Practice question

GLUT1 encoded by SLC2A1 on 1p34 is prototype basal transporter responsible for constitutive glucose uptake in erythrocytes where it comprises about five percent of membrane protein, endothelial cells of blood-brain and retinal barriers, astrocytes and fetal tissues requiring continuous supply. It functions as twelve transmembrane uniporter via alternating access low Km 1-2 mM ensuring efficient transport even at low plasma glucose near three millimolar during fasting delivering substrate for glycolysis and pentose phosphate producing NADPH. Genetic haploinsufficiency from heterozygous missense or nonsense mutations causes GLUT1 deficiency syndrome De Vivo disease autosomal dominant characterized by infantile refractory seizures starting early, acquired microcephaly, developmental delay, ataxia and hypoglycorrhachia with cerebrospinal fluid glucose below 3.3 mM while blood normal. In patient cells glucose uptake declines markedly in 2-deoxyglucose assay forcing reliance on ketone bodies and lactate alternative fuels for brain. Compensation by GLUT4 limited because expression restricted to insulin-responsive muscle and adipose not cerebrovascular endothelium and cannot be upregulated. Ketogenic diet producing beta-hydroxybutyrate crossing via MCT1 benefits by bypassing defect restoring energy and reducing seizures.