Functional consequences of an in vivo mutation in exon 10 of the human GLUT1 gene

FEBS Letters

Keller, Konrad¹  Lange, Peter¹  Gertsen, Elena²  Monden, Ingrid¹  Klepper, Jörg² 

[1] Institute of Pharmacology, Freie Universität Berlin, Thielallee 67–73, D-14195 Berlin, Germany;Department of Pediatrics and Pediatric Neurology, University of Essen, Hufelandstr. 55, D-45122 Essen, Germany

关键词: Facilitated glucose transporter isoform 1;    Facilitated glucose transporter isoform 1 deficiency syndrome;    Transport kinetics;    Xenopus oocyte;    2-DOG;    2-deoxy-D-glucose;    GLUT1;    facilitated glucose transporter isoform 1;    GLUT1-DS;    Glut1 deficiency syndrome;    3-OMG;    3-O-methyl-D-glucose;   

DOI  :  10.1016/S0014-5793(03)01247-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The functional consequences of an in vivo heterozygous insertion mutation in the human facilitated glucose transporter isoform 1 (GLUT1) gene were investigated. The resulting frameshift in exon 10 changed the primary structure of the C-terminus from 42 in native GLUT1 to 61 amino acid residues in the mutant. Kinetic studies on a patient's erythrocytes were substantiated by expressing the mutant cDNA in Xenopus laevis oocytes. K _m and V _max values were clearly decreased explaining pathogenicity. Targeting to the plasma membrane was comparable between mutant and wild-type GLUT1. Transport inhibition by cytochalasin B was more effective in the mutant than in the wild-type transporter. The substrate specificity of GLUT1 remained unchanged.

【 授权许可】

Unknown