2.A.1.1.28
The erythrocyte/brain hexose facilitator, glucose transporter-1, Gtr1. SLC2a1 or Glut1. Transports D-glucose, dehydroascorbate, arsenite and the flavonone, quercetin, via one pathway and water via a distinct channel. Sugar transport has been suggested to function via a sliding mechanism involving several sugar binding sites (Cunningham et al., 2006). Glut1 is the receptor for human T-cell leukemia virus (HTLV)) (Manel et al., 2003). The orientation of the 12 TMSs and the conformation of the exofacial glucose binding site of GLUT1 have been proposed (Mueckler and Makepeace 2004). It is regulated by stomatin (TC# 8.A.21) to take up dehydroascorbate (Montel-Hagen et al., 2008). Mutations cause Glut1 deficiency syndrome, a human encephalopathy that results from decreased glucose flux through the blood brain barrier (Pascual et al., 2008).  Mueckler and Makepeace (2009) have presented a model of the exofacial substrate-binding site and helical folding of Glut1. Glut1, 2, 4 and 9 are functional both in the plasma membrane and the endoplasmic reticulum (Takanaga and Frommer, 2010). Glut1 is down-regulated in the brains of Alzheimer's disease patients (Liu et al., 2008b). Metabolic stress rapidly stimulates blood-brain barrier endothelial cell sugar transport by acute up-regulation of plasma membrane GLUT1 levels, possibly involving an AMP-activated kinase activity (Cura and Carruthers, 2010). Serves as a receptor for neuropilin-1 (923aas; 2 TMSs; O14786) and heparan sulfate proteoglycans (HSPGs) (Hoshino, 2012). Glut1 has a nucleotide binding site, and nucleotide binding affects transport activity (Yao and Bajjalieh 2009).  The protein serves as a receptor for dermatin and β-adducin which help link the spectrin-actin junctional complex to the erythrocyte plasma membrane (Khan et al. 2008).  May play a role in paroxysmal dyskinesias (Erro et al. 2017). GLUT1 mediates infection of CD4+ lymphocytes by human T cell leukemia virus type 1 (Jin et al. 2006). Mutations in disordered regions can cause disease by introducing dileucine motifs, For example, mutations that are causative of GLUT1 deficiency syndrome are of this type, and the mutated protein mislocalizes to intracellular compartments (Meyer et al. 2018). Glucose transits along a transmembrane pathway through significant rotational motions while maintaining hydrogen bonds with the protein (Galochkina et al. 2019). It is phosphoryated by protein kinase C-B (TC# 8.A.104.1.4) (Lee et al. 2015). GLUT1-mediated exchange of fluorosugars has been studied (Shishmarev et al. 2018). Resveratrol and soy isoflavones alone and in combination improve the learning and memory of aging rats. The mechanism may be related to up-regulating the expression of GLUT1 and GLUT3 genes in the hippocampus (Zhang et al. 2020). The pore diameters of the transmembrane glucose transporters of all Class I GLUT proteins are constricted upon depletion of unsaturated fatty acids in the membranes (Weijers 2020). Diclofenac inhibits tumor cell glycolysis and growth by decreasing GLUT1 expression (Yang et al. 2021). Almost the entire populations of Glut1 and three other transmembrane proteins are immobilized by either the incorporation within large multiprotein complexes or entrapment within the protein network of the cortical spectrin cytoskeleton (Kodippili et al. 2020). This system is required for hepatocellular carcinoma proliferation and metastasis (Fang et al. 2021). The main triggers FoR activation of transport are located within the solvent accessible linker regions in the extramembranous zones (Gonzalez-Resines et al. 2021). DHHC9-mediated GLUT1 S-palmitoylation is requuired for plasma membrane localization and promotes glioblastoma glycolysis and tumorigenesis (Zhang et al. 2021). An ancient family of arrestin-fold proteins, termed alpha-arrestins, have conserved roles in regulating nutrient transporter trafficking and cellular metabolism as adaptor proteins. One alpha-arrestin, TXNIP (thioredoxin-interacting protein), is known to regulate myocardial glucose uptake, but the in vivo role of the related alpha-arrestin, ARRDC4 (arrestin domain-containing protein 4), was unknown. Interactions of ARRDC4 with GLUT1 prove to mediate metabolic stress in the ischemic heart (Nakayama et al. 2022). Mercury (Hg²⁺) decreased membrane deformability, impairing RBC capacity to deal with the shear forces in the circulation, increasing membrane fragmentation, and affecting transport (Notariale et al. 2022). GLUT-1 and GLUT-3 play important roles in the development of some types of malignant tumors, including glioblastoma, and expression of both is regulated by miRNAs (Beylerli et al. 2022). Glucose uptake inhibitors via Glut1 are potential anticancer agents (Hung et al. 2022). GLUT1 deficiency syndrome (GLUT1DS1) is a rare genetic metabolic disease, characterized by infantile-onset epileptic encephalopathy, global developmental delay, progressive microcephaly, and movement disorders (e.g., spasticity and dystonia) (Mauri et al. 2022). It is caused by heterozygous mutations in the SLC2A1 gene, which encodes the GLUT1 protein, a glucose transporter across the blood-brain barrier (BBB). Most commonly, these variants (~2 dozen) arise de novo, resulting in sporadic cases, although several familial cases with AD inheritance pattern have been described (Mauri et al. 2022). Fluoride exposure affects the expression of glucose transporters (GLUT1 and 3) and ATP synthesis (Chen et al. 2023). GLUT1 is necessary for the flexor digitorum brevis (FDB) to survive hypoxia, but overexpression of GLUT1 was insufficient to rescue other skeletal muscles from hypoxic damage (Amorese et al. 2023). The role of GLUT inhibitors, micro-RNAs, and long non-coding RNAs that aid in inhibiting glucose uptake by cancer cells have been discussed as potential theraputics (Chamarthy and Mekala 2023). GLUT1 overexpression in tumor cells is a potential target for drug therapy (Zhao et al. 2023). HSP90B1-mediated plasma membrane localization of GLUT1 promotes radioresistance of glioblastomas (Li et al. 2023).  The core genes (Fgf2, Pdgfra, Ptpn11, Slc2a1) are highly expressed in sevoflurane anesthesia brain tissue samples. The 4 core genes (Fgf2, Pdgfra, Ptpn11, and Slc2a1) are associated with neurodegenerative diseases, brain injuries, memory disorders, cognitive disorders, neurotoxicity, drug-induced abnormalities, neurological disorders, developmental disorders, and intellectual disabilities. Fgf2 and Ptpn11 are highly expressed in brain tissue after sevoflurane anesthesia, the higher the expression level of Fgf2 and Ptpn11, the worse the prognosis (Zhang and Xu 2023). Target separation and potential anticancer activity of withanolide-based glucose transporter protein 1 inhibitors from Physalis angulata var. villosa have been evaluated (Zhang et al. 2023).  PIGT is a subunit of the glycosylphosphatidylinositol transamidase which is involved in tumorigenesis and invasiveness.  PIGT promotes cell growth, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking (Tan et al. 2024).  PDGF-stimulated glucose uptake via Glut1 has been reported to be dependent on receptor/transporter endocytosis (Tsutsumi et al. 2024).  Glucose transporter-1 deficiency syndrome gives rise to extreme phenotypic variability in a five-generation family carrying a novel SLC2A1 variant (Giugno et al. 2024).  A 4-furanylvinylquinoline derivative is a new scaffold for the design of oxidative stress initiator and a glucose transporter inhibitor via GLUT1 (Kuczak et al. 2024).