Some of the ammonia formed in the breakdown of amino acids is consumed in the biosynthesis of nitrogen compounds. In most terrestrial vertebrates, the excess NH₄⁺ is converted into urea and then excreted, detoxificating the organism. This proccess, the urea cycle, is based on the convertion of ornithine to arginine by diverse steps. The urea is released in the step of regeneration of the ornithine from arginine.

The urea cycle begins in the hepatic cells mitochondria (five enzymes) but three steps occur in the cytosol.

Since the urea molecule has two nitrogens and one carbon atom, two amino groups must enter in the cycle: the first one is derived from ammonia and the other one is transferred from an amino acid, aspartate. The carbon atom comes from CO_2, (in the HCO₃^- form), used to synthesize carbamoyl-P by the condensation with NH₄⁺. There are three sources of ammonia: free ammonia in the mitochondria; derived from deamination; or from the bacterial oxidation of amino acids in the intestine, brought to the liver by the portal vein.

The carbamoyl group has a high transfer potential because of its anhydride bond, and is so used to transfer the amino group to ornithine, starting the cycle.

Since the remaining urea cycle reactions occur in the cytosol, citrulline must be exported from the mitochondria. But it's tranfered directly to the active site of the enzyme argininesuccinate synthetase. This indicates that the mitochondrial and cytosolic enzymes of the urea cycle are linked. Only the final product - urea - is released in the cytosol solution.

The final energetic cost is very high, since 4 ATPs are invested to synthesize just one urea molecule.

The Citric Acid Cycle and the Urea Cycle are linked

Alternatives nitrogen excretion

Living organisms excrete the excess nitrogen resulting from the metabolic breakdown of amino acids in one of three ways. Many aquatic animals simple excrete ammnoia. Where water is less plentiful, however, processes have evolved that convert ammonia to less toxic waste products that therefore require less water for excretion. One such product is urea, wich is excreted by most terrestrial vertebrates. This less toxicity makes the energetic cost worth. Another product is uric acid, wich is excreted by birds and terrestrial reptiles.