title: Human LAT1 single nucleotide polymorphism N230K does not alter phenylalanine transport.
abstract: The deleterious effects on the brain of phenylketonuria are caused by the saturation of the blood-brain barrier large neutral amino acid transporter type 1 (LAT1) by high plasma phenylalanine concentrations. There is only one known single nucleotide polymorphism (SNP) of the open reading frame of human LAT1, N230K. Site-directed mutagenesis of the wild type human LAT1 cDNA replicated the N230K SNP, and the corresponding cloned RNA encoding either the wild type or N230K human LAT1 were injected into frog oocytes. The kinetics of phenylalanine transport via either form of the human LAT1 was not significantly different. Similarly, there was no difference in the kinetics of phenylalanine transport via the wild type rabbit LAT1 or the corresponding K226N mutant of rabbit LAT1. These studies demonstrate that the only known SNP in the open reading frame of human LAT1 has no effect on the kinetics of large neutral amino acid transport via this carrier.
authors.affiliation: Department of Medicine, UCLA, Los Angeles, CA 90024, USA. rboado@mednet.ucla.edu
authors.forename: Ruben J
authors.initials: RJ
authors.lastname: Boado
authors.forename: Jian Yi
authors.initials: JY
authors.lastname: Li
authors.forename: Petra
authors.initials: P
authors.lastname: Wise
authors.forename: William M
authors.initials: WM
authors.lastname: Pardridge
mesh_terms: D000818:Animals; D001001:Anura; D001216:Asparagine / Q000235:genetics; D001692:Biological Transport; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000378:metabolism; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics*; D008239:Lysine / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011817:Rabbits
chemical_list: D027283:Large Neutral Amino Acid-Transporter 1; D010649:Phenylalanine; D001216:Asparagine; D008239:Lysine