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Branched-Chain and Other Amino Acids in Tissues of Rats Fed Leucine-Limiting Amino Acid Diets Containing Norleucine^1,2,

Jean K. Tews^*, Joyce J. Repa^*, and Alfred E. Harper^*,

^* Department of Biochemistry Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706

Amino acid concentrations were measured in plasma, brain, muscle and liver from rats fed leucine-limiting diets containing varying proportions of other indispensable amino acids (IAA), the branchedchain amino acids (BCAA) and norleucine, a BCAA analog known to compete with large neutral amino acids (LNAA) for transport into tissues. Leucine was low and other IAA were high when dietary IAA were 125% and leucine was 65% of requirements; higher leucine and lower IAA concentrations occurred when dietary IAA were 75% of requirements. Tissue leucine was high and isoleucine and valine were low in rats fed excess leucine. Norleucine induced dose-dependent reductions in BCAA, especially in brain and muscle in which isoleucine or valine were sometimes undetectable. Leucine was not depressed further when control values were low as in the rats fed 125% IAA. Norleucine frequently prevented the high BCAA found after feeding additional BCAA. Other LNAA tended to be low in the brain and muscle of rats fed norleucine. Lysine was high only in the tissues of rats fed 75% IAA and norleucine; this effect was prevented when added leucine was given. Brain tryptophan, but not always serotonin, was low in rats fed norleucine. The results show transport-related, selective and usually marked depletions of tissue BCAA in rats fed norleucine; this suggests norleucine may be an aid in the treatment of clinical conditions involving excesses of BCAA.

KEY WORDS: • analog • branched-chain amino acids • norleucine • rats • transport

¹ These studies were supported by the College of Agricultural and Life Sciences, by funds from the Research Committee of the Graduate School of the University of Wisconsin-Madison and by grant DK-10747 from the National Institutes of Health, Bethesda, MD.

² Presented in part at the 73rd annual meeting of the Federation of American Societies for Experimental Biology, March 19–23, 1989, New Orleans, LA [Tews, J. K., Repa, J. J. & Harper, A. E. (1989) Food intake, growth, brain amino acids and liver serine dehydratase and GPT activities in rats fed a leucine-limiting diet containing norleucine. FASEB J. 3: A655 (abs. 2491)], and at the First International Congress on Therapy with Amino Acids and Analogues, August 7–12, 1989, Vienna, Austria [Tews, J. K. Feeding behavior, growth and tissue amino acids of rats fed diets containing norleucine or homoarginine].

³ Reprints are not available.

Manuscript received 28 May 1990. Revision accepted 27 August 1990.

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