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Citric Acid (Krebs) Cycle – Products & Steps

The Citric Acid (Krebs) Cycle, also known as the TCA cycle, is a series of biochemical reactions that occur in the mitochondria of eukaryotic cells, and plays a critical role in the generation of ATP by oxidizing acetyl-CoA derived from carbohydrates, fats, and proteins. It is the second stage of cellular respiration.

This cycle is catalyzed by several enzymes and is named in honor of the British scientist Hans Krebs who identified the series of steps involved in the citric acid cycle.

The usable energy found in the carbohydrates, proteins, and fats we eat is released mainly through the citric acid cycle.

Although the citric acid cycle does not use oxygen directly, it works only when oxygen is present.

Step-1-Formation of Citrate

The first reaction of the cycle is the condensation of acetyl-CoA with oxaloacetate to form citrate, catalyzed by citrate synthase. Once oxaloacetate is joined with acetyl-CoA, a water molecule attacks the acetyl leading to the release of coenzyme A from the complex.

Step-2-Formation of Isocitrate

In this reaction, a water molecule is removed from the citric acid and then put back on in another location. The overall effect of this conversion is that the –OH group is moved from the 3′ to the 4′ position on the molecule. This transformation yields the molecule isocitrate.

Step-3- Formation of α- Keto Glutarate

In the third step, isocitrate is oxidized and releases a molecule of carbon dioxide, leaving behind a five-carbon molecule—α-keto glutarate. The enzyme catalyzing this step, isocitrate dehydrogenase, is important in regulating the speed of the citric acid cycle.

Step-4-Formation of Succinyl Co A

Alpha ketoglutarate is converted to the 4-carbon succinyl CoA. A molecule of CO2 is removed and NAD+ is reduced to NADH + H+ in the process. Enzyme: alpha ketoglutarate dehydrogenase.

Step-5- Formation of Succinate

The enzyme succinyl-CoA synthetase catalyzes the fifth reaction of the citric acid cycle. In this step a molecule of guanosine triphosphate (GTP) is synthesized. The four-carbon molecule produced in this step is called succinate.

Step-6- Formation of Fumarate

In step six, succinate is oxidized, forming another four-carbon molecule called fumarate.

Step-7- Formation of Malate

In step seven, water is added to the four-carbon molecule fumarate, converting it into another four-carbon molecule called malate.

Step-8- Regeneration of oxalo-acetate

Malate is oxidized to produce oxaloacetate, the starting compound of the citric acid cycle by malate dehydrogenase. During this oxidation, NAD+ is reduced to NADH + H+.

Read more about Pyruvate Oxidation


Illustration showing the Citric Acid (Krebs) Cycle

Frequently Asked Questions

What is the Krebs cycle?

It is a cycle of reactions taking place in the mitochondrial matrix. In this series of reactions, the acetyl CoA molecule is oxidized to release carbon dioxide and water with the formation of NADH and FADH2.

What are other names of the Krebs cycle?

It is also called the citric acid cycle or tricarboxylic acid cycle. 

How acetyl CoA enters the Krebs cycle?

It enters the Krebs cycle by reacting with the oxaloacetate forming citric acid or citrate. The coenzyme-A is released during this process.

What is the importance of the Krebs cycle?

It is the main source of energy for cells. It is an integral part of aerobic respiration in all organisms.