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Studies on the Toxicity and Antagonism of Amino Acids for Weanling Rats^1,2,

Department of Animal Science, Agricultural Experiment Station, Auburn University, Auburn, Alabama

The toxicity of 19 amino acids when fed individually in excess (5% level) in a low-protein diet was studied with weanling rats. With the exception of alanine, all amino acids tested produced depressions in growth to varying degrees. Methionine produced the severest growth depressions followed in decreasing order by tryptophan, DL-aspartic acid, histidine, tyrosine, phenylalanine, cystine, leucine, valine, isoleucine, glycine, asparagine, arginine, L-aspartic acid, lysine and threonine. Glutamic acid, proline and serine produced only slight growth depressions.

Results of studies on the isomers of several amino acids indicated that the D-isomers usually produced less inhibition in growth than the corresponding L-form. DL-Aspartic acid, however, produced greater detrimental effects than L-aspartic acid.

The growth depression of the several amino acids studied could be partially or completely prevented by supplements of protein to the diet. The degree of toxicity of the amino acids was dependent also upon the specific protein fed the animals.

L-Cystine at a level of 5% in a low-protein diet depressed growth and produced some deaths. When the casein in the high-cystine diet was increased to a level of 36%, the number of deaths was greatly increased. When lactalbumin was fed in place of casein, however, no deaths occurred and growth was nearly normal.

Supplements of leucine or of hemoglobin to a corn grain basal diet produced a severe depression in growth. The effect was partially-to-completely reversed by supplements of isoleucine.

Analyses of the plasma usually demonstrated high values for free amino acid content of the amino acid supplemented in excess in the diet. However, the toxicity of several amino acids did not appear to be directly related to their plasma concentration.

² These studies were supported by the National Institutes of Health, grant A-1175 and by the Williams-Waterman Fund of the Research Corporation. Appreciation is expressed to A. E. Staley Manufacturing Company for inositol, to Lederle Laboratories for folic acid, to Merck and Company for the other vitamins used in this study and to the Dow Chemical Company and E. I. duPont de Nemours and Company for amino acids.

³ Present address: U. S. Army Medical Research and Nutrition Laboratory, Fitzsimons General Hospital, Denver 30, Colorado.

Manuscript received 10 April 1961.

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