Link Reaction Between Glycolysis And Krebs Cycle: Diagrams, Equation & Steps

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

What Is Glycolysis And Kreb Cycle?

Glycolysis and the Krebs cycle are two dependent ways in cellular metabolic processes, relevant to cell respiration. The two processes are above all pathways in which the conversion of glucose occurs to generate usable energy in the form of ATP. Besides, glycolysis occurs in the cytoplasm, and the Krebs cycle occurs in the mitochondria. Elucidating how these two pathways relate to one another is key to understanding how it is that cells generate energy.

Overview Of Glycolysis

Glycolysis is a metabolic pathway that oxidizes glucose, a six-carbon sugar, into two molecules of pyruvate, a three-carbon compound, in the presence of an inorganic phosphate, a coenzyme of the B_vitamin niacin. In addition, this ten-step process takes place in the cytoplasm since it does not involve any oxygen molecules; hence, it is considered anaerobic. Glycolysis includes ten enzymatic reactions that eventually convert glucose into pyruvate and build a net gain of two ATP and two NADH molecules.

Steps

Energy Investment Phase:

This is where two molecules of ATP get used up in phosphorylating glucose and its derivatives to get them ready for a complete breakdown.

Energy Payoff Phase:

In this phase, four ATP molecules are produced when the glucose is converted into two molecules of pyruvate. In the overall accounting, the net gain from glycolysis is two ATP molecules because two were used in the investment phase.

Fate Of Pyruvate

After glycolysis has occurred, the direction that the pyruvate takes is determined by the conditions to which it is exposed:

Aerobic Conditions:

In the presence of oxygen, the pyruvate diffuses into the mitochondria where it is then oxidatively decarboxylated to acetyl-CoA. This process is catalyzed by the pyruvate dehydrogenase complex. Concomitantly, the coenzyme NAD+ to NADH is reduced and carbon dioxide is released.

Anaerobic Conditions:

In the absence of oxygen, the pyruvate is often converted to either lactic acid by fermentation in animal muscles or to ethanol and carbon dioxide in yeast fermentation processes.

The Krebs Cycle

The Krebs cycle involves a series of enzymatic reactions in the mitochondrial matrix, in which the reaction starts with condensation of acetyl-CoA with oxaloacetate into citrate. It involves several oxidations And decarboxylations of the compounds, which in the end lead to the reformation of oxaloacetate to start the cycle all over again.

Krebs Cycle Steps

The Krebs cycle can be summarized in the following steps:

Formation of Citrate: Acetyl-CoA combines with the oxaloacetate to produce citrate.
Isomerisation: Migration of the citrate mould to give isocitrate
Oxidative Decarboxylation: Loss of carbon from isocitrate to give alpha-ketoglutarate, with the generation of NADH (and carbon dioxide)
Further Decarboxylation: Conversion of alpha-ketoglutarate to succinyl-CoA, with the generation of another NADH (and carbon dioxide)
Substrate-level phosphorylation: Conversion of succinyl-CoA to succinate, with the creation of GTP (or ATP)

Linking Glycolysis And The Krebs Cycle

The link between glycolysis and the Krebs cycle is established through pyruvate-to-acetyl-CoA conversion. Therefore, this reaction links the two pathways, now allowing the products from glycolysis to move into the Krebs cycle for further energy extraction.

Glycolysis Produces Pyruvate: It converts glucose into pyruvate, which is the key intermediate linking the two pathways.
Conversion to Acetyl-CoA: In an aerobic environment, pyruvate first converts into acetyl-CoA that is located within the mitochondria and eventually goes into the Krebs cycle.
Energy Production: The responsibility of the Krebs cycle is that it will take the figure of acetyl-CoA to generate both NADH and FADH2 that are needed for the electron transport chain and ATP synthesis, respectively.

