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Effects of Branched-chain Amino Acid Antagonism in the Rat on Tissue Amino Acid and Keto Acid Concentrations¹

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

Growth rate, plasma amino acid, and -keto acid concentrations and activities of the branched-chain amino acid degradative enzymes of rats were measured. Effects of ingestion of excessive amounts of branched-chain amino acids on these variables were determined. Excessive intake of a single branched-chain amino acid led rapidly to elevated plasma concentration of both the amino acid administered and its corresponding -keto acid and, if the rats had previously been fed a low protein diet, to an increase in liver branched-chain -keto acid dehydrogenase activity. Only leucine caused, in addition, marked growth and food intake depression and decreased plasma isoleucine, valine, -keto-ß-methylvaleric acid and -keto isovaleric acid concentrations. The growth depression was associated with food intake depression and could be moderated by addition of isoleucine and valine to the diet. The decreases in plasma isoleucine, valine, -keto-ß-methylvaleric acid and -keto isovaleric acid were not caused by increased degradation of these metabolites to carbon dioxide as branched-chain amino acid oxidation rates in vivo were unchanged by leucine loading and the degradative enzymes were unchanged in adequately fed rats. The decreased concentrations of these amino and keto acids may be the result of decreased protein degradation or increased protein synthesis, possibly mediated by insulin.

KEY WORDS: • branched-chain amino acid • branched-chain keto acid • antagonism • dehydrogenase

¹ Supported in part by the College of Agricultural and Life Sciences, University of Wisconsin-Madison and by grant No. AM 10748 from the U.S. Public Health Service, National Institutes of Health.

² Present address: Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706.

Manuscript received 4 October 1976.