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Tyrosine requirements in children with classical PKU determined by indicator amino acid oxidation
R Bross1, R O Ball, J T Clarke
1Department of Nutritional Sciences, University of Toronto, Toronto, Ontario M5S 3E2.
Insights
Tyrosine is essential for phenylketonuria (PKU) patients. This study found current tyrosine intake recommendations for PKU are overestimated, suggesting lower requirements for managing this metabolic disorder.
Area of Science:
- Biochemistry
- Nutritional Science
- Metabolic Disorders
Background:
- Tyrosine (Tyr) is essential in phenylketonuria (PKU) due to impaired phenylalanine (Phe) hydroxylation.
- Current PKU guidelines suggest high Tyr intake, potentially 80% of aromatic amino acid (AAA) needs.
Purpose of the Study:
- To determine the true tyrosine requirement in children with PKU using the indicator amino acid oxidation (IAAO) method.
- To test the hypothesis that Tyr accounts for 45% of the total AAA requirement in PKU.
Main Methods:
- Employed the IAAO technique with L-[1-(13)C]lysine infusion in five children with PKU.
- Monitored lysine oxidation and breath (13)CO(2) (F(13)CO(2)) at varying dietary Tyr intakes.
Main Results:
- Lysine oxidation and F(13)CO(2) decreased linearly with increasing Tyr intake, indicating a Tyr requirement breakpoint.
- The determined mean dietary Tyr requirement was 16.3-19.2 mg/kg/day, representing 40.4-44.4% of total AAA intake.
- This suggests current Tyr recommendations for PKU may be overestimated by approximately fivefold.
Conclusions:
- The IAAO method successfully determined Tyr requirements in pediatric PKU.
- Findings indicate a lower Tyr requirement in PKU than currently recommended.
- This study provides crucial data for refining nutritional management in PKU.
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 approximately 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 (13)CO(2) in breath (F(13)CO(2)) under dietary conditions of adequate energy, protein (1.5 g x kg(-1) x day(-1)), and phenylalanine (25 mg x kg(-1) x day(-1)). Lysine oxidation and F(13)CO(2) were determined using a primed 4-h oral equal-dose infusion of L-[1-(13)C]lysine. Lysine oxidation and F(13)CO(2) 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 x kg(-1) x day(-1), respectively). At Tyr intakes of >16.3 and 19.2 mg x kg(-1) x day(-1), lysine oxidation and F(13)CO(2), 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 approximately 5. This study is the first application of the IAAO technique in a pediatric population and in humans with an inborn error of metabolism.