THE EFFECT OF ELEVATED PLASMA PHENYLALANINE LEVELS ON PROTEIN-SYNTHESIS RATES IN ADULT-RAT BRAIN

Increasing the plasma phenylalanine concentration to levels as high as 0.560-0.870 mM (over ten times normal levels) had no detectable effect on the rate of brain protein synthesis in adult rats. The average rates for 7-week-old rats were: valine, 0.58+/-0.05%/h, phenylalanine, 0.59+/-0.06%/h, and tyrosine, 0.60+/-0.09%/h, or 0.59+/-0.06%/h overall. Synthesis rates calculated on the basis of the specific activity of the tRNA-bound amino acid were slightly lower (4% lower for phenylalanine) than those based on the brain free amino acid pool. Similarly, the specific activities of valine and phenylalanine in microdialysis fluid from striatum were practically the same as those in the brain free amino acid pool. Thus the specific activities of the valine and phenylalanine brain free pools are good measures of the precursor specific activity for protein synthesis. In any event, synthesis rates, whether based on the specific activities of the amino acids in the brain free pool or those bound to tRNA, were unaffected by elevated levels of plasma phenylalanine. Brain protein synthesis rates measured after the administration of quite large doses of phenylalanine (> 1.5 mu mol/g) or valine (15 mu mol/g) were in agreement (0.62+/-0.01 and 0.65+/-0.01%/h respectively) with the rates determined with infusions of trace amounts of amino acids. Thus the technique of stabilizing precursor-specific activity, and pushing values in the brain dose to those of the plasma, by the administration of large quantities of precursor, appears to be valid.