Phenylalanine hydoxylase in human liver during development.

Abstract

Extract: Phenylalanine hydroxylase activity is present in the liver of human fetuses after the 8th week of gestation, and activities similar to those found in liver from adult control subjects are reached at around the 13th fetal week. The mean enzyme activity in fetal liver after the 13th week of gestation was 107 μmoles tyrosine formed per g protein per hr, and 130 μumoles in livers from adult control subjects. In premature infants soon after birth the mean enzyme activity was 67 μmoles tyrosine formed. This difference from the level of activity in fetuses could be due to loss of activity during the 1–3-hr delay in obtaining liver samples after death. When the pteridine cofactor was omitted from the enzyme assay system only very low activity was found in the livers of fetuses which were studied. Tyrosine was formed when isolated fetal livers were perfused with phenylalanine. The Km for phenylalanine hydroxylase from the liver of human fetuses was 9 × 10-4 m and for liver from adults was 1 × 10-3 m. Thus, the human fetus and immature newborn infant do not lack phenylalanine hydroxylase in the liver. Speculation: The human fetus and immature newborn infant have considerable phenylalanine hydroxylase activity in the liver. The hyperphenylalaninemia or reduced tolerance for phenylalanine found in some infants with low birth weight should thus, not be paralleled with a transient form of phenylketonuria, but could rather be caused by a reduced efficiency of some other component of the phenylalanine-hydroxylating system.