Urea cycle

The ureosynthetic cycle (urea, ornithine) is used to break down nitrogen from the body with the help of hydrophilic urea. Urea is then excreted together with the urine out of the body and the body is thus rid of toxic ammonia.

Urea cycle in general

The urea cycle takes place only in the liver, where ammonia reacts with other cycle components. The product is urea, which travels through the bloodstream to the kidneys, where it is excreted in the aqueous environment. At the cellular level, two stages are distinguished in the cycle – in mitochondria and in the cytosol.

The source of ammonia is mainly ``amino acids, partially metabolism of purines and pyrimidines, synthesis of hemeu or colon bacteria.

The elimination of toxic ammonia is absolutely essential for the survival of the individual. NH₃ molecules are toxic to the body and even a small concentration can be fatal. The brain is most sensitive to the concentration of ammonia in the blood. Nitrogen is therefore transported embedded in amino acids (glutamate) or in the non-toxic protonated form NH₄⁺. The form in which ammonia is found also depends on pH.

Urea cycle disorders are accompanied by neurological symptoms ranging from mild to mental retardation, impaired consciousness, and death.

Individual reactions

Scheme of reactions: 1 - ornithine, 2 - carbamoyl phosphate, 3 - citrulline, 4 - argininosuccinate, 5 - fumarate, 6 - arginine, 7 - urea, L-Asp ' – L-aspartate, CPS-1 – carbamoyl phosphate synthetase, OTC – ornithine carbamoyltransferase, ASS – arginine succinate synthetase, ASL – arginine succinase, 'ARG1 – arginase

The urea cycle consists of these reactions:

1. Ammonia entry into the ornithine cycle:
   • NH₃ + CO₂ + 2ATP → carbamoyl phosphate + Pi + 2ADP
   • catalyzed by the enzyme carbamoylphosphate synthase'', which requires the presence of Mg²⁺ and N-acetylglutamate for its activity
   • takes place in the mitochondria matrix'
2. Carbamoyl phosphate reaction with ornithine:
   • carbamoyl phosphate + ornithine → citrulline + Pi
   • catalyzed by L-ornithine-carbamoyltransferase'
   • takes place in the mitochondria matrix'
3. Citrulline and aspartate reaction
   • citrulline + ATP + aspartate → argininosuccinate + AMP + PPi
   • catalyzes arginine succinate synthetase'
   • takes place in cytosol
4. Argininosuccinate cleavage
   • argininosuccinate Template:Reverse reaction arginine + fumarate
   • catalyzes argininsuccinase'
   • takes place in cytosol
   • fumarate may participate in the citrate cycle
5. Urea formation
   • arginine → ornithine + urea
   • catalyzes argininase'
   • takes place in cytosol
   • urea passes into the blood, ornithine returns to the mitochondrial matrix

Regulation of the urea cycle

The cycle is regulated by:

• the activity of carbamoyl phosphate synthase is under the influence of the allosteric effector N-acetylglutamate
• concentration of ornithine' in mitochondria for the first step of the cycle
• increased or decreased 'degradation of amino acids

Links

Related Articles

• ws:Močovinový cyklus
• Urea cycle disorders
• Amino Acids
• Urea

References

• KIDNEY, Miroslav, et al. Biochemistry for medical students. Part I. 2. edition. Prague : Karolinum, 2009. 269 pp. pp. 226-228. ISBN 978-80-246-1416-8.

• MURRAY, Robert K. Harper's Biochemistry. 2. edition. Jinocany : H&H, 2002. pp. 312-315. ISBN 80-7319-013-3.