Effect of phenylalanine on protein synthesis in the developing rat brain

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Abstract
1. Inhibition of the rate of incorporation of [35S]methionine into protein by phenylalanine was more effective in 18-day-old than in 8-day-old or adult rat brain. 2. Among the subcellular fractions incorporation of [35S]methionine into myelin proteins was most inhibited in 18-day-old rat brain. 3. Transport of [35S]methionine and [14C]leucine into the brain acid-soluble pool was significantly decreased in 18-day-old rats by phenylalanine (2mg/g body wt.). The decrease of the two amino acids in the acid-soluble pool equalled the inhibition of their rate of incorporation into the protein. 4. Under identical conditions, entry of [14C]glycine into the brain acid-soluble pool and incorporation into protein and uptake of [14C]acetate into lipid was not affected by phenylalanine. 5. It is proposed that decreased myelin synthesis seen in hyperphenylalaninaemia or phenylketonuria may be due to alteration of the free amino acid pool in the brain during the vulnerable period of brain development. Amyelination may be one of many causes of mental retardation seen in phenylketonuria.