| Abstract: | Valine deficiency in rats produced 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 less than 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 less than 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 less than 0.01 for plasma and brain) and in the increased leucine + isoleucine:valine ratio (P less than 0.01 plasma; P less than 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. |
