Experimentally induced and natural recovery from the effects of phenylalanine on brain protein synthesis.

ABSTRACT

The decrease in the neural polyribosomes produced during hyperphenylalaninemia could not be restored to normal levels by the injection of other single neutral amino acids. All of the neutral amino acids that are transported with phenylalanine were found to produce an alteration of neural polyribosomes similar to that measured with phenylalanine. However, the injection of a balanced mixture of 6 or 7 neutral amino acids could restore the brain polyribosomes to normal states. Although this experimentally induced recovery did not lower brain phenylalanine concentrations, it did restore the acylation levels of methionyl-tRNA, and in particular, the methionyl-tRNA initiator species. This also led to a concomitant stimulation of the elongation rate of brain polypeptide synthesis. A natural recovery of brain polyribosomal levels (occurring 2 h after 1 mg/g phenylalanine is injected) did not appear to represent a real recovery of neural protein metabolism. Phenylalanine concentrations were increased in the brain, the acylation levels of methionyl-tRNA, alanyl-tRNA and the initiator methionyl-tRNA remained altered, and the rate of ribosome translocation was decreased 28%.