Urea cycle

File:Urea cycle.svg

Diagram of the urea cycle

File:Urea-Cycle scheme 2006-01.svg

Alternative schematic of the urea cycle

Another representation of the urea cycle

The urea cycle is a series of biochemical reactions that produce urea ((NH_)_CO) from ammonia (NH_). This cycle occurs in the liver and is essential for the removal of excess nitrogen from the body. The urea cycle is also known as the ornithine cycle, named after one of its key intermediates, ornithine.

History

The urea cycle was the first metabolic cycle to be discovered, identified by Hans Krebs and Kurt Henseleit in 1932. This discovery was pivotal in understanding how organisms detoxify ammonia, a byproduct of protein metabolism.

Biochemical Pathway

The urea cycle consists of five main steps, each catalyzed by a specific enzyme:

1. Carbamoyl phosphate synthetase I: This enzyme catalyzes the reaction of ammonia with bicarbonate to form carbamoyl phosphate. This step occurs in the mitochondria.
2. Ornithine transcarbamylase: Carbamoyl phosphate reacts with ornithine to form citrulline, which is then transported out of the mitochondria.
3. Argininosuccinate synthetase: Citrulline combines with aspartate to form argininosuccinate.
4. Argininosuccinate lyase: Argininosuccinate is cleaved to form arginine and fumarate.
5. Arginase: Arginine is hydrolyzed to form urea and regenerate ornithine, which re-enters the cycle.

Regulation

The urea cycle is regulated by the availability of its substrates and by the activity of its enzymes. N-acetylglutamate acts as an essential activator of carbamoyl phosphate synthetase I, thus playing a crucial role in the regulation of the cycle.

Clinical Significance

Deficiencies in any of the enzymes of the urea cycle can lead to urea cycle disorders, which result in the accumulation of ammonia in the blood, a condition known as hyperammonemia. Symptoms can range from mild to severe and may include lethargy, vomiting, and in severe cases, neurological damage.

Related Pages

• Ammonia
• Liver
• Metabolism
• Ornithine

References

• Krebs, H. A., & Henseleit, K. (1932). "Studies on the urea cycle." *Biochemische Zeitschrift*, 210, 33-66.
• Brusilow, S. W., & Horwich, A. L. (2001). "Urea cycle enzymes." In *The Metabolic and Molecular Bases of Inherited Disease* (8th ed.).