The urea cycle and related reactions of ammonia metabolism. Congenital hyperammonemia syndromes usually are caused by a deficiency of one of the enzymes of the urea cycle. Ammonia also can be metabolized to glutamate, alanine, glutamine and glycine. Administration of phenylacetate or of benzoate favors the formation of phenylacetylglutamine and hippurate, respectively, thereby providing an effective “antidote” to ammonia toxicity. Enzymes: 1, carbamyl phosphate synthetase; 2, ornithine transcarbamylase; 3, argininosuccinate synthetase; 4, argininosuccinate lyase; 5, arginase; 6, glutamine synthetase; 7, glycine-cleavage system; 8, glycine-N-acylase; 9, glutamate dehydrogenase; 10, alanine aminotransferase; 11, cytosolic pathway of orotic acid synthesis, which becomes prominent when there is a block at the level of reaction 2, thus resulting in increased orotic acid excretion; 12, N-acetylglutamate synthetase; 13, phenylacetyl-CoA:glutamine transferase. NAG, N-acetylglutamate; PA-CoA, phenylacetyl-CoA; GLN, glutamine. The + symbols denote that arginine and NAG are positive effectors for reactions 12 and 1, respectively.