Insight into the “odd” hexose transporters GLUT3, GLUT5, and GLUT7
2008; American Physiological Society; Volume: 295; Issue: 2 Linguagem: Inglês
10.1152/ajpendo.90406.2008
ISSN1522-1555
Autores Tópico(s)Amino Acid Enzymes and Metabolism
ResumoEDITORIAL FOCUSInsight into the "odd" hexose transporters GLUT3, GLUT5, and GLUT7Annette SchürmannAnnette SchürmannPublished Online:01 Aug 2008https://doi.org/10.1152/ajpendo.90406.2008This is the final version - click for previous versionMoreSectionsPDF (143 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat glucose transport facilitators (GLUT proteins) mediate the transport of glucose and other monosaccharides into and out of mammalian cells and therefore play a pivotal role in maintaining blood glucose concentrations in a normal range between 4.5 and 6 mM (14). In addition, GLUT proteins are involved in the glucose-sensing machinery; e.g., in pancreatic β-cells, GLUT2 participates in the regulation of glucose-stimulated insulin secretion. Screening the literature results in a large number of publications on the insulin-regulated glucose transporter GLUT4 (7, 8), which is without question, together with GLUT2, a prominent transporter required for maintenance of glucose homeostasis and affected in diseases such as obesity and type 2 diabetes. However, since the late 1990s, we have known that the whole family of human GLUT proteins consists of 14 members (9, 14, 17, 18), indicating that glucose delivery into cells is a process of considerable complexity. The various transporters exhibit different substrate specificities, kinetic properties, and tissue expression profiles (Fig. 1). The fact that certain tissues and cells express two or even more glucose transporter isoforms indicates that the organism developed a backup system assuring adequate energy supply. For instance, spermatozoa and their precursor cells express several transporters: GLUT3, -5, -8, and -9, which guarantees fuel supply and function of spermatozoa even when hexose transport via one of the GLUT proteins is impaired.A series of minireviews in this issue on facilitative hexose transporters summarizes earlier and recent developments defining the specific roles of GLUT3, GLUT5, and GLUT7 in normal and morbid states. GLUT3 is a high-affinity glucose transporter, GLUT5 is a specific fructose transporter, while GLUT7 transports both glucose and fructose with high affinity.Glucose is the obligate energetic source for the mammalian brain, and it is assumed that the majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism (15). GLUT1 is located in the microvascular endothelial cells of the blood-brain barrier and delivers glucose from the circulation to the brain, and GLUT3 mediates glucose transport into neurons. However, GLUT3 is also expressed in other cells (sperm and pre- and postimplantaion embryo, circulating white blood cells, and carcinoma cells) where it triggers the specific requirements for glucose. The review by Simpson et al. (16) discusses the properties for GLUT3, its expression, subcellular distribution, and regulation and focuses on features that make GLUT3 unique within the GLUT family.GLUT5 is the best-characterized fructose transporter and is expressed in several cell types and tissues (intestine, testis, kidney, skeletal muscle, fat, and brain). These days, GLUT5 is of tremendous interest because total fructose consumption has increased dramatically, e.g., in the United States from ∼20 to ∼80 g/day in the last 20–30 years (2). Increased fructose consumption, in particular as carbonated beverages, has been attributed to participate in the increased prevalence of obesity and type 2 diabetes. Fructose is absorbed in the jejunum and transferred (13) through the apical membrane of epithelial cells into the portal circulation (3). In the liver, fructose is phosphorylated to fructose 1-phosphate and converted to glycerol 3-phosphate for the synthesis of glycerol (6) or metabolized to acetyl-CoA and incorporated into fatty acids, while only a small portion is converted into glucose (1). Therefore, the preferential entry of fructose into lipogenesis might contribute to the effects of fructose to induce hyperlipidemia and to increased serum triglyceride levels (10). Several members of the GLUT family are able to transport fructose (GLUT2, -5, -7, -8, -9, -11, and -12), but only GLUT5 exclusively transports fructose. The review by Dourard and Ferraris (5) focuses on alterations of GLUT5 expression and fructose uptake in diabetes, hypertension, obesity, and inflammation. It also gives important