Possible Interaction: Phenylalanine and Tryptophan

“Furthermore, Krause et al. (4) reported an inverse relationship between NA and DA plasma concentrations and Phe because high Phe concentrations decrease the availability of the amino acids Tyr and Trp , the precursors of catecholamines and serotonin [5-hydroxytryptamine (5HT)], respectively (5)(6)(7).”

“Quantification of cellular uptake reveals that substitution of Trp by Phe strongly reduces the internalization of all peptides despite the fact that they strongly accumulate in the cell membrane.”

“Using PAHenu2 mice (ENU2), the genetic mouse … PKU, we previously demonstrated that high phenylalanine levels … brain tryptophan hydroxylase activity by reducing the availability of serotonin (5-hydroxytryptamine, 5-HT), crucial for maturation of … in the prefrontal cortex (PFC), around the third postnatal week, a critical period for cortical maturation.”

“ Phenylalanine at similar concentrations to those found in phenylketonuric patients competitively inhibits tryptophan uptake, with aKi of the same order as theKm for tryptophan.”

“The Trp and Phe constitute critical amino acids in this interaction.”

“In the control subjects the rate of absorption of phenylalanine from phenylalanyl-phenylalanine and of tryptophan from glycyl-tryptophan was slower than after the equivalent amount of the free amino acids.”

“As demonstrated on several peptides, aromatic amino acid residues Trp, Tyr, Phe and His are targeted with high selectivity to Trp.”

“ TRP and LEU decreased intake more than PHE (reductions relative to control, ~219 ± 68, ~170 ± 48 and ~12 ± 57 kcal, respectively), and TRP decreased intake more than GLN (~31 ± 82 kcal).”

“In contrast, the substitution of Phe by Trp had an unfavorable effect on the antimicrobial activity.”

“In addition, significant inhibition of the apical-tobasolateral permeation of Trp by Leu and Phe was observed.”