl-CoA is oxidized to form two molecules of CO2 and one ATP is produced. NADH and FADH2 are also produced as reduced high-energy compounds.
  • Because each glucose molecule produces two molecules of acetyl-CoA, two turns of the Krebs cycle are required, yielding four CO2, six NADH, two FADH2, and two ATPs.
  • The respiratory substrate in the TCA cycle is acetyl coenzymeA, and the acceptor molecule is oxalic Acetic acid, a four-carbon compound.
  • This cycle consists of four dehydrogenation reactions (the removal of hydrogen) and two decarboxylation reactions (the removal of CO2). The formation of carbon dioxide will result from the reduction of coenzymes here.
  • Hans Krebs, the person who proposed the thorough cycle, is the name of the Krebs cycle. For his contribution, he received the Nobel Prize in 1953.
  • The citric acid cycle is a key metabolic pathway for the breakdown of carbohydrates, fats, and proteins. In aerobic conditions, the citric acid cycle occurs in mitochondria.
  • Carbohydrates, fats, and proteins are catabolized separately to form acetyl-CoA, which then enters the citric acid cycle.

Tricarboxylic acid cycle steps 

The citric acid cycle involves two major reactions:

  1. Acetyl-CoA formation
  2. Tricarboxylic acid cycle reactions 

Acetyl-CoA Formation 

  • Carbohydrates, fats, and proteins are catabolized by a separate pathway before entering the Krebs cycle.
  • For example, the enzyme Pyruvate dehydrogenase complex oxidizes pyruvate produced by aerobic glycolysis into acetyl-CoA and CO2.
  • In this reaction, one pyruvate molecule yields one NADH. This step connects glycolysis to the Krebs cycle.
  • It is an irreversible oxidative decarboxylation reaction that removes a molecule of carbon from pyruvate in the form of CO2.
  • It’s an eight-step procedure. The Krebs cycle takes place in the mitochondrial matrix when there are aerobic circumstances.

Tricarboxylic acid cycle reactions 

It’s an eight-step procedure. Under aerobic conditions, the Krebs cycle or TCA cycle occurs in the matrix of mitochondria.

Step 1. Citrate formation 

  • Coenzyme A is released in the first step, which is the condensation of acetyl CoA with the 4-carbon compound oxaloacetate to form 6C citrate. Citrate synthase catalyzes the reaction.
  • Oxaloacetate catalyzes the citric acid cycle and is regenerated at the end of the process.

Step 2. Isomerization of citrate to Isocitrate 

  • In the second step, citrate is converted to isocitrate, a citrate isomer. Citrate loses a water molecule and then gains one in this reaction to form isocitrate, which occurs in two steps.
  • Aconitase is an enzyme that catalyzes the isomerization of citrate to isocitrate via the intermediate cis-aconitate. This reaction is reversible.

Step 3. αlpha-ketoglutarate Formation 

  • In the second step, citrate is converted to isocitrate, a citrate isomer. Citrate loses a water molecule and then gains one in this reaction to form isocitrate, which occurs in two steps.
  • Aconitase is an enzyme that catalyzes the isomerization of citrate to isocitrate via the intermediate cis-aconitate. This reaction is reversible.

Step 4. Succinyl-CoA Formation 

  • alpha-ketoglutarate is oxidized here, reducing NAD+ to NADH and releasing a carbon dioxide molecule.
  • The remaining four-carbon molecules pick up CoA, forming the unstable compound succinyl CoA. The entire process is catalyzed by a-ketoglutarate dehydrogenase.

Step 5. Succinate Formation 

  • Succinate is formed by succinyl CoA. The reaction is catalyzed by the succinyl CoA synthase enzyme. Following this, GDP is phosphorylated at the substrate level to produce GTP. GTP phosphates ADP, which leads to the formation of ATP. In this step, a molecule of CO2 is released.

Step 6.Fumarate Formation 

  • Succinate is converted to fumarate through oxidation. FADH2 is created by transferring two hydrogen atoms to FAD.
  • Because the enzyme responsible for the reaction is embedded in the inner membrane of mitochondria, FADH2 transfers electrons directly to the electron transport chain.
  • The reaction is reversible.

Step 7. Malate formation 

  • The addition of one H2O converts fumarate to malate. Fumarase is the enzyme that catalyzes this reaction. This is a reversible hydration reaction.

Step 8. Formation and regeneration of oxaloacetate –

  • Malate is dehydrogenated to produce oxaloacetate, which combines with another acetyl CoA molecule to initiate the new cycle. The hydrogens that are removed are transferred to NAD+, where they form NADH.
  • The reaction is catalyzed by malate dehydrogenase.
  • This step regenerates oxaloacetate, which then combines with acetyl CoA to complete the cycle.

Significance of tricarboxylic acid cycle 

  • The tricarboxylic acid cycle is the final oxidation pathway for glucose, fats, and amino acids.
  • Amino acids (protein metabolic products) are deaminated and converted to pyruvate and other Krebs cycle intermediates. On deamination, they enter the cycle and are metabolized, for example, alanine is converted to pyruvate, glutamate to -ketoglutarate, and aspartate to oxaloacetate.
  • Fatty acids are -oxidized to produce acetyl CoA, which enters the Krebs cycle.
  • Many animals rely on nutrients other than glucose as a source of energy.
  • It is necessary for amino acid interconversion, gluconeogenesis, and lipogenesis.
  • It is the most important source of ATP production in cells. After complete nutrient oxidation, a large amount of energy is produced.

