Decreases in brain protein synthesis elicited by moderate increases in plasma phenylalanine

Large increases in plasma phenylalanine concentration (greater than 1 mM) adversely affect brain function and inhibit cerebral protein synthesis. The threshold hypothesis predicts that moderate increases in plasma phenylalanine concentrations below a 1 mM threshold have no adverse effects on brain function or protein synthesis. Using a new in situ internal carotid artery perfusion technique and measurement of the amino acyl-tRNA specific activities by high performance liquid chromatography (HPLC) separation of phenylisothiocyanate (PITC) derivatized amino acids, the present studies demonstrate a linear decrease in cerebral protein synthesis in vivo in proportion to moderate increases in plasma phenylalanine. A 50% inhibition of brain protein synthesis in vivo is observed at a plasma phenylalanine concentration of approximately 0.40 mM. Since moderate increases in plasma phenylalanine concentrations may be achieved in humans with ingestion of phenylalanine, the present findings should be considered in evaluating the safety of liberal and selective increases in dietary phenylalanine.