The Krebs Cycle | A Step-by-Step Explanation

Last Updated on March 5, 2024 by Nourhan Essam

You’ve probably heard the phrase Krebs cycle thrown around before. If you’re at all interested in biology, general science, etc. Then you know that the Krebs cycle has a vital role inside our bodies. But what exactly is it? Why does it deserve such an important name? You know what I’m talking about — The Krebs Cycle.

The Krebs cycle is a series of chemical reactions that help break down and release energy stored in food. The Krebs cycle is also known as the tricarboxylic acid (TCA) cycle or the citric acid cycle. The Krebs cycle is often considered to be the central hub of cellular metabolism, performing many important biochemical reactions that ultimately produce ATP.

This article takes a closer look at the Krebs cycle steps, how it works, what is the purpose of it, its diagram, also where does Krebs cycle occur, its products and more. Read our article and get all your questions answered with step by step explanations.

What Is the Krebs Cycle?

The Krebs cycle definition is a sequence of chemical reactions that occur in the body. The cycle starts with the intake of food, which is broken down into small molecules by the stomach and intestines. These molecules are then absorbed by the body through the small intestines and transported to the liver via the bloodstream. In the liver, the molecules are broken down further into smaller pieces called amino acids.

In the next step of the cycle, these amino acids are converted into glucose through a series of chemical reactions called phosphorylation. Then, the glucose enters the main cells of the body and can be used for energy or can be stored as glycogen for later use. When the body needs more energy, it stores the excess glucose as glycogen.

Glycogen is a form of starch stored in the liver and muscles that is used by the body for energy during periods of fasting or when no food is eaten for an extended period of time. If the body has excess energy after using up its supply of glycogen, it can then break down the remaining stored fat into fatty acids.

Where Does the Krebs Cycle Take Place?

The Krebs cycle takes place exactly in (the mitochondrial matrix) and converts mitochondrial pyruvate into carbon dioxide and water. The mitochondrial matrix is a dense solution that surrounds the crests of the mitochondria. This matrix contains water, all the needed enzymes, coenzymes, and phosphates which are necessary for the Krebs cycle reactions.

The Main Purpose of Krebs Cycle

Briefly the purpose of the Krebs cycle is to combine carbon dioxide and water using energy from the electron transport chain. The resulting molecules are then used for the purposes of generating energy and building cells.

We can also say that the purpose of the Krebs cycle is to help cells convert glucose into energy and provide ATP, which is one unit of energy. The beginning of the end-products are very high energy and end up being used as ATP in your cells.

Note: ATP or adenosine triphosphate is a substance found in all living cells that is used to provide energy for many metabolic processes and also used for making RNA molecules. It is considered as a coenzyme that works with many enzymes inside our bodies.

Glucose is a simple sugar that is found in most foods. Cells use glucose to make energy, which they need to do everything from stay alive to carrying out important chemical reactions.

Krebs Cycle Diagram

The following diagram is Krebs cycle diagram in detail, showing the different steps, structures of the intermediates through the cycle, the enzymes and coenzymes which catalyze each step in the TCA cycle.

Krebs Cycle Steps

Now we will get all your questions answered with step by step explanations of Krebs cycle.

TCA cycle begins by breaking down pyruvate and releasing CO2 as a byproduct. This carbon can then enter different pathways depending on what type of molecule it bonds with, either O2 or NAD+. The results of this reaction are used for ATP formation as well as for acetyl CoA formation.

Look at the previous diagram and check the following steps!

Kreps cycle occurs over eight steps:

• Step 1 ( Citrate Formation)

  Acetyl CoA reacts with oxaloacetate in the presence of citrate synthase enzyme to form citrate or citric acid.

• Step 2 ( Citrate Isomers Formation)

In the second step, citric acid is first converted to an intermediate compound called cis-aconitate, then converted to isocitrate which is an isomer of citrate in the presence of aconitase enzyme.

• ·  Step 3 ( Isocitrate decarboxylation and oxidation)

In the third step, Isocitrate compound is oxidized to form alpha-ketoglutarate in the presence of isocitrate dehydrogenase enzyme. As a result of this step, carbon dioxide is released and a NADH molecule is formed.