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Regulation Of The Pathways

To maintain homeostasis in cell energy, both the glycolytic pathway and the Krebs cycle are highly regulated. The key regulation of these two pathways is shown below:

Hexokinase and phosphofructokinase during glycolysis, are influenced by ATP, ADP, and other metabolites; II.
Pyruvate dehydrogenase linking glycolysis to the Krebs cycle, controlled by the availability of substrates and products; III.
Isocitrate dehydrogenase and α-ketoglutarate dehydrogenases in the Krebs cycle, which respond to energy levels within the cell.

Glycolysis And Krebs Cycle: Their Significance

The role of both glycolysis and the Krebs cycle in cellular respiration is one of collaboration. The pathways, aside from their ATP generation, also provide intermediates for many biosynthetic pathways. Any failures in these pathways will surely lead to disturbances in metabolic activity and hence affect overall cell function.

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Frequently Asked Questions (FAQs)

1. What is glycolysis?

Glycolysis is the process of metabolizing glucose to pyruvate with a net profit of two ATP molecules and two NADH molecules.

2. Where does the Krebs cycle occur?

The Krebs cycle occurs in the mitochondrial matrix of eukaryotic cells.

3. What is the fate of pyruvate under aerobic conditions?

Pyruvate is converted to acetyl-CoA under aerobic conditions. Acetyl-CoA then goes to the Krebs cycle.

4. How do glycolysis and Krebs cycle produce ATP?

Through glycolysis some ATP molecules are produced directly while from the Krebs cycle, NADH and FADH2 donate electrons to electron transport to make more ATP.

5. What are the ways of regulating of the glycolytic pathway and the Krebs cycle?

The availability of substrates, products, and energy levels of the cell control a key enzyme for both pathways, in a cellular environment wherein the efficient production of energy occurs.

6. How many molecules of acetyl-CoA are produced from one glucose molecule during glycolysis and the link reaction?

One glucose molecule produces two pyruvate molecules during glycolysis. Each pyruvate then undergoes the link reaction to form one acetyl-CoA. Therefore, one glucose molecule ultimately yields two acetyl-CoA molecules.

7. What cofactors are required for the pyruvate dehydrogenase complex to function?

The pyruvate dehydrogenase complex requires several cofactors to function properly, including:

8. How does the link reaction contribute to the overall oxidation state of glucose during cellular respiration?

The link reaction significantly contributes to increasing the oxidation state of glucose during cellular respiration. In glycolysis, glucose (oxidation state 0) is partially oxidized to pyruvate (higher oxidation state). The link reaction further oxidizes pyruvate by removing electrons (forming NADH) and a carbon atom (as CO2), producing acetyl-CoA. This prepares the remaining carbon atoms for complete oxidation in the Krebs cycle, representing a crucial step in the stepwise oxidation of glucose to CO2 and H2O.

9. In which cellular compartment does the link reaction occur?

The link reaction occurs in the mitochondrial matrix, the innermost compartment of the mitochondrion. This is where pyruvate from glycolysis is transported to undergo the transition to acetyl-CoA.

10. What is the relationship between the link reaction and gluconeogenesis?

The link reaction and gluconeogenesis have an inverse relationship. While the link reaction converts pyruvate to acetyl-CoA, committing it to energy production, gluconeogenesis needs to generate glucose from pyruvate. Since the link reaction is irreversible, gluconeogenesis must bypass it using different enzymes. Specifically, pyruvate carboxylase converts pyruvate to oxaloacetate, which can then be used to produce phosphoenolpyruvate, effectively reversing part of glycolysis.

11. What happens if the link reaction is impaired or blocked?

If the link reaction is impaired or blocked, pyruvate cannot be converted to acetyl-CoA efficiently. This leads to a buildup of pyruvate and a shortage of acetyl-CoA. As a result, the Krebs cycle cannot proceed normally, leading to reduced ATP production through oxidative phosphorylation. In severe cases, this can lead to lactic acid buildup and metabolic acidosis.

