Effect of α‐Methylphenylalanine and Phenylalanine on Brain Polyribosomes and Protein Synthesis

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Abstract
A chronic hyperphenylalanemia was effectively produced in developing mice by daily administrations of phenylalanine (2 mg/g body wt) and a phenylalanine hydroxylase inhibitor .alpha.-methyl-D,L-phenylalanine (0.43 mg/g body wt). The presence of .alpha.-methylphenylalanine in newborn mice inhibited 65-70% of hepatic phenylalanine hydroxylase activity within 12 h. Since this maximum inhibition persisted for 24 h or longer, decreased enzyme activity was maintained by daily administrations. Whereas concentrations of phenylalanine increased approximately 40-fold in both plasma and brain following injection of .alpha.-methylphenylalanine and phenylalanine, plasma levels of tyrosine were not altered significantly. Concomitant with changes in phenylalanine concentrations the brain polyribosomes'' disaggregation, which reached a maximum 3 h after infection and persisted as long as 18 h, was observed. Polyribosomes did not become refractory to as many as 10 daily injections of .alpha.-methylphenylalanine and phenylalanine. In addition to polyribosome disaggregation, chronic hyperphenylalanemia reduced the rates of polypeptide chain elongation on polyribosomes isolated from brain homogenates.