Metabolic Derangements in Response of Rats to Ingestion of Imbalanced Amino Acid Mixtures

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Abstract
Histidine-U-14C and threonine-U-14C were used in tracer quantities to compare the effect of histidine imbalance on their metabolic behavior. Three groups of rats (six rats per group) were fed basal, histidine-imbalanced, and corrected diets. Two rats from each group were killed 2, 4 and 6 hours after feeding each diet. Radioactivity was determined in expired CO2, urine and feces as well as in protein and nonprotein fractions of rat tissues. The experiment was done twice, once with histidine-U-14C, and once with threonine-U-14C to permit comparison between the behavior of limiting and nonlimiting amino acids in the imbalanced diet groups and their respective control groups (basal and corrected). Radioactivity losses from histidine in expired CO2, urine and feces, and its incorporation into lipid fractions were lower in rats fed the imbalanced diet. The corresponding losses and incorporation values for threonine were higher. After 6 hours, radioactivity values in the TCA-soluble fractions of the tissues of rats fed the imbalanced diet containing labeled histidine were significantly lower than those of the control groups; in the protein fractions the reverse was true. Nonlimiting threonine behaved in an opposite manner. Radioactivity in both histidine and threonine isolated from hydrolyzed liver protein of the imbalanced diet groups was increased. However, significant differences in retention efficiency and efficiency of utilization of these amino acids were demonstrated; both parameters were higher for histidine and lower for threonine in the imbalanced diet groups. These results indicate enhanced protein synthesis, and validate Harper's hypothesis (1, 2) that the limiting amino acid is utilized with higher efficiency in protein synthesis subsequent to ingesting imbalanced amino acid mixtures.