Effects of dietary mixtures of amino acids on fetal growth and maternal and fetal amino acid pools in experimental maternal phenylketonuria

Background: Branched-chain amino acids have been reported to improve fetal brain development in a rat model in which maternal phenylketonuria (PKU) is induced by the inclusion of an inhibitor of phenylalanine hydroxylase, DL- p-chlorophenylalanine, and L-phenylalanine in the diet. Objective: We studied whether a dietary mixture of several large neutral am ino acids (LNAAs) would improve fetal brain growth and normalize the fetal brain amino acid profile in a rat model of maternal PKU induced by DL-alpha -methylphenylalanine (AMPhe). Design: Long-Evans rats were fed a basal diet or a similar diet containing 0.5% AMPhe + 3.0% L-phenylalanine (AMPhe + Phe diet) from day 11 until day 20 of gestation in experiments to test various mixtures of LNAAs. Maternal weight gains and food intakes to day 20, fetal body and brain weights at da y 20, and fetal brain and fetal and maternal plasma amino acid concentratio ns at day 20 were measured. Results: Concentrations of phenylalanine and tyrosine in fetal brain and in maternal and fetal plasma were higher and fetal brain weights were lower i n rats fed the AMPhe + Phe diet than in rats fed the basal diet. However, f etal brain growth was higher and concentrations of phenylalanine and tyrosi ne in fetal brain and in maternal and fetal plasma were lower in rats fed t he AMPhe + Phe diet plus LNAAs than in rats fed the diet containing AMPhe Phe alone. Conclusion: LNAA supplementation of the diet improved fetal amino acid prof iles and alleviated most, but not all, of the depression in fetal brain gro wth observed in this model of maternal PKU.