• Step 4 ( Succinyl-CoA Formation)

In the fourth step, the Alpha-ketoglutarate compound is oxidized and binds to coenzyme A, to form succinyl CoA in the presence of a-Ketoglutarate Dehydrogenase enzyme which liberates:

•  Second molecule of NADH
•  Carbon dioxide
•  Proton

• Step 5 ( GTP Production)

In the fifth step, Succinyl CoA is converted to succinate compound in the presence of Succinyl-CoA synthetase enzyme which forms a molecule of GTP through the process of GDP phosphorylation. So we can consider that the result of this step is releasing GTP molecules, the Coenzyme A and also the formation of succinate.

•     Step 6 (Fumarate Formation)

In the sixth step, succinate compound is oxidized and converted to fumarate in the presence of Succinate Dehydrogenase enzyme. In this step, FADH₂ molecule is produced

• Step 7 ( Malate Formation)

In the seventh step, Fumarate compound is converted to malate in the presence of fumarase enzyme. In this step, H2O is incorporated to form the structure of the final product (malate) so we can consider fumarase enzyme as hydrolase enzyme.

• Step 8 (Oxaloacetate Formation)

In the eighth and final step, Malate compound is converted to oxaloacetate in the presence of malate Dehydrogenase enzyme. Here the NADH molecule no.3 in the cycle is produced.

We will explain the role of each enzyme in the following paragraphs.

Krebs Cycle Products

The Krebs cycle is a series of chemical reactions that allow cells to use energy from carbohydrates. The cycle starts with the entry of glucose into the cell. This energy is used for different cellular processes such as synthesizing proteins and membranes and sustaining cellular functions.

It  produces carbon dioxide and water as waste products. In order to use the energy from glucose for these processes, it has to be converted into another type of energy—in the form of adenosine triphosphate (ATP). This is the main form of energy storage in the cell and provides the cells with the energy they need to carry out various processes. The energy produced by the conversion of glucose into ATP is called cellular respiration. The Krebs cycle is an essential part of the process of cellular respiration.

The Krebs cycle also produces NADH and FADH₂ molecules, which are used in oxidative phosphorylation to produce ATP. It also produces two carbon dioxide molecules per turn (one CO2 is produced when 1 of the 4 carbons in the citric acid molecule is oxidized). The cycle produces 3 hydrogen ions (H+) during each turn.

So we can say that the net of each Krebs cycle products are:

•  3 NADH molecules.
• 1 FADH₂ molecule.
• 1 GTP molecule.
• 2 CO2 or carbon dioxide molecules.
• 3 (H+) hydrogen ions.

Note: In the case of 1 molecule of glucose, there are 2 acetyl-CoA molecules entering the Krebs cycle, so the total energy (products of the Krebs cycle) are duplicated into 6 NADH molecules /2 FADH₂ molecules / 2GTP molecules.

In the electron transport chain, each NADH molecule gives 2-3 ATPs and each FADH2 molecule forms 2 ATPs on oxidation

 Krebs Cycle Equation (Krebs cycle formula)

The following equation is the total Krebs cycle equation or the Krebs cycle formula which describes all the results compound:

2 acetyl groups + 6 NAD+ + 2 FAD + 2 ADP + 2 Pi + 2 H20————– 4CO2 + 6 NADH + 2 FADH2 + 2ATP + 2 CoA

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How Much ATP does the Krebs Cycle Produce?

The short answer is one molecule of ATP \ pyruvate molecule

Each molecule of pyruvate  enters citric acid cycle, forms one ATP molecule when succinyl-CoA converts to succinate in the presence of  Succinyl CoA synthetase enzyme. and there are 2 molecules of pyruvate results from the process of (one glucose) glycolysis.

So, we will have 2 molecules of ATP by the end of Krebs cycle.

 The Role of Enzymes in Krebs Cycle

Enzymes, which are proteins that catalyze chemical reactions in the body, are key players in the Krebs cycle and their role is essential for oxidative phosphorylation to occur. They regulate all the steps of the cycle.

The most well-known enzymes that are involved in the Krebs cycle:

• Citrate synthase enzyme

Citrate synthase removes the acetyl group and then adds it to oxaloacetate compound to form citric acid.

• Aconitase enzyme

Aconitase transfers an oxygen atom to make a more reactive molecule of isocitrate.

•  Isocitrate dehydrogenase enzyme

Isocitrate dehydrogenase removes only one carbon atom to form carbon dioxide CO2 and also transfers the electrons to the NADH molecule.

