Phenylketonuria (PKU) is a
genetic disorder caused by deficiency of
phenylalanine hydroxylase (PAH) that requires life-long adherence to a low-
phenylalanine (Phe) diet.
Glycomacropeptide (GMP) is uniquely suited to the nutritional management of PKU, because pure GMP contains no Phe. Our aim was to assess how ingestion of diets containing GMP support growth and affect the concentrations of
amino acids in plasma and brains of mice with a deficiency of PAH, the Pah(enu2) mouse (PKU mouse). Experiments were conducted in 4- to 6-wk-old wild-type (WT) (C57Bl/6) and PKU mice fed diets containing 20%
protein from
casein,
amino acids, or GMP supplemented with limiting indispensable
amino acids (IAA). PKU mice fed the GMP diet showed gains in
body weight, feed efficiency, and a
protein efficiency ratio that did not differ from the
amino acid diet. The concentrations of
isoleucine and
threonine in plasma showed a significant 2- to 3-fold increase for WT and PKU mice fed GMP compared with
casein or
amino acid diets, respectively. PKU mice fed the GMP diet had decreased concentrations of Phe in plasma (11% decrease) and in 5 regions of the brain (20% decrease) compared with the
amino acid diet. The concentration of Phe in the brain was inversely correlated with the concentrations of
isoleucine,
threonine, and
valine in plasma (R2 = 0.74; P < 0.0001), suggesting competitive inhibition of Phe transport into the brain. In summary, PKU mice fed GMP showed comparable growth and reduced concentrations of Phe in plasma and the brain compared with an
amino acid diet. These data support the use of GMP supplemented with IAA as an alternative source of
dietary protein for individuals with PKU.