Human LAT1 single nucleotide polymorphism N230K does not alter phenylalanine transport

The deleterious effects on the brain of phenylketonuria are caused by the saturation of the blood-brain barrier large neutral amino acid transporter type I (LATI) by high plasma phenylalanine concentrations. There is only one known single nucleotide polymorphism (SNP) of the open reading frame of human LATI, N230K. Site-directed mutagenesis of the wild type human LATI cDNA replicated the N230K SNP, and the corresponding cloned RNA encoding either the wild type or N230K human LATI were injected into frog oocytes. The kinetics of phenylalanine transport via either form of the human LATI was not significantly different. Similarly, there was no difference in the kinetics of phenylalanine transport via the wild type rabbit LATI or the corresponding K226N mutant of rabbit LATI. These studies demonstrate that the only known SNP in the open reading frame of human LATI has no effect on the kinetics of large neutral amino acid transport via this carrier. (C) 2004 Elsevier Inc. All rights reserved.