Metabolic conversion of L-[U-14C]phenylalanine to respiratory 14CO2 in healthy subjects, phenylketonuria heterozygotes and classic phenylketonurics.
Ten healthy volunteers, 12 classic phenylketonuria (PKU) heterozygotes, and 5 classic phenylketonurics have been loaded orally with a mixture of 5 microCi of L-[U-14C]phenylalanine plus 25 mg/kg of L-[2H5]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 less than 1%. An intraindividual correlation between the absolute activity expired and the formation of L-[2H4]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.
D001944:Breath Tests; D002245:Carbon Dioxide / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003903:Deuterium; D006579:Heterozygote; D006801:Humans; D006900:Hydroxylation; D010649:Phenylalanine / Q000378:metabolism*; D010661:Phenylketonurias / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D002250:Carbon Radioisotopes; D002245:Carbon Dioxide; D014443:Tyrosine; D010649:Phenylalanine; D003903:Deuterium