Developmental changes of cerebral phenylalanine uptake from severely elevated blood levels.

Brain phenylalanine concentrations at plasma levels raised to that in phenylketonuric subjects were studied in rats from fetal through postnatal life. Suppression of the hepatic phenylalanine hydroxylase with alpha methylphenylalanine, and injections of age-adjusted doses of phenylalanine on the next day, assured the persistence of the same elevation of plasma levels for at least four hours prior to assay. The net phenylalanine uptake determined under these conditions underwent several-fold decreases between the fourth day and the end of the suckling period, and by about the age of 30 days it was as low as in adulthood. The development of transport properties studied here could contribute to the change with age in the vulnerability of the brain to the same degree of hyperphenylalaninemia and, since the cerebral phenylalanine uptake may decrease to non-damaging levels during childhood, it is pertinent to defining the age at which the rigorous diet of phenylketonurics might be safely relaxed.