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Induction of Threonine Imbalance by Dispensable Amino Acids: Relationships Between Tissue Amino Acids and Diet in Rats¹

Departments of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706

The ability of low-protein diets supplemented with small neutral, dispensable amino acids to induce changes in tissue threonine concentrations characteristic of threonine imbalance was examined. Brain threonine concentrations were usually decreased when rats were fed threonine-limiting diets supplemented with small neutral amino acids which compete with threonine for transport into brain slices in vitro (serine, alanine or -amino-n-butyrate). The decreases were related inversely to increased plasma levels of the small neutral amino acids. Threonine concentrations in liver and muscle were not significantly decreased. Threonine levels in plasmas from control rats were so low that further diet-induced decreases did not always occur; however, large decreases occurred in both plasma and brain of rats fed diets supplemented with 0.1% threonine plus mixtures of either small neutral or indispensable amino acids. Dietary supplements of amino acids not inhibitory of threonine transport (aspartate, glutamate, proline or GABA) did not induce changes in brain or plasma threonine concentrations and, except for proline, did not increase concentrations of the respective amino acid in brain. These results support the hypothesis that induction of amino acid imbalances may involve competition by specific plasma amino acids for transport into the brain of an indispensable, limiting amino acid such as threonine.

KEY WORDS: • amino acid transport • amino acid imbalance • brain • lysine • threonine • tissue amino acids • rats

¹ Supported in part by the College of Agricultural and Life Sciences, University of Wisconsin, Madison, and by Grant AM 10747 from the National Institutes of Health, Bethesda, MD.

Manuscript received 30 July 1979.