Krebs Cycle Or Citric Acid Cycle: Biochemistry, Metabolism, Enzymes

Edited By Irshad Anwar | Updated on Jul 02, 2025 06:59 PM IST

What Is The Krebs Cycle?

The Krebs cycle, also identified with the terms citric acid cycle and tricarboxylic acid (TCA) cycle, is this important fundamental metabolic pathway that carries much significance in cellular respiration. After glycolysis, the second step regarding aerobic respiration is the Krebs cycle. The cycle takes place in the mitochondrial matrix of all eukaryotic cells. So this is the cycle that converts carbohydrates, fats, and proteins into carbon dioxide, water, and energy.

Krebs Cycle As A Stage Of Cellular Respiration

The most specified stage of cellular respiration is the Krebs cycle, and in such a cycle, all the specified potential chemical energy in glucose and other organics is converted to adenosine triphosphate. As a rule, cellular respiration occurs in three emphasized stages:

Glycolysis: This is a process in which glucose is broken into two pyruvates to give a small product of AT1 and NADH.
Krebs Cycle: Pyruvate gets decarboxylated and enters the mitochondria and thus is oxidized in the Krebs cycle. The result of this oxidation reaction is three molecules, including NADH, FADH2, and GTP/ATP.
Electron Transport Chain and Oxidative Phosphorylation: This energy from NADH and FADH2 provides a series of oxidation-reduction reactions that follow the removal of the protons and electrons; the protons and high-energy electrons extracted in this process are used to pump the electrons in the electron transport chain generating a transmembrane electrochemical gradient, which powers some of the energy thus released.
Citrate is formed by the condensation reaction of acetyl-CoA with oxaloacetate. Citrate is converted to the isomer, isocitrate. Isocitrate reacts with NAD+ to form α-ketoglutarate and NADH. At the same time, a carboxyl group becomes decarboxylated in the oxidative decarboxylation reaction. α-Ketoglutarate reacts with NAD+ forming NADH and succinyl-CoA. Succinyl-CoA reacts with GDP and inorganic phosphate to form succinate and GTP. GTP is used by the cell to make.
Hydratation: Fumarate is hydrated to malate.
Final Oxidation: Malate is oxidised to oxaloacetate producing another NADH.

Overall Summary Of Kreb's Cycle

Krebs cycle can, therefore be summarised as:

Acetyl-CoA joins the cycle through combing with oxaloacetate. Then, citrate is formed.
The cycle follows our line of oxidation and decarboxylation.
It produces NADH and FADH2, where NADH and FADH2 are utilized in the ATP synthesis in the electron transport chain.
It generates carbon dioxide as an excretory product.
Towards the end of the cycle, oxaloacetate is regenerated, and it reloads the same cycle once again.

Krebs Cycle Equation

The overall Krebs cycle can be appropriately represented in the following equation:

Importance Of Krebs Cycle

Energy Production: The most important point regarding the significance of the Krebs cycle, is the line of production for the high-energy electron carriers NADH and FADH2, which, in turn, produce ATP through the electron transport chain.
Carbon Dioxide Production: The cycle is a producer of carbon dioxide, forming a waste product that can be excreted from the body after respiration.
Biosynthesis: Various intermediates of the Krebs cycle serve as a source or precursor of the synthesis of important biomolecules like amino acids and nucleotides.

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Regulation Of The Krebs Cycle

Tightly regulated, the Krebs cycle ensures that the production of energy is accessible in amounts required for metabolic needs. Easily identified control enzymes of the cycle include:

Citrate Synthase: Controls entry of acetyl-CoA into the cycle.
Isocitrate Dehydrogenase: The activity of this enzyme, for the conversion of isocitrate to alpha-ketoglutarate, is controlled by levels of NADH and ATP.
Alpha-Ketoglutarate Dehydrogenase: Logic identical to that of isocitrate dehydrogenase, for a proper balance of energy production about the availability of the substrate.

Relationship Between Glycolysis And The Krebs Cycle

The Krebs cycle is directly connected to glycolysis through pyruvate transformation into acetyl-CoA. After the reception of the end product of glycolysis within the cytoplasm, pyruvate diffused in the mitochondria undergoes oxidative decarboxylation, forming acetyl-CoA and NADH. The acetyl-CoA formed is assimilated into the Krebs cycle and is completely oxidized with the release of energy.

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Frequently Asked Questions (FAQs)

1. What is the major role or function of the Krebs cycle?

Its main function is: the oxidation of acetyl-CoA with the production of carbon dioxide, NADH, and FADH2 required for ATP synthesis in the electron transport chain.