•   Alpha-Ketoglutarate Dehydrogenase enzyme

Alpha-Ketoglutarate Dehydrogenase removes only one carbon atom to form carbon dioxide CO2, also transfers the electrons to NADH molecule and the molecule remaining part is connected to coenzyme A.

•   Succinyl-CoA synthetase enzyme

Because the bond between coenzyme A and succinate is unstable and needed to provide the energy for building ATP molecule, the succinyl-CoA synthetase enzyme is used to create the GTP molecule in the reaction (fifth step).

•    Succinate Dehydrogenase enzyme

Succinate dehydrogenase plays a role in the electron transport chain by extracting the atoms of hydrogen from succinate compounds and transferring them to the FAD molecule which acts as carrier.

•  Fumarase enzyme

Fumarase adds a molecule of water to the molecule to prepare it for the last step of citric acid cycle.

•  Malate dehydrogenase enzyme

Malate dehydrogenase is used in the final step for oxaloacetate recreation and electrons transferring to NADH by converting malate compound to oxaloacetate compound.

Krebs Cycle Function

Krebs cycle or citric acid cycle plays a very important role in the production of energy and the molecules biosynthesis processes. The cycle ends the process of sugar-breaking which began in glycolysis and fuels the ATP production. It is also vital in the biosynthetic reactions by providing intermediates compounds that are used to synthesize important biological molecules like the amino acids. The cycle provides the electrons that fuel the oxidative phosphorylation process which is considered as the major source of energy and ATP.

Regulation of Krebs Cycle

The TCA Cycle is regulated by many factors:

• Enzymes, there are 3 major dehydrogenase enzymes are used for regulation in Krebs pathway:

– Pyruvate Dehydrogenase

– Isocitrate Dehydrogenase

                   – Alpha Ketoglutarate Dehydrogenase

•  Metabolites, such as NADH which inhibits the majority of the enzymes found in the Krebs cycle and can slow and stop the process of glycolysis before the release of too much energy by the process of gluconeogenesis.
•  Another important regulator is citrate, which inhibits phosphofructokinase and is considered as a very vital enzyme in the glycolysis process. citrate decreases the production of pyruvate and therefore acetyl-CoA (an important precursor for fat synthesis.)
• Calcium also plays a role in the regulation of the citric acid cycle as it stimulates the link reaction and then accelerates the cycle.

Fast Facts about Krebs Cycle

• The Krebs cycle is a cycle and a cyclic process. but it different from any other type of fuel cells as they are cyclic and rely on oxygen to synthesize energy instead of using oxygen transported by breathing.
• The Krebs cycle gets its name because it was discovered by a scientist named Hans Adolf Krebs in 1937.
• Krebs cycle is a metabolic pathway. It’s really a series of reactions that occur in both plant and animal cells.
• The Krebs Cycle describes the last step of cellular respiration wherein glucose, with the help of oxygen from the lungs or bloodstream, is broken down into carbon dioxide and water.
• In the first part of the cellular respiration, glycolysis occurs where one molecule of glucose converts into two molecules of pyruvate. These two molecules then enter the citric acid cycle which results in the formation of CO2, NADH and FADH2. They are then transported through oxidative phosphorylation to form ATP (producing 36 ATP per glucose molecule at maximum efficiency).
• Vitamins like thiamin, riboflavin, pantothenic and niacin play a vital role in the TCA cycle, as a part of various enzyme cofactors like FAD, NAD molecules and coenzyme A.
• Krebs cycle is known as an amphibolic (both anabolic and catabolic pathway)  process because in the cycle both anabolism and catabolism occur.
• The Krebs Cycle is a part of cellular respiration which helps cells break down food to create energy. This process is called oxidation. The food that we eat and drink provides our bodies with energy in the form of glucose.
• Glucose enters the cell by diffusion and this can occur at the plasma membrane or the lysosome membrane.
• Once the sugar molecule reaches the cell membrane, the cell membrane protein pumps the sugar into the cell, across the cell wall, and into the intracellular space. Once inside the cell, the sugar is broken down through a series of reactions “the citric acid cycle”. 

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 Explore the Krebs Cycle Online: Krebs Cycle Virtual Lab

Virtual lab simulations can provide a hands-on and immersive way to explore and understand Krebs cycle. Also, you can find interactive cellular respiration models to enrich your understanding of the cellular respiration process.

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