Urea cycle in tetrapods, fish and invertebrates. The first three enzymes of the urea cycle are localized in the mitochondria; the remaining three enzymes are cytoplasmic. Mammals and amphibians (tetrapods) have CPSI, which catalyzes the formation of CP from ammonia, bicarbonate and ATP. NAG is an essential allosteric activator of CPSI. CPSIII catalyzes the formation of CP from glutamine, bicarbonate and ATP in fish and invertebrates. The enzymatic activity of CPSIII increases in the presence of NAG. Abbreviations: NAGS – N-acetylglutamate synthase; NAG – N-acetylglutamate; CPSI – carbamylphosphate synthetase I; CPSIII – carbamylphosphate synthetase III; OTC – ornithine transcarbamylase; ASS – argininosuccinate synthase; ASL – argininosuccinate lyase.