Roles of Tricarboxylic acid cycle

Role in Central metabolic pathway –

  • The TCA cycle is the final common metabolic pathway for carbs, fatty acids, and amino acids.
  • TCA is more efficient in terms of energy conservation than other metabolic pathways.
  • All of these biomolecules are first catabolized by their respective metabolic pathways to produce acetyl-CoA, which then enters the TCA cycle for further aerobic metabolism.

Tricarboxylic acid cycle is an aerobic process 

  • In the TCA cycle, NAD+ and FAD act as electron acceptors. The electron transport chain, which requires oxygen as the final electron acceptor, regenerates these. As a result, TCA and ETC are both aerobic processes.

Tricarboxylic acid cycle is an amphibolic pathway 

  • It participates in both catabolism and anabolism.

Anabolic role 

  • Because it provides precursors for the biosynthesis of other molecules in cells, TCA is an anabolic pathway.
  • Precursors for the biosynthesis of various molecules include citrate, -ketoglutarate, succinyl-CoA, and oxaloacetate.
  • SuccinylcoA is used in the synthesis of fatty acids and steroids.
  • Ketoglutarate is used to make some aminoacids, purine, and pyrimidine.
  • Oxaloacetate is used to make glucose, purine, and pyrimidine.

Catabolic role 

  • TCA is a catabolic pathway because it completely oxidizes acetyl-CoA into CO2 and H2O while releasing a large amount of energy.

Tricarboxylic acid cycle end products 

  • The conversion of succinyl CoA to succinate generates one ATP.
  • In the following reactions, 3 NAD+ are reduced to NADH and 1 FAD+ is converted to FADH2:

NADH Isocitrate to -ketoglutarate -ketoglutarate to succinyl CoA NADH Succinate to fumarate FADH2 Malate to Oxaloacetate NADH

  • Two molecules of CO2 are emitted. CO2 removal or citric acid decarboxylation occurs in two locations:

Isocitrate (6C) is being transformed into -ketoglutarate throughout this procedure (5C)
When -ketoglutarate (5C) is turned into succinyl CoA (4C)

  • Two cycles are needed for every glucose molecule because oxidative decarboxylation of two pyruvates results in the production of two acetyl CoA molecules.
  • Each NADH molecule can generate 1-2 ATPs upon oxidation in the electron transport chain, whereas each FADH2 molecule only generates 2 ATPs.
  • To summarise, the Krebs cycle produces 4 CO2, 6NADH, 2 FADH2, and 2 ATPs for the complete oxidation of a glucose molecule.

Frequently Asked Questions 

Question 1: What is the definition of the tricarboxylic acid cycle?


The TCA cycle is a series of chemical reactions that all aerobic organisms use to release stored energy by oxidizing acetyl CoA derived from carbohydrates, fats and proteins into ATP.

Question 2: What are the byproducts of the tricarboxylic acid cycle?


One Citric Acid cycle produces the following end products:

  • Two carbon dioxide molecules
  • Three NADH molecules, three hydrogen ions, and one FADH2 molecule
  • One GTP molecule

Question 3: What are the steps of the tricarboxylic acid cycle?


The TCA cycle is an eight-step pathway involved in the breakdown of organic molecules. Macromolecules such as glucose, sugars, fatty acids, amino acids, and so on cannot enter the TCA cycle directly. As a result, they must first be broken down into the two-carbon compound Acetyl CoA. After entering the TCA cycles, acetyl CoA undergoes additional chemical reactions that produce carbon dioxide and energy.

Question 4: Where does the TCA cycle take place?


Matrix of mitochondria.-The Krebs cycle occurs in all eukaryotes at the mitochondrial level. The cycle occurs in a mitochondrial matrix and generates chemical energy in the form of NADH, ATP, and FADH2. These are created by oxidizing the end product of glycolysis, pyruvate.

Question 5: Explain the steps in the tricarboxylic acid cycle that result in the formation of fumarate. ? 


Succinate is oxidized in this step to produce fumarate. In addition, two hydrogen atoms are transferred to FAD, resulting in FADH2. Because the enzyme that catalyzes this reaction is embedded in the inner membrane of mitochondria, FADH2 transfers its electrons directly to the electron transport chain (ETC).

Question 6: What are the reactions of the tricarboxylic acid cycle?


Acetyl CoA is formed when the end product of glycolysis, pyruvate, condenses with 4 carbon oxaloacetate, which is produced in the Krebs cycle or TCA cycle.

Question 7: What is the significance of the tricarboxylic acid cycle?


Although the ATP generated directly in one TCA cycle is very small (2 molecules of ATP per cycle), it indirectly contributes to the release of many ATP molecules via NADH and FADH2 produced in the cycle.

Both of these are electron carriers that deposit electrons into the electron transport chain (ETC) to drive ATP synthesis via oxidative phosphorylation.

Question 8: Why tricarboxylic acid Cycle classified as an amphibolic pathway? 


An amphibolic pathway is one that functions as both a catabolic and an anabolic pathways. The reaction of Coenzyme A with citrate is anabolic in the TCA cycle, and subsequent steps follow the catabolic pathway. As a result, the TCA cycle is referred to as an Amphibolic pathway.

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