The urea cycle is a vital metabolic pathway that converts toxic ammonia, produced during amino acid catabolism, into urea, which is less toxic and can be safely excreted in urine. This cycle occurs mainly in hepatocytes and involves reactions in both the mitochondrial matrix and cytosol. Ammonia arises from deamination of amino acids, intestinal bacterial activity, and other nitrogen-containing compounds, and even small increases in blood ammonia levels can be harmful to the central nervous system. The cycle begins in the mitochondria where free ammonia combines with carbon dioxide in the presence of carbamoyl phosphate synthetase I to form carbamoyl phosphate. This reaction requires two molecules of ATP and is activated by N-acetylglutamate, which acts as an essential allosteric activator. Carbamoyl phosphate then reacts with ornithine to form citrulline in a reaction catalyzed by ornithine transcarbamylase. Citrulline is transported out of the mitochondria into the cytosol, where it combines with aspartate, a second source of nitrogen,