Effect of alpha-methylphenylalanine and phenylalanine on brain polyribosomes and protein synthesis.
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 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 alpha-methylphenylalanine and phenylalanine. In addition to polyribosome disaggregation, chronic hyperphenylalanemia reduced the rates of polypeptide chain elongation on polyribosomes isolated from brain homogenates.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D010441:Peptide Chain Elongation, Translational; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D009419:Nerve Tissue Proteins; D014443:Tyrosine; C012436:alpha-methylphenylalanine; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase