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The Effect of Valine Deficiency on Neutral Amino Acid Patterns in Plasma and Brain of the Rat¹

Graduate Division of Nutrition, University of Texas, Austin, TX 78712 ^* Department of Pathology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824

Valine deficiency in rats produces motor incoordination attributable to selective damage to the red nuclei, midbrain structures that modulate motor activity. Neither incoordination nor red nuclei damage occurs in rats deprived of valine, isoleucine and leucine, thus suggesting that valine neurotoxicity results from amino acid imbalance rather than from lack of valine per se. To explore this possibility, we compared neutral amino acid patterns in plasma and brain of rats fed for 7 days a complete diet fed ad libitum or pair-fed, a valine-free diet or a diet lacking in all three essential branched-chain amino acids (BCAA). Statistical evaluation showed that plasma valine in valine-deprived rats was lower (P < 0.01) than in pair-fed and ad libitum-fed controls but did not differ from rats lacking BCAA. Brain valine in valine-deprived rats did not differ from ad libitum-fed controls and actually was higher (P < 0.01) than in pair-fed and BCAA-deprived rats. The most striking changes seen in the amino acid pattern of valine-deprived rats as compared to all other groups were in the increased leucine:valine ratio (P < 0.01 for plasma and brain) and in the increased leucine + isoleucine:valine ratio (P < 0.01, plasma; P < 0.001, brain). These results are consistent with the view that amino acid imbalance is a critical factor in the development of the neurotoxicity of valine deficiency.

KEY WORDS: • valine deficiency • amino acid imbalance • amino acids in plasma and brain of valine-deficient rat

¹ Supported by Grant AM-25629 from the National Institutes of Arthritis, Metabolism and Digestive Diseases.

² Present address: Texas Department of Health, 1100 W. 49th Street, Austin, TX 78756.

³ Present address: Texas Air Control Board, 6330 Highway 290 East, Austin, TX 78723.

⁴ Present address: Abbott Laboratories, North Chicago, IL 60064.

⁵ Address reprint requests to: Dr. Betty E. Haskell, 115 Gearing Hall, University of Texas, Austin, TX 78712.

Manuscript received 13 June 1983.