Metabolic conversion of l-[U- 14C]phenylalanine to respiratory 14CO 2 in healthy subjects, phenylketonuria heterozygotes and classic phenylketonurics

Abstract

Ten healthy volunteers, 12 classic phenylketonuria (PKU) heterozygotes, and 5 classic phenylketonurics have been loaded orally with a mixture of 5 μCi of l-[U- 14C]phenylalanine plus 25 mg/kg of l-[ 2H 5]phenylalanine. For 3 h thereafter, carbon-14 activity in expired air and total carbon dioxide were measured continuously and the levels of l-phenylalanine and l-tyrosine in plasma were determined in six blood samples. After 3 h, 15.1 ± 2.1% of the applied dose of radioactivity was recovered in the expired air of the healthy subjects, compared to 10.1 ± 2.2% for PKU heterozygotes and 0.32 ± 0.18% for classic phenylketonurics. The integrated activity expired provides a discrimination between normals and PKU heterozygotes with a classification error of about 13% compared to an error of about 9% based on the fasting l-phenylalanine over l-tyrosine ratio. A combination of these two parameters in a two-dimensional discriminatory analysis reduces the classification error to < 1%. An intraindividual correlation between the absolute activity expired and the formation of l-[ 2H 4]tyrosine formed is shown, confirming that ring hydroxylation of l-phenylalanine to l-tyrosine is mandatory in the catabolism of l-phenylalanine to carbon dioxide.