Tyrosine requirements in children with classical PKU determined by indicator amino acid oxidation

Abstract

Tyrosine (Tyr) is an essential amino acid in phenylketonuria (PKU) because of the limited hydroxylation of phenylalanine (Phe) to Tyr. The recommended intakes for Tyr in PKU are at least five times the recommended phenylalanine intakes. This suggests that Phe and Tyr contribute ∼20 and 80%, respectively, of the aromatic amino acid (AAA) requirement (REQ). In animals and normal humans, dietary Tyr was shown to spare 40–50% of the Phe requirement, proportions that reflect dietary and tissue protein composition. We tested the hypothesis that the Tyr REQ in PKU would account for 45% of the total AAA REQ by indicator amino acid oxidation (IAAO). Tyr REQ was determined in five children with PKU by examining the effect of varying dietary Tyr intake on lysine oxidation and the appearance of 13CO2 in breath (F13CO2) under dietary conditions of adequate energy, protein (1.5 g ⋅ kg− 1 ⋅ day− 1), and phenylalanine (25 mg ⋅ kg− 1 ⋅ day− 1). Lysine oxidation and F13CO2 were determined using a primed 4-h oral equal-dose infusion ofl-[1-13C]lysine. Lysine oxidation and F13CO2 decreased linearly as Tyr intake increased, to a break point that was interpreted as the mean dietary Tyr requirement (16.3 and 19.2 mg ⋅ kg− 1 ⋅ day− 1, respectively). At Tyr intakes of >16.3 and 19.2 mg ⋅ kg− 1 ⋅ day− 1, lysine oxidation and F13CO2, respectively, were low and constant. This represents 40.4 and 44.4%, respectively, of the total AAA intake. The current recommendations for Tyr intake in PKU patients appear to be overestimated by a factor of ∼5. This study is the first application of the IAAO technique in a pediatric population and in humans with an inborn error of metabolism.