Lesson Explainer: The Link Reaction and Krebs Cycle Biology

In this explainer, we will learn how to describe the steps of the link reaction and the Krebs cycle and recall the products of each.

Cellular respiration is one of the most important biological processes for sustaining life on Earth. Nearly every living organism uses cellular respiration to release energy and uses this energy to fuel movement, digestion, reproduction, and growth.

Definition: Cellular Respiration

Cellular respiration is a process in living organisms through which carbon-containing compounds (such as glucose) are broken down to release energy in the form of ATP.

Cellular respiration refers to the series of reactions that break down “fuel” in the form of glucose, or other respiratory substrates into smaller molecules, releasing energy in the process. This energy is contained in the energy-carrying molecule ATP, which is readily available for cells to use as and when they need it.

Cellular respiration can be divided into four main sequential stages: glycolysis, the link reaction, the Krebs cycle (also referred to as the citric acid cycle), and oxidative phosphorylation (also referred to as the electron transport chain). In this explainer, we will look at the middle two stages in more detail.

Glycolysis occurs in the cytoplasm and will take place whether oxygen is present or not. Both the link reaction and the Krebs cycle occur in the mitochondria of cells. The mitochondria are specialized organelles that act as the site of the aerobic stages of respiration. Aerobic means “with oxygen.” All the subsequent stages of respiration that follow glycolysis are known as aerobic, because they require oxygen to be present to take place.

Example 1: Stating the Cellular Organelle That Is the Site of Aerobic Cellular Respiration

In eukaryotes, what cellular organelle is the site of the link reaction and Krebs cycle?

  1. Smooth endoplasmic reticulum
  2. Ribosome
  3. The mitochondria
  4. Nucleus
  5. Golgi apparatus

Answer

Cellular respiration is the process by which carbon-containing compounds, like glucose, are broken down to release energy. It consists of four main stages: glycolysis, the link reaction, the Krebs cycle, and oxidative phosphorylation.

Let’s remind ourselves of the general structure of a typical eukaryotic cell.

The first stage of cellular respiration is glycolysis, and it takes place in the cytoplasm of cells. This is the jellylike substance that fills the cell and in which all other organelles are suspended.

The products of glycolysis form the reactants of the link reaction. These products are transported from the cytoplasm into the mitochondria. The mitochondria are small cellular organelles that act as the site for all the aerobic stages of cellular respiration. This means that both the link reaction and Krebs cycle, along with oxidative phosphorylation, occur in the mitochondria.

Therefore, the cellular organelle that is the site of the link reaction and Krebs cycle is the mitochondria.

The link reaction refers to the stage of respiration that “links” glycolysis to the Krebs (citric acid) cycle. In this stage, the products of glycolysis are converted into the reactants of the Krebs cycle. A simple outline of the link reaction is given in Figure 1.

Figure 1: An illustration of the link reaction. The number of carbon atoms in each compound is represented by the orange circles.

In the link reaction, the 3-carbon compound pyruvate (or pyruvic acid) is converted into the 2-carbon compound acetyl coenzyme A. In a series of steps, the pyruvate molecule undergoes the following changes:

  1. Pyruvate is oxidized and loses a carbon atom to become a 2-carbon compound.
  2. This carbon atom is released in the form of carbon dioxide.
  3. The 2-carbon compound is oxidized, and it transfers electrons to NAD.
  4. The coenzyme NAD becomes reduced NAD (NADH) as it gains a hydrogen and two electrons.
  5. Coenzyme A attaches to the 2-carbon compound to form acetyl coenzyme A.

Key Term: Acetyl Coenzyme A (Acetyl-CoA)

Acetyl coenzyme A is a 2-carbon compound formed from the oxidization of pyruvate and the attachment of coenzyme A. It is a product of the link reaction and a reactant of the Krebs (citric acid) cycle.

Example 2: Recalling the Reactants and Products of the Link Reaction

The diagram provided shows a basic outline of the link reaction, with the names of two compounds removed.

