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

Authors


  • This study was supported by grant BNS 05826 from the National Science Foundation and by the Kansas Agricultural Experiment Station. This is contribution 81-57-j, Division of Biology, the Kansas Agricultural Experiment Station, Kansas State University.

Address correspondence and reprint requests to Dr. Terry C. Johnson.

Abstract

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 α-methyl-D, L-phenylalanine (0.43 mg/g body wt). The presence of α-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 α-methylphenylalanine and phenylalanine, plasma levels of tyrosine were not altered significantly. Concomitant with changes in phenylalanine concentrations we observed the brain polyribosomes' disaggregation, which reached a maximum 3 h after injection and persisted as long as 18 h. Polyribosomes did not become refractory to as many as 10 daily injections of α-methylphenylalanine and phenylalanine. In addition to polyribosome disaggregation, chronic hyperphenylalanemia reduced the rates of polypeptide chain elongation on polyribosomes isolated from brain homogenates.

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