Ammonia is an essential nutrient, a component of all proteins, nucleic acids, and many key metabolites. In excess, it is a potent toxin. The free molecule is one of the most volatile and reactive radicals in physiological fluids, in dynamic equilibrium with ammonium, one of the most polar and reactive nonmetallic ions in physiological fluids. Its concentration in all fluid compartments is tightly controlled by intricately balanced enzyme and transport systems. These regulate its interconversions with several groups of precursors and derivatives (1-4).Elevations of ammonia can occur in several clinical situations, generally secondary to seriously impaired liver function. One of the most important problems in hepatology is the pathogenesis of encephalopathy in liver failure. Since Claude Bernard first introduced the concept of the milieu interieur and showed the important role played by the liver in its control, sorting out primary from secondary metabolic disturbances has remained a complex challenge. Experiments of nature, inherited blocks in metabolic pathways, provide unique opportunities to observe the role and importance of each pathway, and to study the effects of primary ammonia excess on various metabolic functions, uncomplicated by nonspecific liver damage (3, 5-7).This review updates recent information about inherited and noninherited disorders that produce hyperammonemia. It will focus on the biochemical mechanisms leading to ammonia accumulation, its toxicity, and how these disorders have responded to various therapeutic approaches. Important historical data and clinical details, which have been extensively reviewed elsewhere, will be covered only briefly here (1, 3, 4, 6, 7).
