SLC2A1 tetramer does not transport Glc from extracellular region to cytosol

Stable Identifier
R-HSA-5632804
Type
Reaction [transition]
Species
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
19798636 Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1

Suls, A, Mullen, SA, Weber, YG, Verhaert, K, Ceulemans, B, Guerrini, R, Wuttke, TV, Salvo-Vargas, A, Deprez, L, Claes, LR, Jordanova, A, Berkovic, SF, Lerche, H, De Jonghe, P, Scheffer, IE

Ann. Neurol. 2009
9462754 GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier

Seidner, G, Alvarez, MG, Yeh, JI, O'Driscoll, KR, Klepper, J, Stump, TS, Wang, D, Spinner, NB, Birnbaum, MJ, De Vivo, DC

Nat. Genet. 1998
20687207 Glut1 deficiency: inheritance pattern determined by haploinsufficiency

Rotstein, M, Engelstad, K, Yang, H, Wang, D, Levy, B, Chung, WK, De Vivo, DC

Ann. Neurol. 2010
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
D-glucose transmembrane transporter activity of SLC2A1 mutants [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
infantile epileptic encephalopathy 2481 infantile spasm
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