Our study was undertaken to investigate the in vivo effects of several amino acids on both the uptake of ¹⁴C-l-leucine into the brain and the incorporation of ¹⁴C-l-leucine into the brain protein by using 17-day old rats.
The rats with hyperaminoacidemia, previously produced by intraperitoneal loadings of 0.15 or 0.30 m-moles of a single amino acid twice a day, were intraperitoneally injected with ¹⁴C-leucine, and then, sacrificed one hour following the ¹⁴C-leucine injection.
It was found under the above-mentioned experimental condition, that phenylalanine in excess inhibited not only the uptake of ¹⁴C-leucine into the brain by 50% but also the incorporation of 14C-leucine into brain protein by 48%.
The similar inhibitory effect was observed in case of loading of valine, histidine or methionine, too.
The present results suggest that a few specific amino acids in excess influence both the intracellular accumulation and the incorporation into protein of other amino acids in the brain. It is entirely possible that disturbed transport of amino acids may induce a disruption of the normal balance of free amino acid pools in the brain. The reduction of protein synthesis may partially be accounted for the deficient substances normally present in optimal concentrations in the brain.
Decreased protein synthesis in brain may, in part, explain a cause of neurological dysfunction seen in most of inborn errors of amino acidmetabolism such as PKU.