Urea cycle

The urea cycle is the pathway that mammals use to dispose of the surplus nitrogen released when amino acids are broken down. Stripping the amino group from an amino acid yields ammonia, which is toxic, above all to the brain. Liver cells convert it into urea, a far safer, water-soluble compound that the blood carries to the kidneys for removal in urine. Hans Krebs and Kurt Henseleit first described the cycle in 1932.

The reactions are split between two parts of the liver cell. Inside mitochondria, ammonia and bicarbonate are joined into carbamoyl phosphate, which is then attached to the amino acid ornithine to form citrulline. Citrulline moves out to the cytosol, the fluid around the organelles, takes a second nitrogen atom from aspartate, and the product is split into fumarate and arginine. The enzyme arginase then cuts arginine into urea and ornithine, and the ornithine returns to the mitochondria to begin the next turn. Making each urea molecule costs three ATP, worth four high-energy phosphate bonds because one is split all the way to AMP, and the released fumarate connects the cycle to the citric acid cycle.

Inherited faults in any of the cycle's enzymes cause urea cycle disorders, in which ammonia builds up in the blood; the most common, ornithine transcarbamylase deficiency, is X-linked. Doctors also measure blood urea nitrogen as a routine marker of kidney function.