Ammonia in Liver and Extrahepatic Tissues: An Overview of Metabolism and Toxicity in Mammals

Ammonia is a major byproduct of systemic and cerebral nitrogen metabolism and is generated in at least 20 enzymatic reactions within the major organs of the body. Ammonia is thought to be generated in the gastrointestinal tract by the action of bacteria on nitrogenous substrates and by deamidation of glutamine in the large and small intestine. Substantial amounts of ammonia are generated in the liver from glutamate and in the kidney by deamidation of glutamine. The principal fate of systemic blood ammonia, in the brain and other organs, is incorporation into glutamine (amide). Portal vein ammonia (which is present at a much higher concentration (~0.5–1.0 mM) than in the peripheral arterial or venous (20–110 μM) blood), on the other hand, is largely detoxified as urea in the liver. The glutamine derived from brain, muscle and other tissues acts as an energy source for the gut and at the same time releases ammonia for urea synthesis. Thus, ultimately, most extrahepatic ammonia is incorporated into urea by temporary storage in glutamine (amide).