Phenylalanine sensitive K562-D cells for the analysis of the biochemical impact of excess amino acid.

[phenylketonuria]

Although it is recognized that the abnormal accumulation of amino acid is a cause of the symptoms in metabolic disease such as phenylketonuria (PKU ), the relationship between disease severity and serum amino acid levels is not well understood due to the lack of experimental model . Here , we present a novel in vitro cellular model using K 562 -D cells that proliferate slowly in the presence of excessive amount of phenylalanine within the clinically observed range , but not phenylpyruvate . The increased expression of the L-type amino acid transporter (LAT 2 ) and its adapter protein 4 F 2 heavy chain appeared to be responsible for the higher sensitivity to phenylalanine in K 562 -D cells . Supplementation with valine over phenylalanine effectively restored cell proliferation , although other amino acids did not improve K 562 -D cell proliferation over phenylalanine . Biochemical analysis revealed mammalian target of rapamycin complex (mTORC ) as a terminal target of phenylalanine in K 562 -D cell proliferation , and supplementation of valine restored mTORC 1 activity . Our results show that K 562 -D cell can be a potent tool for the investigation of PKU at the molecular level and to explore new therapeutic approaches to the disease .

Diseases
Validation

Diseases presenting "abnormal accumulation" symptom

adrenomyeloneuropathy

canavan disease

cutaneous mastocytosis

erdheim-chester disease

gm1 gangliosidosis

phenylketonuria

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