2. Where does the Krebs cycle take place?

The Krebs cycle takes place in the mitochondrial matrix of eukaryotic cells.

3. How many ATP molecules does one turn of the Krebs cycle directly produce?

Through substrate-level phosphorylation, the net gain of one turn of the Krebs cycle directly produces one GTP or ATP.

4. What happens to the carbon dioxide created in the Krebs cycle?

The carbon dioxide that is formed in the Krebs cycle is eliminated from the cell and respired out by the organism.

5. In what manner is the Krebs cycle regulated?

Some key enzymes of the Krebs cycle are under the control of the substrates and products that tend to inhibit to make sure they function at the desired two steps forward and three steps backward manner according to the energy demand of the cell.

6. What is the Krebs cycle and why is it important?

The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a series of chemical reactions in cellular respiration that generates energy from the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. It's important because it produces NADH and FADH2, which are used in the electron transport chain to generate ATP, the cell's energy currency. The cycle also provides precursors for various biosynthetic pathways.

7. What is the role of NAD+ and FAD in the Krebs cycle?

NAD+ and FAD serve as electron acceptors in the Krebs cycle. They are reduced to NADH and FADH2, respectively, by accepting electrons and protons from substrates. These reduced coenzymes then carry the electrons to the electron transport chain, where they are used to generate ATP through oxidative phosphorylation.

8. How does the Krebs cycle contribute to ATP production?

The Krebs cycle contributes to ATP production in two ways:

9. What is the role of α-ketoglutarate dehydrogenase in the Krebs cycle?

α-Ketoglutarate dehydrogenase catalyzes the oxidative decarboxylation of α-ketoglutarate to succinyl-CoA, producing NADH and CO2. This step is important because it's one of the three irreversible reactions in the cycle and is a key regulatory point. The enzyme is inhibited by its products (NADH and succinyl-CoA) and activated by ADP and calcium.

10. How does the Krebs cycle contribute to gluconeogenesis?

The Krebs cycle contributes to gluconeogenesis by providing oxaloacetate, which can be converted to phosphoenolpyruvate, a key intermediate in gluconeogenesis. This process, known as the "malate-aspartate shuttle," allows the transfer of reducing equivalents from the mitochondria to the cytosol, supporting gluconeogenesis.

11. What is the role of succinate dehydrogenase in the Krebs cycle and electron transport chain?

Succinate dehydrogenase is unique because it participates in both the Krebs cycle and the electron transport chain:

12. How does the Krebs cycle contribute to the production of reactive oxygen species?

The Krebs cycle can contribute to the production of reactive oxygen species (ROS) in several ways:

13. What is the importance of the Krebs cycle in plant respiration?

The Krebs cycle is crucial in plant respiration because:

14. How many carbon atoms enter and exit the Krebs cycle?

Two carbon atoms enter the Krebs cycle as part of acetyl-CoA, and two carbon atoms exit the cycle as CO2. This maintains the balance of carbon atoms in the cycle, allowing it to continue indefinitely.

15. What are the main products of the Krebs cycle?

The main products of the Krebs cycle are:

16. How does citrate synthase catalyze the first step of the Krebs cycle?

Citrate synthase catalyzes the condensation of acetyl-CoA with oxaloacetate to form citrate. This reaction is essentially irreversible under physiological conditions and is a major point of regulation for the cycle. The enzyme operates through an ordered sequential mechanism, where oxaloacetate binds first, followed by acetyl-CoA.

17. What is the role of malate dehydrogenase in the Krebs cycle?

Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, using NAD+ as an electron acceptor. This step is important because:

18. What is the significance of fumarase in the Krebs cycle?

Fumarase catalyzes the reversible hydration of fumarate to malate. This enzyme is significant because:

19. Why is the Krebs cycle considered a cyclic process?

The Krebs cycle is considered cyclic because the final product of the cycle, oxaloacetate, is also the starting point. This means that the cycle can continue indefinitely as long as acetyl-CoA is available to combine with oxaloacetate, forming citrate and starting the cycle anew.

20. What is the role of substrate-level phosphorylation in the Krebs cycle?

Substrate-level phosphorylation in the Krebs cycle occurs during the conversion of succinyl-CoA to succinate, catalyzed by succinyl-CoA synthetase. This reaction produces GTP (or ATP in some organisms), which is the only direct ATP equivalent generated in the cycle. While this represents a small portion of the total energy yield, it's significant because it occurs independently of the electron transport chain.

