A Defect in the Metabolism of Tyrosine and Phenylalanine in Premature Infants. Ii. Spontaneous Occurrence and Eradication by Vitamin C 12

Abstract

In the preceding paper (1) an account was given of an aberration in the metabolism of tyrosine and phenylalanine in premature infants characterized by the urinary excretion of 1-p-hydroxyphenyllactic and p-hydroxyphenylpyruvic acids. Data on the isolation, identification and properties of these intermediary metabolites and the chemical methods employed for their quantitative assay were presented. Earlier studies (2) had shown an irregular exhibition of the defect in premature infants fed high protein diets and this finding, together with observed variations in the magnitude and duration of excretion of abnormal metabolites in infants receiving equivalent protein intakes, pointed to the importance of other dietary factors besides the level of ingested protein. Later studies (3) demonstrated the curative properties of vitamin C. This paper presents data which establish the following facts: (1) the prevalence and persistence of the defect in premature infants fed high protein diets (5 grams or more per kgm.) devoid of vitamin C; (2) its absence in full term infants receiving similar diets; (3) its production in the latter infants by feeding the pure amino acids, 1-tyrosine or d,1-phenylalanine; (4) the specificity of vitamin C in preventing and eradicating the defect.

Effects of Ascorbic Acid in Alkaptonuria: Alterations in Benzoquinone Acetic Acid and an Ontogenic Effect in Infancy

“…The late development of this enzyme is thought to be the basis of the transient tyrosinemia of the newborn that is particularly common in premature infants. Ascorbic acid is effective in decreasing the levels of tyrosine in such infants (16). The increase in homogentisic acid was interpreted by us to represent a similar activation of p-hydroxyphenylpyruvic acid oxidase in vivo in young infants.…”

The Acid-Base Balance of Premature Infants 1

“…While this study was in progress, work was published on the presence of abnormal products of the metabolism of tyrosine and phenylalanine in the urine of premature infants who had received no ascorbic acid (18,19). All the patients except A53370, A53371, and A53019 had been given 25 mgm.…”

Does Vitamin C Intake Influence the Rate of Tyrosine Catabolism in Premature Babies?

“…Plasma levels achieved at vitamin C intakes of 100 mg/kg/day were not significantly dif ferent from levels achieved at 20 mg/kg/day; kinetic studies in well premature babies have not been conducted, so it is not possible to say whether the results reflect saturation of tissue stores at relatively low doses. The role of vita min C in the catabolism of tyrosine appears to be to overcome substrate inhibition of phydroxyphenyl pyruvate oxidase [1,15]; the potential value of supplementary vitamin C to premature babies is evidently to increase the ascorbic acid/tyrosine ratio in the tissues, rather than to correct a vitamin C deficiency.…”