Abstract
Hepatic phenylalanine hydroxylase activity was inhibitied in F344 rat pups by injection with parachlorophenylalanine on days 7, 8, and 9 after birth. On day 10, animals were divided into control and experimental groups. Controls received an injection of phenylalanine, with the characteristic phenylketonuria (PKU) changes of elevated phenylalanine but normal tyrosine levels. The experimental group received a similar injection of phenylalanine but in addition received either a single amino acid or a combination of amino acids from the large neutral amino acids (LNAA) group. The LNAA group of amino acids--phenylalanine, tyrosine, tryptophan, leucine, isoleucine, and valine--compete with each other for entry into brain by a common transport mechanism. Compared with controls, the experimental group had lower phenylalanine levels in brain, but no change in serum levels, giving a lower brain-serum phenylalanine ratio. Increasing the serum concentrations of amino acids competitive with phenylalanine for transport across the blood brain barrier might form an alternative approach to effective dietary treatment of PKU.
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