12. What would happen to cellular energy production if the link reaction was completely blocked?

If the link reaction was completely blocked, it would severely impair cellular energy production. Glycolysis could still occur, producing a small amount of ATP, but the majority of ATP production from glucose oxidation would be lost. The Krebs cycle and electron transport chain would lack the acetyl-CoA fuel and NADH electron carriers normally provided by the link reaction, leading to a significant energy deficit in the cell.

13. How does the link reaction contribute to the oxidation state of the carbon atoms from glucose?

The link reaction further oxidizes the carbon atoms from glucose. In glycolysis, glucose (with an oxidation state of 0) is oxidized to pyruvate (with a higher oxidation state). The link reaction continues this oxidation process by removing more electrons and a carbon atom, forming acetyl-CoA. This prepares the remaining carbon atoms for complete oxidation in the Krebs cycle.

14. What is the fate of the CO2 produced during the link reaction?

The CO2 produced during the link reaction diffuses out of the mitochondria and eventually out of the cell. It can then be used in other metabolic processes (like photosynthesis in plants) or expelled from the organism through respiration.

15. How does the link reaction contribute to the energy yield of cellular respiration?

While the link reaction itself doesn't produce ATP directly, it generates NADH, which carries high-energy electrons to the electron transport chain. These electrons are ultimately used to produce ATP through oxidative phosphorylation. Additionally, by producing acetyl-CoA, it provides the starting material for the Krebs cycle, which generates more reduced electron carriers.

16. How does the link reaction contribute to the production of citric acid in the Krebs cycle?

The link reaction produces acetyl-CoA, which is the crucial two-carbon compound that enters the Krebs cycle. In the first step of the Krebs cycle, acetyl-CoA combines with oxaloacetate (a four-carbon compound) to form citric acid (a six-carbon compound). Without the acetyl-CoA produced by the link reaction, the Krebs cycle could not begin.

17. What is the overall equation for the link reaction?

The overall equation for the link reaction is:

18. What is the role of coenzyme A in the link reaction?

Coenzyme A (CoA) plays a crucial role in the link reaction by accepting the acetyl group from pyruvate. It forms acetyl-CoA, which is the end product of the link reaction and the starting substrate for the Krebs cycle. CoA acts as a carrier molecule, transferring the acetyl group into the Krebs cycle.

19. How does the link reaction differ from substrate-level phosphorylation?

The link reaction differs from substrate-level phosphorylation in that it does not directly produce ATP. Instead, it generates NADH and acetyl-CoA. Substrate-level phosphorylation, which occurs in glycolysis and the Krebs cycle, involves the direct transfer of a phosphate group from a substrate to ADP, forming ATP. The link reaction prepares substrates for further oxidation and indirectly contributes to ATP production through NADH.

20. How does the link reaction relate to the concept of carbon flux in metabolism?

The link reaction is a critical point in carbon flux through central metabolism. It represents the junction where carbon from various sources (carbohydrates, some amino acids) is channeled into the Krebs cycle as acetyl-CoA. The rate of the link reaction can thus influence the overall flux of carbon through central energy-producing pathways, affecting the balance between catabolism (breaking down molecules for energy) and anabolism (building up molecules for cellular structures and functions).

21. What is the link reaction in cellular respiration?

The link reaction, also known as the transition reaction or pyruvate oxidation, is the process that connects glycolysis to the Krebs cycle. It occurs in the mitochondrial matrix and converts pyruvate from glycolysis into acetyl-CoA, which then enters the Krebs cycle.

22. Why is the link reaction considered a "bridge" between glycolysis and the Krebs cycle?

The link reaction is considered a bridge because it connects two major metabolic pathways: glycolysis, which occurs in the cytoplasm, and the Krebs cycle, which takes place in the mitochondrial matrix. It transforms the end product of glycolysis (pyruvate) into a form (acetyl-CoA) that can enter and fuel the Krebs cycle.

23. What is the main enzyme involved in the link reaction?

The main enzyme involved in the link reaction is the pyruvate dehydrogenase complex (PDC). This large, multi-enzyme complex catalyzes the oxidative decarboxylation of pyruvate to form acetyl-CoA.

