He urea cycle is a procedure through which the body converts the ammonium into urea and removes it from the body through the urine.
Ammonium is a compound 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 particularities of this cycle together with the biochemist Kurt Henseleit, also German, who was his collaborator. This discovery was carried out in 1932.
All the living beings they need to discard the excess nitrogen from their organisms. However, not everyone excretes it in the same way. Aquatic beings discard this compound as ammonium; for this reason they are called amonotélicos organisms.
Reptiles and most birds release nitrogen from the body in the form of uric acid; given this characteristic, are classified among the uricotélicos organisms.
In the case of terrestrial vertebrates, most of these discard the excesses of nitrogen in the form of urea, which is why they are called ureotlics.
If ammonium is not removed through the urea cycle, it can accumulate in the blood, which generates a syndrome called hyperammonemia, which can lead to fatal consequences.
For this reason, it is very important that there is a fluid urea cycle, to avoid toxic reactions in the body.
Stages of the urea cycle
The urea cycle is carried out in the liver. It comprises five different processes and in these procedures different enzymes that perform the necessary conversions are involved.
Through these conversions, the expulsion of ammonium generated in the organism is achieved as a consequence of the nitrogen metabolism in the body.
The characteristics of each of the five stages of the urea cycle will be detailed below:
First phase
The process begins in the mitochondria , cellular organ whose function is to produce energy during the process of cellular respiration.
In mitochondria a first amino group is produced which is derived from ammonia. Mitochondria contain bicarbonate, which is generated as a result of cellular respiration.
This bicarbonate is bound to ammonia and, through the participation of the enzyme carbamoyl-phosphate-synthetase I, which generates carbamoyl-phosphate.
Second stage
In this phase appears another compound: an amino acid called ornithine, whose main function is to act in the detoxification of the organism.
The carbamoyl phosphate will deliver the carbamoyl to ornithine, and from that fusion will generate citrulline, another amino acid that has the function of promoting vasodilation, among other tasks. In this particular case, citrulline will be an intermediate in the urea cycle.
The formation of citrulline is performed 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 is displaced into the cytoplasm of the cell.
Third phase
In addition to ammonia, in the mitochondria arises a second amino group derived from aspartate, an amino acid that has multiple functions, including nitrogen transport.
Aspartate binds to citrulline and argininosuccinate is generated.
Fourth phase
In the fourth phase, argininosuccinate reacts as a result of the action of the enzyme argininosuccinate lyase, which results in two compounds: free arginine, which, among other functions, is responsible for lowering blood pressure; and fumarate, also called fumaric acid.
Fifth stage
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.
It is possible that ornithine is transferred 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, ammonium is converted to urea through the cycle explained above. Ammonium 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 ammonium and avoid the difficulties, in many cases fatal, that are linked to the accumulation of this element highly toxic to 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 difficulty in disposing of the ammonium and ends up accumulating it both in the blood and in the brain.
This phenomenon is known as hyperammonemia, and is referred to high levels of ammonium in the body.
Failures in the synthesis of some enzymes are inherited, which can lead to congenital disorders in the metabolic area. A child may be born with disorders in the urea cycle as a result of erroneous genetic information.
If this occurs, the child will have trouble disposing of the ammonia, accumulating it and becoming intoxicated with it.
The symptoms you may have may be mild, such as vomiting or food rejection, but they can also be more severe, even generating a coma.
Treatment
To avoid fatal scenarios in children with disorders in the urea cycle, it is necessary to identify the situation as early as possible and avoid ammonia intoxication through careful choice of diet that will be most convenient.
In this diet must be restricted natural proteins, because when the child ingests the amino acids are released, they release ammonia and can not be synthesized naturally by the body, which will generate hyperammonemia.
People suffering from syndromes in the urea cycle can lead a fairly normal life, only with restrictions in the food field.
References
- Vásquez-Contreras, E."Urea Cycle"(19 September 2003) in Department of Biochemistry UNAM. Retrieved on 12 September 2017 of Department of Biochemistry UNAM: bq.facmed.unam.mx
- "Cycle of urea"in Catalan Association of Metabolic Hereditary Disorders. Retrieved on 12 September 2017 of Catalan Association of Metabolic Disorders: pkuatm.org
- "Destination of amino group 2. Urea cycle: Reactions and regulation"(2006) at University of Alcalá. Retrieved on 12 September 2017 from Universidad de Alcalá: uah.es
- "What is a Urea Cycle Disorder?"At the National Urea Cycle Disorders Foundation. Retrieved on 12 September 2017 from National Urea Cycle Disorders Foundation: nucdf.org
- Siegel, G., Agranoff, B. and Albers, R."Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition"(1999) at National Center of Biotechnology Information. Retrieved on 12 September 2017 from National Center of Biotechnology Information: ncbi.nlm.nih.gov
- "Citrulina: functions and contraindications"(November 28, 2016) at the IAF Store. Retrieved on September 12, 2017 from IAF Store: blog.iafstore.com
- "Ornithine"in Aminoacid. Retrieved on 12 September 2017 from Aminoacido: aminoacido.eu
- "Aspartate"(20 April 2017) in NaturSanix. Recovered on September 12, 2017 by NaturSanix: natursanix.com
- "Arginine"in Aminoacid. Retrieved on 12 September 2017 from Aminoacido: aminoacido.eu.