UREA CYCLE: PHASES, CHARACTERISTICS AND IMPORTANCE - BIOLOGY - 2025

The urea cycle is a procedure in which the body converts ammonia to urea and removes it from the body through urine.

Ammonium is a compound that is a product of nitrogen metabolism, which is released by amino acids from protein degradation. Ammonium is quite toxic and the body has a natural mechanism to remove it from the system.

The urea cycle is also called the Krebs-Henseleit cycle, in honor of the German biochemist Hans Adolf Krebs, who discovered and characterized the phases and peculiarities of this cycle together with the biochemist Kurt Henseleit, also German, who was his collaborator. This discovery was made in 1932.

All living things need to get rid of excess nitrogen from their bodies. However, not everyone excretes it in the same way. Aquatic beings dispose of this compound in the form of ammonium; for this reason they are called ammonothelial organisms.

Reptiles and most birds release nitrogen from the body in the form of uric acid; given this characteristic, they are classified among uricotelic organisms.

In the case of terrestrial vertebrates, most of these discard excess nitrogen in the form of urea, which is why they are called ureotelic.

If ammonia is not removed through the urea cycle, it can build up in the blood, creating a syndrome called hyperammonemia, which can lead to fatal consequences.

For this reason, it is very important that there is a fluid urea cycle, in order to avoid toxic reactions in the body.

Phases of the urea cycle

The urea cycle takes place in the liver. It comprises five different processes and different enzymes participate in these procedures that carry out the necessary conversions.

Through these conversions, the ammonium generated in the body as a consequence of nitrogen metabolism in the body is expelled.

The characteristics of each of the five stages of the urea cycle will be detailed below:

First phase

The process begins in the mitochondria, a cellular organ whose function is to produce energy during the process of cellular respiration.

A first amino group is produced in the mitochondria and is derived from ammonia. Mitochondria contain bicarbonate, which is generated as a result of cellular respiration.

Said bicarbonate binds to ammonia and, through the participation of the enzyme carbamoyl-phosphate-synthetase I, which generates carbamoyl-phosphate.

Second stage

In this phase another compound appears: an amino acid called ornithine, whose main function is to act in the detoxification of the body.

The carbamoyl-phosphate will deliver the carbamoyl to the ornithine, and from this fusion, citrulline will be generated, another amino acid whose function is to promote vasodilation, among other tasks. In this particular case, citrulline will be an intermediate in the urea cycle.

The formation of citrulline is carried out through the participation of an enzyme called ornithine transcarbamylase which, in addition to generating citrulline, also releases phosphate.

The citrulline released in this second phase moves to the cytoplasm of the cell.

Third phase

In addition to ammonia, a second amino group derived from aspartate arises in the mitochondria, an amino acid that has multiple functions, among which nitrogen transport stands out.

Aspartate binds to citrulline and argininosuccinate is generated.

Fourth phase

In the fourth phase, argininosuccinate reacts as a consequence of the action of the enzyme argininosuccinate lyase, resulting in two compounds: free arginine, which, among other functions, is responsible for lowering blood pressure; and fumarate, also called fumaric acid.

Fifth phase

In the last phase of the urea cycle, arginine reacts to the action of the enzyme arginase, which results in the appearance of urea and ornithine.

Ornithine may move back into the mitochondria, to start the cycle from the first phase, and urea is ready to be expelled from the body.

Importance of the urea cycle

As already seen, ammonia is converted to urea through the cycle explained above. Ammonia is highly toxic to the body, so it needs to be expelled from the body.

Thanks to the action of enzymes in the urea cycle, the body is able to dispose of ammonia and avoid the difficulties, in many cases fatal, that are linked to the accumulation of this highly toxic element for the body.

Disorders in the urea cycle

It may happen that the ammonium-degrading enzymes do not work properly. If this happens, the body has a hard time getting rid of ammonia and ends up accumulating it both in the blood and in the brain.

This phenomenon is known as hyperammonemia, and it refers to high levels of ammonia in the body.

Failures in the synthesis of some enzymes are hereditary, which is why it can generate congenital disorders in the metabolic field. It is possible for a child to be born with urea cycle disorders as a result of misleading genetic information.

If this happens, the child will have trouble getting rid of the ammonia, it will accumulate and may become intoxicated with it.

The symptoms that you will present can be mild, such as vomiting or refusing food, but they can also be more serious, even generating a coma.

Treatment

To avoid fatal scenarios in children who present disorders in the urea cycle, it is necessary to identify the situation as early as possible, and avoid ammonium poisoning by carefully choosing the diet that will be most convenient for them.

In this diet, natural proteins must be restricted, because when the child ingests them, their own amino acids are released, which will release ammonia and cannot be synthesized naturally by the body, thus generating hyperammonemia.

People with urea cycle syndromes can lead fairly normal lives, only with dietary restrictions.

References

1. Vásquez-Contreras, E. "Urea Cycle" (September 19, 2003) in the Department of Biochemistry UNAM. Retrieved on September 12, 2017 from the UNAM Department of Biochemistry: bq.facmed.unam.mx
2. "Urea cycle" in the Catalan Association of Hereditary Metabolic Disorders. Retrieved on September 12, 2017 from the Catalan Association of Hereditary Metabolic Disorders: pkuatm.org
3. "Fate of the amino group 2. Urea cycle: Reactions and regulation" (2006) at the University of Alcalá. Retrieved on September 12, 2017 from the University of Alcalá: uah.es
4. "What is a Urea Cycle Disorder?" at the National Urea Cycle Disorders Foundation. Retrieved on September 12, 2017 from the National Urea Cycle Disorders Foundation: nucdf.org
5. Siegel, G., Agranoff, B. and Albers, R. “Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition ”(1999) in National Center of Biotechnology Information. Retrieved on September 12, 2017 from the National Center of Biotechnology Information: ncbi.nlm.nih.gov
6. "Citrulline: functions and contraindications" (November 28, 2016) at IAF Store. Retrieved on September 12, 2017 from IAF Store: blog.iafstore.com
7. "Ornithine" in Amino Acid. Recovered on September 12, 2017 from Aminoacido: aminoacido.eu
8. "Aspartate" (April 20, 2017) in NaturSanix. Retrieved on September 12, 2017 from NaturSanix: natursanix.com
9. "Arginine" in Amino Acid. Retrieved on September 12, 2017 from Aminoacido: aminoacido.eu.