urea cycle

The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions occurring in many animals that produces urea (NH2)2CO from ammonia (NH3). This cycle was the first metabolic cycle discovered (Hans Krebs and Kurt Henseleit, 1932). In mammals, the urea cycle takes place only in the liver.

Organisms that cannot easily and quickly remove ammonia usually have to convert it to some other substance, like urea or uric acid, which are much less toxic.

The urea cycle consists of five reactions - two mitochondrial and three cytosolic. The cycle converts two amino groups, one from NH4+ and one from Asp, and a carbon atom from HCO3-, to relatively nontoxic excretion product, urea, at the cost of four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP). Orn is the carrier of these carbon and nitrogen atoms.

Pathology

 hepatic encephalopathy

Insufficiency of the urea cycle occurs in some genetic disorders (inborn errors of metabolism), and in liver failure.

The result of liver failure is accumulation of nitrogenous waste, mainly ammonia, which leads to hepatic encephalopathy.

 urea cycle diseases

• ornithine transcarbamylase deficiency
• carbamoyl phosphate synthetase deficiency (Ornithine translocase deficiency)
• argininosuccinic aciduria
• argininemia
• hyperornithinemia, hyperammonemia, homocitrullinuria syndrome (HHH syndrome)
• lysinuric protein intolerance
• citrullinemia
• N-acetylglutamate synthase deficiency

Most of them are associated with hyperammonemia.