Abstract
Extract: The effects of excess phenylalanine and deprivation of this amino acid on brain weight, ribonucleic acid (RNA), deoxyribonucleic acid (DNA), protein, and amino acid composition have been studied in the young rat.
Six-week-old male rats were fed for 2 weeks solid diets containing 0.26 g/100 ml phenylalanine (Phe controls), 7 g/100 ml phenylalanine (high Phe), and 0.06 g/100 ml phenylalanine (low Phe). Total brain RNA of rats fed the 7-g diet was 2.41 ± 0.14 mg (mean ± SE), and total brain protein was 124.24 ± 6.34 mg (mean ± SE). Total brain RNA of controls was 3.62 ± 0.17 mg (mean ± SE), and total brain protein was 187.51 ± 3.73 mg (mean ± SE). The brains of rats fed the 7-g diet contained significantly less (P < 0.01) RNA and protein when compared with controls; DNA was not significantly changed. There was no significant diminution of the DNA, RNA, and protein content of brain in rats fed low amounts of Phe.
High levels of phenylalanine found in animals mainted for 2 weels on the high phenylalanine diet were associated with increased amounts of phenylalanine and tyrosine and decreased amounts of valine, serine, threonine, methionine, isoleucine, and leucine in the brain. Low levels of phenylalanine found in animals fed low phenylalanine diets for 2 weeks were associated only with an increase in glycine content of the brain.
Speculation: The mechanisms of mental retardatin associated with some inborn errors of amino acid metabolism are unknown. High levels of phenylalanine in blodd coupled with altered amino acid composition of the brain may interfere with the mechanisms for synthesis of protein and RNA. It would seem appropriate to speculate that, since DNA levels remains constant in developed rat brain exposed to high phenylalanine diets, the derangement in the amino acid pool has an inhibitory effect on protein and RNA synthesis at the cytoplasmatic level. Altered brain protein and RNA synthesis may be of importance not only to central nervous system development in the neonatal period, but also to function in older phenylketonuric children.
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Castells, S., Zischka, R. & Addo, N. Alteration in Composition of Deoxyribonucleic Acid, Ribonucleic Acid, Proteins, and Amino Acids in Brain of Rats Fed High and Low Phenylalanine Diets. Pediatr Res 5, 329–334 (1971). https://doi.org/10.1203/00006450-197107000-00005
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DOI: https://doi.org/10.1203/00006450-197107000-00005
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