  1. What compound has been replaced by the letter Y?
    1. Coenzyme A
    2. Triose phosphate
    3. Acetyl-CoA
    4. ATP
  2. What compound has been replaced by the letter X?
    1. Triose phosphate
    2. Acetyl-CoA
    3. Coenzyme A
    4. ATP

Answer

The link reaction refers to a stage in cellular respiration that “links” two other stages. The link reaction takes the products of the first stage, glycolysis, and converts them into reactants that will enter the Krebs cycle.

The primary product of glycolysis is the 3-carbon compound pyruvate. To convert this into a reactant of the Krebs cycle, a series of reactions take place.

Firstly, a carbon dioxide molecule is removed from pyruvate. This converts the 3-carbon compound into a 2-carbon one. Then, the compound is oxidized, and it transfers a hydrogen to the coenzyme NAD to form NADH. Finally, coenzyme A attaches to this 2-carbon compound to form acetyl coenzyme A. Acetyl coenzyme A then enters the Krebs cycle.

Part 1

If we look back at our diagram, “Y” indicates a compound that reacts with a two-carbon molecule to convert it into compound “X.” If we revisit our description of the link reaction, we can see that after a carbon is removed in the form of carbon dioxide, coenzyme A attaches to the two-carbon compound.

Therefore, “Y” must be “coenzyme A.”

Part 2

In the diagram in the question, “X” indicates the final product of the link reaction. Looking back at our description of the link reaction, we know the overall aim of the link reaction is to convert pyruvate into acetyl coenzyme A. Acetyl coenzyme A, or acetyl-CoA for short, is the primary reactant of the next stage of cellular respiration, the Krebs cycle.

Therefore “X” must be “acetyl-CoA.”

Acetyl coenzyme A, the final product of the link reaction, now enters the Krebs cycle. A basic outline of the Krebs cycle is given in Figure 2 below.

Figure 2: A basic outline of the Krebs cycle, also referred to as the citric acid cycle. The number of carbons in each compound is indicated by the orange circles.

When acetyl coenzyme A enters the Krebs cycle, it binds to a 4-carbon compound, oxaloacetic acid (or oxaloacetate). This forms a 6-carbon compound known as citric acid (or citrate). This compound gives the Krebs cycle its alternative name of the citric acid cycle.

Citric acid then passes through a series of reactions, forming intermediate compounds.

Firstly, citric acid loses a carbon in the form of carbon dioxide to form a 5-carbon compound. It is also oxidized, and it transfers a hydrogen (along with two electrons) to NAD that forms reduced NAD, or NADH. The resulting compound is called ketoglutaric acid (or ketoglutarate).

From this intermediate 5-carbon compound, ketoglutaric acid, another carbon atom is lost as carbon dioxide, and another NAD is reduced by accepting a hydrogen atom. Alongside this, a molecule of ADP is phosphorylated to produce a molecule of ATP. This series of reactions forms an intermediate 4-carbon compound called succinic acid (or succinate).

Key Term: ATP (Adenosine Triphosphate)

ATP, or adenosine triphosphate, is the molecule that stores chemical energy in living organisms.

Succinic acid now undergoes a series of reactions to regenerate our previously mentioned 4-carbon compound, oxaloacetic acid. Succinic acid is oxidized firstly as it transfers two hydrogens to FAD to form reduced FAD ()FADH and again as it transfers another hydrogen and two electrons to NAD to form reduced NAD.

Now, we have completed a full cycle! The regenerated oxaloacetic acid is now ready to join another molecule of acetyl coenzyme A and start the cycle again.

Example 3: Identifying the Reactants and Products of the Krebs Cycle

The diagram provided shows a basic outline of the Krebs cycle.

  1. What reactant has been replaced by the letter X?
    1. Carbon dioxide
    2. Coenzyme A
    3. NAD
    4. Reduced NAD
  2. What product has been replaced by the letter Y?
    1. NAD
    2. Reduced NAD
    3. Carbon dioxide
    4. Coenzyme A

Answer

The Krebs cycle—also known as the citric acid cycle—refers to an important stage in cellular respiration. In the Krebs cycle, acetyl coenzyme A produced by the link reaction joins the 4-carbon compound oxaloacetic acid (or oxaloacetate) to form the 6-carbon compound citric acid (or citrate).

Then, in a series of reactions, oxaloacetic acid is regenerated from citric acid. In these reactions, other products are formed and released from the Krebs cycle. These products include two molecules of carbon dioxide (CO)2 and one molecule of ATP, as shown in the diagram.

