Effect of Amino Acid Imbalance on the Fate of the Limiting Amino Acid

Abstract

The fate of the most limiting amino acid (i.e., tracer quantities of threonine-U-¹⁴C or histidine-U-¹⁴C) was studied in rats fed a single meal of a low protein diet in which an amino acid imbalance had been created by the addition of an amino acid mixture devoid of threonine or histidine. The amino acid imbalances did not increase the rate of oxidation of labeled amino acids as indicated by measurement of radioactivity in expired carbon dioxide; they did not result in enhanced excretion of radioactivity in urine or feces; nor did they result in enhanced incorporation of radioactivity into liver glycogen or fat. The accumulated evidence indicated that amino acid incorporation into liver proteins was enhanced by the amino acid imbalances. Incorporation into other tissue proteins was not depressed, and total retention of label in carcass was slightly greater as a result of the imbalance. On the basis of these and other observations, a hypothesis was formulated to explain the effects of amino acid imbalances. It is suggested that an imbalance leads to more efficient incorporation of the growth-limiting amino acid into tissues with the result that its concentration in blood plasma decreases within a few hours after ingestion of the imbalanced meal. This phenomenon, which resembles the response of an animal to a severely deficient diet — a protective response — results in a signal to an appetite-regulating center indicating that the diet is much more deficient than it actually is. Food intake is subsequently depressed and the food intake depression results in retarded growth.