Relationships between phenylalanine hydroxylation and plasma aromatic amino acid concentrations in humans

We investigated the relationships between phenylalanine hydroxylation (Phe Hy) and plasma concentrations of phenylalanine, tyrosine, and glucagon in healthy male volunteers (N = 13; age, 29 +/- 3 years). Phe Hy, as well as the Phe and Tyr rate of appearance (Ra), were measured during L-[2H5]-Phe and L-[2H2]-Tyr continuous intravenous (i.v.) infusions both under basal postabsorptive conditions (N = 13) and following divergent changes of plasma aromatic amino acids (AAA) concentrations. Namely, AAA were increased by administration of a balanced synthetic mixed meal (n = 6) or selectively decreased by i.v. infusion of insulin along with a Phe-deficient, Tyr and tryptophan-deprived amino acid mixture ([IAA] n = 7). Following the meal, plasma Phe (54 +/- 3 to 81 +/- 12 micromol/L), plasma Tyr (54 +/- 4 to 91 +/- 7), Phe Hy (0.09 +/- 0.01 to 0.15 +/- 0.02 micromol/kg x min), Phe Ra (0.65 +/- 0.04 to 0.96 +/- 0.07), and Tyr Ra (0.51 +/- 0.03 to 0.93 +/- 0.11) all significantly increased (P < or = .05 v basal). IAA infusion significantly decreased plasma Phe (to 47 +/- 3 micromol/L), plasma Tyr (to 25 +/- 4), Phe Hy (to 0.07 +/- 0.004 micromol/kg x min), and Tyr Ra (to 0.29 +/- 0.02; all P < or = .05 v sal), while Phe Ra did not change (0.64 +/- 0.04, NS). Plasma glucagon did not change in the three experimental periods (basal, 85 +/- 7; meal, 72 +/- 10; IAA, 92 +/- 14 pg/mL; NS). Using linear regression analysis, plasma Phe was positively related to both Phe Hy (R2 = .76, P < .001) and plasma Tyr (R2 = .80, P < .001); Phe Hy and plasma Tyr were also significantly correlated (R2 = .60, P < .001). No correlation was found between Phe Hy and basal plasma glucagon (R2 = .04, NS). Using multiple regression analysis with plasma Tyr as the dependent variable, plasma Phe was still correlation with plasma Tyr (t = 4.29, P = .0002), while the relationship between Phe Hy and plasma Tyr was no longer significant (t = 0.69, P = .49). These data indicate that plasma Phe is closely associated with its own hydroxylative disposal in humans, and confirm that Phe conversion to Tyr may play a physiological role in maintaining balanced plasma phenylalanine and tyrosine concentrations.