24. How many carbon atoms are in pyruvate, and how many are in acetyl-CoA?

Pyruvate has three carbon atoms, while acetyl-CoA has two carbon atoms. During the link reaction, one carbon atom is lost as CO2, which is why this process is called oxidative decarboxylation.

25. What happens to the hydrogen atoms removed from pyruvate during the link reaction?

The hydrogen atoms removed from pyruvate are transferred to NAD+ to form NADH. This reduction of NAD+ to NADH is an important step in the overall process of cellular respiration, as NADH carries electrons to the electron transport chain for ATP production.

26. How does the link reaction differ in anaerobic conditions?

The link reaction typically doesn't occur under anaerobic conditions. Without oxygen, cells rely more heavily on glycolysis for energy production. In many organisms, pyruvate is instead converted to lactate (in animals) or ethanol (in yeast) through fermentation. These processes regenerate NAD+ to keep glycolysis running but do not produce acetyl-CoA or feed into the Krebs cycle.

27. What is the role of the link reaction in the Cori cycle?

The link reaction is indirectly involved in the Cori cycle. In this cycle, lactate produced by anaerobic glycolysis in muscles is transported to the liver, where it's converted back to pyruvate. This pyruvate can then enter the link reaction to produce acetyl-CoA for energy production in the liver. Alternatively, it can be used for gluconeogenesis, producing glucose that is then sent back to the muscles, completing the cycle.

28. How is the link reaction regulated in cells?

The link reaction is primarily regulated through the activity of the pyruvate dehydrogenase complex (PDC). PDC is inhibited by high levels of acetyl-CoA and NADH, which are its products. It's also inhibited by ATP, indicating sufficient energy in the cell. Conversely, PDC is activated by ADP and NAD+, signaling a need for more energy production.

29. What is the connection between the link reaction and gluconeogenesis?

The link reaction is essentially irreversible under physiological conditions, making it a key regulatory point in metabolism. When gluconeogenesis (the production of glucose from non-carbohydrate precursors) is needed, cells must bypass the link reaction. This is done through alternative pathways that convert pyruvate back to phosphoenolpyruvate, effectively reversing part of glycolysis.

30. What is the significance of the irreversibility of the link reaction?

The irreversibility of the link reaction is significant because it commits the carbon atoms from pyruvate to enter the Krebs cycle and undergo complete oxidation. This irreversibility serves as a key regulatory point in metabolism, ensuring that once glucose has been broken down to pyruvate and entered the mitochondria, it will be fully oxidized for energy production rather than being reconverted to glucose.

31. How does thiamine deficiency affect the link reaction?

Thiamine (vitamin B1) is a precursor to thiamine pyrophosphate (TPP), a crucial cofactor for the pyruvate dehydrogenase complex. Thiamine deficiency can severely impair the link reaction, leading to a buildup of pyruvate and lactic acid. This can result in metabolic acidosis and neurological symptoms, as seen in conditions like beriberi and Wernicke-Korsakoff syndrome.

32. What is the connection between the link reaction and fatty acid oxidation?

Both the link reaction and fatty acid oxidation produce acetyl-CoA, which then enters the Krebs cycle. However, fatty acid oxidation (beta-oxidation) produces acetyl-CoA directly from fatty acids, bypassing the need for the link reaction. The acetyl-CoA from both sources is chemically identical and is processed the same way in the Krebs cycle.

33. How does the structure of the mitochondrion facilitate the link reaction?

The structure of the mitochondrion facilitates the link reaction by providing a specialized compartment (the matrix) where the reaction can occur efficiently. The inner mitochondrial membrane contains specific transporters that bring pyruvate into the matrix. Once inside, pyruvate is in close proximity to the enzymes of the pyruvate dehydrogenase complex and the subsequent Krebs cycle, allowing for efficient metabolic flow.

