Steps and Reactions Involved in the Krebs Cycle

The Krebs cycle, also known as the citric acid cycle or the tricarboxylic acid (TCA) cycle, is a crucial metabolic pathway that occurs in the mitochondria of eukaryotic cells. Named after its discoverer, Sir Hans Krebs, this cycle plays a fundamental role in the aerobic respiration process, generating energy-rich molecules that fuel cellular activities. In this article, we will explore the steps and reactions involved in the Krebs cycle, unraveling the intricacies of this vital metabolic pathway.

Overview of the Krebs Cycle

The Krebs cycle is a series of chemical reactions that take place in the matrix of the mitochondria. It involves the complete oxidation of acetyl-CoA, a two-carbon molecule derived from the breakdown of glucose, fatty acids, or amino acids. The cycle consists of eight steps, each catalyzed by a specific enzyme, and produces energy-rich molecules in the form of ATP, NADH, FADH2, and CO2.

The overall reaction of the Krebs cycle can be summarized as follows:

Acetyl-CoA + 3NAD+ + FAD + GDP + Pi + 2H2O → 2CO2 + 3NADH + FADH2 + GTP + 3H+ + CoA

Now, let’s dive into each step of the Krebs cycle and explore the reactions involved.

Step 1: Formation of Citrate

The first step of the Krebs cycle involves the condensation of acetyl-CoA with oxaloacetate, a four-carbon molecule, to form citrate, a six-carbon molecule. This reaction is catalyzed by the enzyme citrate synthase.

Acetyl-CoA + Oxaloacetate → Citrate + CoA-SH

Step 2: Isomerization of Citrate

In the second step, the enzyme aconitase catalyzes the conversion of citrate into isocitrate through an isomerization reaction.

Citrate → Isocitrate

Step 3: Oxidative Decarboxylation of Isocitrate

Isocitrate is then oxidatively decarboxylated by the enzyme isocitrate dehydrogenase, producing alpha-ketoglutarate, NADH, and CO2.

Isocitrate + NAD+ → alpha-Ketoglutarate + NADH + CO2

Step 4: Oxidative Decarboxylation of Alpha-Ketoglutarate

The enzyme alpha-ketoglutarate dehydrogenase catalyzes the oxidative decarboxylation of alpha-ketoglutarate, generating NADH, CO2, and succinyl-CoA.

alpha-Ketoglutarate + NAD+ + CoA-SH → Succinyl-CoA + NADH + CO2

Step 5: Conversion of Succinyl-CoA to Succinate

In this step, succinyl-CoA is converted to succinate with the help of the enzyme succinyl-CoA synthetase. This reaction also leads to the production of GTP (which can be converted to ATP) and CoA-SH.

Succinyl-CoA + GDP + Pi → Succinate + GTP + CoA-SH

Step 6: Oxidation of Succinate to Fumarate

The enzyme succinate dehydrogenase catalyzes the oxidation of succinate to fumarate, generating FADH2 in the process.

Succinate + FAD → Fumarate + FADH2

Step 7: Hydration of Fumarate

Fumarate is hydrated to form malate in the presence of the enzyme fumarase.

Fumarate + H2O → Malate

Step 8: Oxidation of Malate to Oxaloacetate

The final step of the Krebs cycle involves the oxidation of malate to oxaloacetate by the enzyme malate dehydrogenase. This reaction generates NADH and completes the cycle, as oxaloacetate can then combine with another acetyl-CoA to initiate the cycle again.

Malate + NAD+ → Oxaloacetate + NADH + H+

Significance of the Krebs Cycle

The Krebs cycle is a central component of cellular respiration and plays a crucial role in the generation of ATP, the energy currency of cells. It not only produces energy-rich molecules like NADH and FADH2 but also provides intermediates for other metabolic pathways. The cycle also serves as a key connection between carbohydrate, lipid, and protein metabolism, as the breakdown products of these macromolecules can enter the Krebs cycle and be oxidized for energy production.

Frequently Asked Questions (FAQ)

Q1: What is the primary purpose of the Krebs cycle?
The primary purpose of the Krebs cycle is to generate energy-rich molecules, such as ATP, NADH, and FADH2, through the oxidation of acetyl-CoA.

Q2: How is the Krebs cycle regulated?
The Krebs cycle is regulated by various mechanisms, including feedback inhibition and the availability of substrates. High levels of ATP and NADH can inhibit key enzymes in the cycle, while low levels of substrates, such as oxaloacetate, can limit its activity.

Q3: Can the Krebs cycle occur without oxygen?
No, the Krebs cycle is an aerobic process that requires oxygen as the final electron acceptor. Without oxygen, the cycle cannot proceed, and alternative metabolic pathways, such as fermentation, may take place.

Q4: What happens to the carbon atoms in the Krebs cycle?
During the Krebs cycle, two carbon atoms from acetyl-CoA are released as carbon dioxide (CO2) in multiple steps. This carbon dioxide is a waste product that is expelled from the body through respiration.

Q5: How does the Krebs cycle connect to other metabolic pathways?
The Krebs cycle is interconnected with other metabolic pathways. For example, the intermediates of the cycle can be used for the synthesis of amino acids, nucleotides, and other important molecules. Additionally, the NADH and FADH2 produced in the cycle are used in the electron transport chain to generate more ATP.


The Krebs cycle is a complex and essential metabolic pathway that plays a central role in cellular respiration. Through a series of enzymatic reactions, it converts acetyl-CoA into energy-rich molecules, such as ATP, NADH, and FADH2. The cycle not only generates energy but also provides intermediates for other metabolic processes. Understanding the steps and reactions involved in the Krebs cycle is crucial for comprehending the intricate workings of cellular metabolism.

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