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Effect of α‐Methylphenylalanine and Phenylalanine on Brain Polyribosomes and Protein Synthesis
Author(s) -
Binek Patricia A,
Johnson Terry C,
Kelly Chester J
Publication year - 1981
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1981.tb00589.x
Subject(s) - phenylalanine , hyperphenylalaninemia , polysome , phenylalanine hydroxylase , tyrosine , endocrinology , tyrosine hydroxylase , medicine , chemistry , biochemistry , enzyme , biology , amino acid , rna , ribosome , gene
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.