Functional Properties and Genomics of Glucose Transporters

Abstract

Glucose is the major energy source for mammalian cells as well as an important substrate for protein and lipid synthesis. Mammalian cells take up glucose from extracellular fluid into the cell through two families of structurallyrelated glucose transporters. The facilitative glucose transporter family (solute carriers SLC2A, protein symbol GLUT) mediates a bidirectional and energy-independent process of glucose transport in most tissues and cells, while the Na + /glucose cotransporter family (solute carriers SLC5A, protein symbol SGLT) mediates an active, Na + -linked transport process against an electrochemical gradient. The GLUT family consists of thirteen members (GLUT1-12 and HMIT). Phylogenetically, the members of the GLUT family are split into three classes based on protein similarities. Up to now, at least six members of the SGLT family have been cloned (SGLT1-6). In this review, we report both the genomic structure and function of each transporter as well as intra-species comparative genomic analysis of some of these transporters. The affinity for glucose and transport kinetics of each transporter differs and ranges from 0.2 to 17mM. The ability of each protein to transport alternative substrates also differs and includes substrates such as fructose and galactose. In addition, the tissue distribution pattern varies between species. There are different regulation mechanisms of these transporters. Characterization of transcriptional control of some of the gene promoters has been investigated and alternative promoter usage to generate different protein isoforms has been demonstrated. We also introduce some pathophysiological roles of these transporters in human.

Positron emission tomography probe demonstrates a striking concentration of ribose salvage in the liver

“…An earlier study indicates that Cytochalasin B, a promiscuous small-molecule ligand that binds to and blocks glucose transport through the Slc2a family of glucose transporters (19), blocks ribose salvage in cultured mammalian cells (20). The best-studied hepatic Slc2a transporter is Slc2a2 (also known as GLUT2) (21). In agreement with previous reports (22), we found that Slc2a2 mRNA levels are enriched in the liver, kidneys, and intestines (Fig.…”

“…Hepatic phenotypes of patients with Fanconi-Bickel syndrome include hepatomegaly and enhanced glycogen accumulation (48). Slc2a2 is a high-capacity glucose transporter (21), and many phenotypes found in Slc2a2 KO mice and patients with Fanconi-Bickel syndrome are likely caused by altered glucose consumption. However, we show that Slc2a2 also transports ribose.…”

Glucose‐6‐phosphate metabolism in Plasmodium falciparum

“…In order to be transported into the parasite, glucose has to cross several membranes (Fig. 2); it is transported into the erythrocyte by the facilitative glucose transporter GLUT1 located in the erythrocyte plasma membrane (43) and can freely pass the parasitophorous vacuole membrane (44). Finally, glucose is transported over the parasite plasma membrane via P. falciparum hexose transporter (PfHT), the primary glucose transporter that can also transport fructose (45).…”

Characterization and expression pattern analysis of the facilitative glucose transporter 10 gene (slc2a10) in Danio rerio

“…These residues are important for substrate recognition and sugar transport specificity (Barrett et al, 1999;McVieWylie et al, 2001;Dawson et al, 2001). Interestingly, zebrafish Glut10 does not have the PESPR motif in loop 6 present in all GLUTs, which may contribute to its low-rate saturable glucose transport activity (Dawson et al, 2001;Zhao and Keating, 2007).…”