The urea cycle describes how liver cells convert ammonia to urea. Ammonia is a toxic waste product of protein catabolism. Land animals must convert ammonia into the less toxic urea which can be safely eliminated by the kidneys through urine. Marine animals excrete ammonia directly, and the surrounding water dilutes the ammonia to safe levels.
There are five basic steps in the urea cycle:
Notice that ornithine is used in the second step and is regenerated in the last step. Since ornithine is recycled, the urea cycle is sometimes referred to as the ornithine cycle.
Elevated levels of blood ammonia, or hyperammonemia, results from an interruption of the urea cycle. This can occur at the organ level where scar tissue blocks the blood supply to the liver. Scar tissue, or cirrhosis, can result from chronic alcohol abuse, hepatitis B, or hepatitis C infection.
Within the liver cells, disruption of the urea cycle can also occur in any one of its five steps. Ornithine transcarbamylase deficiency (OTCD) is an inherited metabolic disorder that results in a full or partial enzyme deficiency in step 2, affecting the production of citrulline from ornithine and carbamoyl phosphate.
Hyperammonemia in adults, resulting from cirrhosis or late-onset metabolic disorders, can result in deficits in attention and other cognitive impairments. They are also at higher risk of death from liver failure. In neonates with early-onset enzyme deficiency, developmental delays can be expected. If not diagnosed and treated, these infants risk coma and death. How elevated ammonia damages the brain to produce cognitive and developmental delays is not yet fully understood; however, disturbances in amino acid and neurotransmitter levels, disruptions in ion channel function, and energy deficits in the brain have been proposed as possible mechanisms.
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