PHENYLALANINE KINETICS IN SICK PRETERM NEONATES WITH RESPIRATORY-DISTRESS SYNDROME

The cause of hyperphenylalaninemia in sick preterm infants has yet to be determined; one reason may be reduced tolerance to phenylalanine as a consequence of immaturity of phenylalanine hydroxylase. Phenylalani ne metabolism was studied in vivo in 23 ventilated preterm infants of gestational age 23 to 36 wk within the first 6 d of life using a conti nuous i.v. infusion of the stable isotope-labeled amino acids [H-2(5)] phenylalanine, [H-2(4)]tyrosine, and [H-2(2)]tyrosine. Phenylalanine h ydroxylation was calculated from two different methods. In the first m ethod, used in all 23 infants receiving glucose and in seven of these infants who subsequently received parenteral nutrition, phenylalanine hydroxylation was calculated from the plasma enrichments of [H-2(5)]ph enylalanine and [H-2(4)]tyrosine and from the molar ratio of tyrosine to phenylalanine in mammalian tissue protein. In this instance, the me an hydroxylation was 16.0 (SD 10.9) and 48.4 (SD 14.9) mu mol/kg/h, wh ich was 17.3% (SD 8.4%) and 33.2% (SD 9.8%) of the total phenylalanine flux for infants receiving glucose and parenteral nutrition, respecti vely. Additionally, in six infants receiving glucose, hydroxylation wa s calculated from the measured phenylalanine (H-2(5)), independent tyr osine (H-2(2)) fluxes, and the plasma enrichments of (H-2(5)) phenylal anine and its hydroxylation product [H-2(4)]tyrosine. In this case, hy droxylation was 20.5 (SD 13.0) mu mol/kg/h, which represented 22.3% (S D 9.8%) of the phenylalanine flux. In the same six infants, phenylalan ine hydroxylation derived using the first method was 22.2 (SD 13.1) mu mol/kg/h, 23.6% (SD 9.9%) of the total phenylalanine flux. The close agreement between phenylalanine hydroxylation calculated from the enri chment of plasma with [H-2(2)]tyrosine and estimated from the proporti on of phenylalanine to tyrosine in body protein confirms that the inde pendent measurement of tyrosine flux by a constant infusion of [H-2(2) ]tyrosine is not routinely required in the measurement of phenylalanin e hydroxylation in preterm infants. These results do not support the h ypothesis that phenylalanine hydroxylase activity is low in preterm in fants.