34. What is the role of biotin in relation to the link reaction and subsequent metabolic steps?

While biotin is not directly involved in the link reaction, it plays a crucial role in a related process. Biotin is a cofactor for pyruvate carboxylase, an enzyme that converts pyruvate to oxaloacetate. This reaction is important for replenishing Krebs cycle intermediates (anaplerosis) and is a key step in gluconeogenesis. The activity of pyruvate carboxylase can influence the fate of pyruvate, potentially directing it away from the link reaction under certain metabolic conditions.

35. How does the link reaction contribute to the production of biosynthetic precursors?

While the primary role of the link reaction is to feed acetyl-CoA into the Krebs cycle for energy production, it also indirectly contributes to biosynthesis. The acetyl-CoA produced can be used as a precursor for fatty acid and cholesterol synthesis. Additionally, the NADH produced can provide reducing power for various biosynthetic reactions. The CO2 released can be used in carboxylation reactions in pathways like gluconeogenesis and fatty acid synthesis.

36. What is the connection between the link reaction and amino acid metabolism?

The link reaction connects to amino acid metabolism in several ways:

37. How does the link reaction contribute to the concept of metabolic flexibility?

The link reaction contributes to metabolic flexibility by serving as a junction point between different metabolic pathways. It allows cells to shift between using carbohydrates and certain amino acids for energy production. The regulation of the pyruvate dehydrogenase complex allows cells to adjust the flow of carbon into the Krebs cycle based on energy needs and the availability of different fuel sources, enhancing the cell's ability to adapt to changing metabolic conditions.

38. What is the evolutionary significance of the link reaction?

The link reaction is evolutionarily significant as it represents a key step in the development of efficient energy production in cells. It allows for the complete oxidation of glucose by connecting glycolysis (an ancient metabolic pathway that can occur without oxygen) to the Krebs cycle and electron transport chain (which require oxygen). This connection enabled organisms to extract much more energy from glucose, supporting the evolution of complex life forms.

39. What is the significance of the link reaction in cancer metabolism?

The link reaction plays a significant role in cancer metabolism. Many cancer cells exhibit the War

40. How does the link reaction differ between prokaryotic and eukaryotic cells?

In prokaryotic cells, which lack mitochondria, the link reaction occurs in the cytoplasm along with other steps of cellular respiration. In eukaryotic cells, the link reaction takes place specifically in the mitochondrial matrix. The basic chemistry and enzymes involved are similar, but the cellular location differs.

41. What is the role of lipoic acid in the link reaction?

Lipoic acid is a cofactor in the pyruvate dehydrogenase complex. It acts as a "swinging arm" that transfers the acetyl group from one part of the enzyme complex to another. Specifically, it accepts the acetyl group from thiamine pyrophosphate and then transfers it to coenzyme A, facilitating the formation of acetyl-CoA.

42. How does the pH of the mitochondrial matrix affect the link reaction?

The pH of the mitochondrial matrix can significantly affect the link reaction. The pyruvate dehydrogenase complex functions optimally at a slightly alkaline pH (around 7.8-8.0), which is maintained in the mitochondrial matrix. If the pH becomes too acidic or too alkaline, it can alter the structure and function of the enzymes involved in the link reaction, potentially slowing or inhibiting the process.

43. What is the relationship between the link reaction and ketone body production?

The link reaction and ketone body production are inversely related. When glucose is scarce and fatty acid oxidation is high (such as during fasting or in diabetes), the rate of the link reaction decreases. Instead, the acetyl-CoA produced from fatty acid oxidation is diverted to ketone body production in the liver. Ketone bodies then serve as an alternative fuel source for tissues like the brain that normally rely heavily on glucose.

44. How does the link reaction relate to the concept of anaplerosis?

The link reaction is indirectly related to anaplerosis, which is the replenishment of Krebs cycle intermediates. While the link reaction provides acetyl-CoA that enters the Krebs cycle, it doesn't increase the amount of cycle intermediates. However, when the link reaction is less active (e.g., during glucose shortage), anaplerotic reactions like the carboxylation of pyruvate to oxaloacetate become more important to maintain Krebs cycle function.