21. How does the Krebs cycle interact with the electron transport chain?

The Krebs cycle interacts with the electron transport chain by:

22. How does the Krebs cycle contribute to the cell's redox balance?

The Krebs cycle plays a crucial role in maintaining the cell's redox balance by:

23. What is the importance of aconitase in the Krebs cycle?

Aconitase catalyzes the reversible isomerization of citrate to isocitrate via cis-aconitate. This enzyme is important because:

24. What is the significance of isocitrate dehydrogenase in the Krebs cycle?

Isocitrate dehydrogenase is a key regulatory enzyme in the Krebs cycle. It catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, producing NADH and CO2. This step is important because it's one of the rate-limiting steps of the cycle and is allosterically regulated by ATP, NADH, and ADP.

25. How does oxygen availability affect the Krebs cycle?

Oxygen is not directly involved in the Krebs cycle reactions. However, oxygen availability indirectly affects the cycle by influencing the electron transport chain. Without oxygen as the final electron acceptor, the electron transport chain slows down, leading to an accumulation of NADH. This high NADH/NAD+ ratio inhibits several enzymes in the Krebs cycle, slowing it down.

26. How is the Krebs cycle regulated?

The Krebs cycle is regulated through several mechanisms:

27. What is the role of succinyl-CoA synthetase in the Krebs cycle?

Succinyl-CoA synthetase catalyzes the conversion of succinyl-CoA to succinate, coupled with the production of GTP (or ATP in some organisms). This step is important because it's the only step in the Krebs cycle that directly produces a high-energy phosphate compound through substrate-level phosphorylation.

28. What is the connection between the Krebs cycle and amino acid metabolism?

The Krebs cycle is connected to amino acid metabolism in several ways:

29. How does the Krebs cycle connect to glycolysis?

The Krebs cycle connects to glycolysis through the conversion of pyruvate to acetyl-CoA. Glycolysis produces pyruvate in the cytoplasm, which then enters the mitochondria and is converted to acetyl-CoA by the pyruvate dehydrogenase complex. This acetyl-CoA then enters the Krebs cycle.

30. How does the Krebs cycle relate to fatty acid metabolism?

The Krebs cycle is closely linked to fatty acid metabolism through acetyl-CoA. When fatty acids are broken down through β-oxidation, they produce acetyl-CoA, which can then enter the Krebs cycle. This allows cells to generate energy from fat stores when glucose is not readily available.

31. Where does the Krebs cycle occur in plant cells?

In plant cells, the Krebs cycle occurs in the matrix of mitochondria. Mitochondria are often called the "powerhouses" of the cell because they generate most of the cell's supply of ATP through the processes of the Krebs cycle and electron transport chain.

32. What is anaplerosis in the context of the Krebs cycle?

Anaplerosis refers to the replenishment of intermediates in the Krebs cycle. As cycle intermediates are used for biosynthetic processes, they need to be replaced to keep the cycle running. Anaplerotic reactions, such as the conversion of pyruvate to oxaloacetate by pyruvate carboxylase, help maintain the cycle's function by replenishing these intermediates.

33. How does the Krebs cycle differ between plants and animals?

The Krebs cycle is fundamentally similar in plants and animals, but there are some differences:

34. What is the significance of the glyoxylate cycle in plants, and how does it relate to the Krebs cycle?

The glyoxylate cycle is a variation of the Krebs cycle found in plants, bacteria, and some fungi. It allows these organisms to convert acetyl-CoA from fatty acid breakdown into glucose. The glyoxylate cycle shares some enzymes with the Krebs cycle but bypasses the CO2-generating steps, allowing for net carbon gain. This is particularly important for seed germination in plants, where stored fats are converted to carbohydrates.

35. How does the Krebs cycle contribute to biosynthetic pathways?

The Krebs cycle contributes to biosynthetic pathways by providing precursor molecules:

36. How does the Krebs cycle adapt to different energy states in the cell?

The Krebs cycle adapts to different energy states through several mechanisms:

37. How does the Krebs cycle relate to photorespiration in plants?

The Krebs cycle interacts with photorespiration in several ways:

38. What is the role of pyruvate dehydrogenase in relation to the Krebs cycle?

Pyruvate dehydrogenase, while not part of the Krebs cycle itself, plays a crucial role in linking glycolysis to the cycle:

39. How does the Krebs cycle contribute to nitrogen assimilation in plants?

The Krebs cycle contributes to nitrogen assimilation in plants by:

40. What is the significance of isocitrate lyase in some plants and microorganisms?

Isocitrate lyase is an enzyme of the glyoxylate cycle, found in some plants (especially in seeds) and microorganisms: