HEPATIC METABOLISM OF PHENYLALANINE DURING DEVELOPMENT*

Abstract

Liver preparations from fetal rats, rabbits, pigs and a human premature infant were essentially incapable of forming tyrosine from phenylalanine. Supplementation with adult rat liver fractions indicated that each was deficient in the specific component of the phenylalanine hydroxylase system. The activity of fetal rat liver was not affected by addition of 2-amino-4-hydroxy-6,7-dimethyltetrahydro-pteridine, which is active as a cofactor in the hydroxylase enzyme. Phenylpyruvate underwent transamination with several amino donors in the mitochondrial and soluble fractions of rat liver; glutamate and glutamine were particularly effective. In mitochondria, reaction with glutamine went to completion, while reaction with glutamate approached equilibrium. Assay of phenylpyruvate-glutamate tramsamination in the livers of fetal and neonatal rats indicated that activity is present during late fetal life, reached the adult level by birth, and was higher than that of the adult during the neonatal period. Differences in the developmental patterns of phenylalanine hydroxylation and transamination are discussed from the point of view of substrate control.