Meta-Biol

• Pathways

Members of the SLC2A family encode glucose transporter (GLUT) proteins that mediate the facilitated diffusion of glucose between the extracellular space and the cytosol. While the monomeric protein can form a channel and transport glucose, kinetic studies suggest that the functional form of the protein is a homotetramer. SLC2A1 (GLUT1) is expressed by many cell types, notably endothelial cells, red blood cells and cells of the brain. Its low Km for glucose (~1 mM) relative to normal blood glucose concentration (~5 mM) allows these cells to take up glucose independent of changes in blood glucose levels. Defects in SLC2A1 can cause neurological disorders with wide phenotypic variability. The most severe 'classic' phenotype, GLUT1 deficiency syndrome 1 (GLUT1DS1; MIM:606777), comprises infantile-onset epileptic encephalopathy associated with delayed development, acquired microcephaly, motor incoordination and spasticity. A residual enzyme activity between 25-50% in mutations is the cause of the severe 'classic' phenotype. Mutations having this residual activity include R126L, K256V, K456*, Y449*, S342L, R223P and R126C (Rotstein et al. 2010, Seidner et al. 1998, Suls et al. 2009).