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Dietary Amino Acid Analogues and Transport of Lysine or Valine across the Blood-Brain Barrier in Rats^1,2,

Departments of Biochemistry and Nutritional Sciences, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI 53706 ^* Department of Neuropathology, Institute of Psychiatry, London SE5 8AF, United Kingdom

Studies were undertaken to determine if dietary disproportions of amino acids would alter flux into brain of the amino acid present in the diet in a growth-limiting concentration. Rats were adapted to a lysine-limiting diet before receiving a meal of this control diet, alone or with added lysine or homoarginine (a competitor for lysine transport) or both, before intravenous infusion of [¹⁴C]lysine. The brain-to-plasma radioactivity ratio was lower in rats fed extra lysine or homoarginine than in rats fed the control diet, whereas lysine flux and brain lysine concentration were high in rats fed extra lysine alone. Flux and concentration were lower in rats fed homoarginine + lysine than in rats fed extra lysine alone. Other rats were fed a valine-limiting diet containing added valine, norleucine (a competitor for valine transport) or both, before [¹⁴C]valine was infused. Valine flux and brain valine concentrations were higher in rats fed extra valine than in control rats, whereas flux was lower in the group fed norleucine alone. Valine flux was higher in rats fed norleucine + valine than in the rats fed norleucine alone. Our studies show that dietary disproportions of amino acids can alter the flux of specific amino acids across the blood-brain barrier.

KEY WORDS: • amino acid analogue • amino acid imbalance • amino acid transport • blood-brain barrier • diet

¹ Supported by National Institutes of Health Grant No. AM-10747 and by funds from Action for the Crippled Child, UK.

² Presented at the Annual Meeting of the Federation of American Societies for Experimental Biology, Washington, DC, March 29–April 3, 1987 [Tews, J. K., Greenwood, J., Pratt, O. E. & Harper, A. E. (1987) Effects of amino acid analogues and imbalance on transport of lysine or valine into brain. Fed. Proc. 46: 892 (abs. 3358)].

Manuscript received 17 June 1987. Revision accepted 26 January 1988.