A Defect in the Metabolism of Tyrosine and Phenylalanine in Premature Infants. I. Identification and Assay of Intermediary Products.

In preceding papers (1, 2), it was shown that premature infants fed vitamin C-free cow's milk mixtures, high in protein (5 grams or more per kgm. per day), exhibit a spontaneous defect in their metabolism of tyrosine and phenylalanine, manifested by the urinary excretion of 1-p-hydroxyphenyllactic and p-hydroxyphenylpyruvic acids. The defect was accentuated by feeding these subjects either amino acid in pure form. Full-term infants fed similar diets did not show the defect spontaneously but it could be induced in them by the ingestion of a single dose (1.0 gram per kgm.) of either amino acid. It was further shown that the administration of 1ascorbic acid in adequate dosage abolished the spontaneous and artificially induced defect in both premature and full-term infants. The presence of this metabolic aberration prompted a more detailed study of the response of infants to repeated oral doses of tyrosine and phenylalanine, with and without dietary vitamin C. In this study, the assays for urinary aromatic organic acids were supplemented by urinary assays for the amino acids themselves. These modified procedures threw further light on the pathways of intermediary aromatic amino acid metabolism and provided evidence of the irreversible conversion of phenylalanine to tyrosine by the living, normal human organism. Perfusion experiments