Urea is the major end product of nitrogen metabolism in humans
and mammals. Ammonia, the product of oxidative deamination reactions,
is toxic in even small amounts and must be removed from the body.
The urea cycle or the ornithine cycle describes the conversion
reactions of ammonia into urea. Since these reactions occur in
the liver, the urea is then transported to the kidneys where
it is excreted. The overall urea formation reaction is:
2 Ammonia + carbon dioxide + 3ATP ---> urea + water + 3
The step wise process of the urea cycle is summarized in the
graphic on the left. One amine group comes from oxidative deamination
of glutamic acid while the other amine group comes from aspartic
acid. Aspartic acid is regenerated from fumaric acid produced
by the urea cycle. The fumaric acid first undergoes reactions
through a portion of the citric acid cycle to produce oxaloacetic
acid which is then changed by transamination into aspartic acid.
Link to: Urea
Cycle (move cursor over arrows)
Jim Hardy, Professor of Chemistry, The University of Akron.
Urea is routinely measured in the blood as: Blood Urea
Nitrogen (BUN). BUN levels may be elevated (a condition
called uremia) in both acute and chronic renal (kidney) failure.
Various diseases damage the kidney and cause faulty urine formation
and excretion. Congestive heart failure leads to a low blood
pressure and consequent reduced filtration rates through the
kidneys, therefore, BUN may be elevated. Urinary tract obstructions
can also lead to an increased BUN. In severe cases, hemodialysis
is used to remove the soluble urea and other waste products from
the blood. Waste products diffuse through the dialyzing membrane
because their concentration is lower in the dialyzing solution.
Ions, such as Na+ and Cl- which are to
remain in the blood, are maintained at the same concentration
in the dialyzing solution - no net diffusion occurs.
As stated previously, high ammonia levels are toxic to humans.
A complete block of any step in the urea cycle is fatal since
there is no known alternative pathway for the synthesis of urea.
Inherited disorders from defective enzymes may cause a partial
block in some of the reactions and results in hyperammonemia
which can lead to mental retardation. Extensive ammonia accumulation
leads to extensive liver damage and death. Liver cirrhosis caused
by alcoholism creates an interference in the enzymes which produce
carbamyl phosphate in the first step on the cycle.