The purpose of this review is to survey the literature on amino acid toxicities published since the extensive review of Harper et al (52) in 1970. The approach taken in that earlier review is followed here, and where possible we emphasize the development of animal models as related to inherited disorders, except in the discussions of methionine and the D-amino acids, where we focus on the supplementation of low-protein diets with free amino acids. There has been considerable recent progress in the understanding of the metabolic implications of high cellular concentrations of a number of amino acids; hence we have chosen to emphasize those amino acids. Recent reviews are available on the dicarboxylic acids (35, 40), so they are not included in this review. The metabolism of branched-chain amino acids is reviewed in another chapter in this volume.

As described earlier (52), adverse effects of consumption of excessive levels of amino acids can vary from a slight suppression of food intake, followed by an adaptation and return to normal food intake, to marked food intake suppres sion, massive tissue damage, and death. In many cases, the level of the amino acid in the diet can be adjusted so that marked food intake suppression as well as tissue histological changes can be seen, but if the animal continues to receive the diet it will adapt and gain weight, and the tissue histology will return to normal. In this review, the term toxicity generally refers to a marked alteration in food intake and/or tissue histology. A detailed description of amino acid imbalance, antagonisms, and toxicities, and ofthe impact of the diet and age of the animal on these is presented by Harper et al (52). We do not review the relative toxicities of the amino acids because recent evidence does not alter that published earlier (52).