Which organ is primarily responsible for detoxifying ammonia by converting it to urea in the urea cycle?

• A. Kidneys
• B. Lungs
• C. Liver
• D. Spleen

Answer: (C)

Ammonia detoxification through the urea cycle is carried out mainly in the liver. In hepatocytes, ammonia—a highly toxic molecule—enters the mitochondria and is converted first to carbamoyl phosphate by carbamoyl phosphate synthetase I, then through a series of enzymatic steps that produce urea. This urea is released into the bloodstream and ultimately excreted by the kidneys. The liver is equipped with the full set of urea cycle enzymes and the regulatory chemistry (including activation by N-acetylglutamate), which explains why it’s the primary site for this detoxification. The lungs mainly manage gas exchange (removing CO2) and do not convert ammonia to urea, and the spleen isn’t involved in nitrogen metabolism, so they don’t play a primary role in this detoxification process.