As well as these molecules, there are coenzymes, NAD and FAD, that are reduced in the cycle. Reduction is a word used to describe reactions where a molecule gains electrons. We can see in the diagram of the Krebs cycle that FAD is converted into reduced FAD (or FADH). However, NAD and reduced NAD are missing from the cycle.

Part 1

The letter X indicates a missing reactant that enters the Krebs cycle and produces product Y. Looking at the diagram and the explanation provided, we can see that the missing reactant from the cycle that has been replaced by the letter X is the coenzyme NAD.

Part 2

The letter Y indicates a product that has been generated from reactant X. Looking at the diagram and the explanation provided, we can see that the missing product from the cycle that has been replaced by the letter Y is reduced NAD.

As we have come full circle, you may be wondering, what is the point of the Krebs cycle? To answer this question, let’s summarize the products of the Krebs cycle.

In Figure 3, we have removed the intermediate compounds from the Krebs cycle to see the products better.

Figure 3: Reactants and products of the Krebs cycle, with the intermediate compounds removed.

It is important to remember that for each molecule of glucose, two molecules of pyruvate are produced, which means they are converted into two molecules of acetyl coenzyme A. This means for one molecule of glucose, the Krebs cycle happens twice. So, we need to double the products we see in Figure 3.

Therefore, for each molecule of glucose that enters respiration, the Krebs cycle produces

  • four molecules of carbon dioxide,
  • six molecules of reduced NAD (NADH),
  • two molecules of reduced FAD ()FADH,
  • two molecules of ATP.

Example 4: Recalling How Many ATP Molecules Are Produced per Turn of the Krebs Cycle

For each turn of the Krebs cycle, how many molecules of ATP are produced?

Answer

The Krebs cycle is a crucial stage in the series of biochemical reactions that make up cellular respiration. The overall aim of cellular respiration is to break down carbon-containing compounds to release energy that can be used by cells to carry out essential life-maintaining functions.

The energy released in these reactions cannot always be used immediately. In this case, ATP acts as an energy-carrying molecule as it can be easily transported around the cell and broken down to release manageable amounts of energy.

The main reactant of the Krebs cycle is a molecule of acetyl coenzyme A, which is produced by the preceding link reaction. This joins with a 4-carbon compound called oxaloacetic acid (or oxaloacetate) to form a 6-carbon compound called citric acid (or citrate). Citric acid then undergoes a series of reactions to regenerate oxaloacetic acid.

One of these reactions converts a 5-carbon compound into a 4-carbon compound. Alongside the loss of a carbon atom in the form of carbon dioxide and a hydrogen atom to NAD, this reaction is coupled (joined) to the phosphorylation of an ADP molecule. When ADP (adenosine diphosphate) is phosphorylated, it gains a phosphate group and forms ATP (adenosine triphosphate).

This phosphorylation of ADP only occurs in one reaction from the series that make up the Krebs cycle.

So, for one turn of the Krebs cycle, one molecule of ATP is produced.

We know that ATP is a very useful molecule to have in cells; ATP can be easily transported around the cell and hydrolyzed relatively easily to release energy quickly. The molecules of carbon dioxide are the waste products of cellular respiration, and these will diffuse out of the mitochondria and the cell and eventually will be excreted from the body in sweat or via the lungs.

In the Krebs cycle, FAD and NAD act as electron acceptors and form FADH and NADH. FADH and NADH are crucial for the next, and final, stage of aerobic cellular respiration, which is oxidative phosphorylation. They will transfer the electrons they have accepted at this stage to the electron transport chain.

Let’s summarize what we have learnt about the link reaction and the Krebs cycle.

Key Points

  • The link reaction converts pyruvate produced by glycolysis into acetyl coenzyme A, which enters the Krebs cycle.
  • Acetyl coenzyme A joins oxaloacetic acid to form citric acid.
  • Citric acid undergoes a series of reactions to reform oxaloacetic acid.
  • In this process, two molecules of carbon dioxide and one molecule of ATP are released.
  • FAD and NAD act as electron acceptors in the Krebs cycle and form reduced FAD and reduced NAD.

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