information on the role of GLUT5 during intestine development, metabolic disturbances, and cancer.A closely related protein of GLUT5 is GLUT7, bearing 53% identity. It is a high-affinity transporter for glucose and fructose and is mainly expressed in the brush-border membrane of the small intestine and in the colon (11). Other intestinal glucose transporters, SGLT1, GLUT2, and GLUT5 are expressed in the jejunum, whereas the distribution of GLUT7 is limited to the distal region of the small intestine, the ileum, which does not contain high concentrations of glucose and fructose. This observation suggested that GLUT7 does not play a major role in taking up glucose and fructose from the diet but that it may be important toward the end of a meal when luminal concentrations of hexoses in the ileum are low (11). Comparison of sequence alignments and mutation studies on GLUT7 identified a specific hydrophobic residue in transmembrane domain 7 that determines the specificity for fructose (12). Several mutational studies mainly performed in GLUT1 and GLUT4 lead to the concept that GLUT proteins undergo specific conformational changes during the passage of the hexose. It is believed that its binding to the outward-facing binding site induces a conformational alteration that moves the substrate through the pore of the GLUT protein. Thereafter, the substrate is released from the inward-facing binding site to the cytoplasm, and the transporter undergoes the reverse conformational change (9). The review on GLUT7 by C. Cheeseman (4), who discovered GLUT7 as the latest member of the GLUT family, introduces the hypothesis that GLUT proteins may have a selectivity filter at the exofacial site which helps to determine which substrate is transported. Fig. 1.Dendrogram of the family of human hexose transporters and major sites of expression (see Ref. 14). Numbers at the branches of the tree indicate percentage of identity.Download figureDownload PowerPointREFERENCES1 Aoyama Y, Yoshida A, Ashida K. Effect of dietary fats and fatty acids on the liver lipid accumulation induced by feeding a protein-repletion diet containing fructose to protein-depleted rats. J Nutr 104: 741–746, 1974.Crossref | PubMed | ISI | Google Scholar2 Bray GA. How bad is fructose? Am J Clin Nutr 86: 895–896, 2007.Crossref | PubMed | ISI | Google Scholar3 Busserolles J, Gueux E, Rock E, Mazur A, Rayssiguier Y. Substituting honey for refined carbohydrates protects rats from hypertriglyceridemic and prooxidative effects of fructose. J Nutr 132: 3379–3382, 2002.Crossref | PubMed | ISI | Google Scholar4 Cheeseman CI. GLUT7, a class II high-affinity intestinal glucose/fructose facilitated hexose transporter. 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Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89: 3–9, 2003.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: A. Schürmann, Dept. of Pharmacology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany (e-mail: [email protected]) Download PDF Back to Top Next FiguresReferencesRelatedInformation Cited ByHoney and Its Molecular Pharmacology: An Essay15 December 2020Genome-wide identification and characterization of glucose transporter (glut) genes in spotted sea bass (Lateolabrax maculatus) and their regulated hepatic expression during short-term starvationComparative Biochemistry and Physiology Part D: Genomics and Proteomics, Vol. 30Plasma lactate, insulin concentration and intestinal glycogen deposition responses to fructose infusion in male dogs31 October 2018 | Journal of Physiology and Pathophysiology, Vol. 9, No. 2Honey as a Potential Natural Antioxidant Medicine: An Insight into Its Molecular Mechanisms of ActionOxidative Medicine and Cellular Longevity, Vol. 2018Fibromyalgia Syndrome: A Metabolic Approach Grounded in Biochemistry for the Remission of Symptoms13 November 2017 | Frontiers in Medicine, Vol. 4Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose intolerance1 February 2014 | United European Gastroenterology Journal, Vol. 2, No. 1Correlation between Expression of Glucose Transporters in Granulosa Cells and Oocyte Quality in Women with Polycystic Ovary SyndromeEndocrinology and Metabolism, Vol. 29, No. 1Role of Monosaccharide Transport Proteins in Carbohydrate Assimilation, Distribution, Metabolism, and Homeostasis1 April 2012Fructose Might Contribute to the Hypoglycemic Effect of Honey15 February 2012 | Molecules, Vol. 17, No. 2 More from this issue > Volume 295Issue 2August 2008Pages E225-E226 Copyright & PermissionsCopyright © 2008 by American Physiological Societyhttps://doi.org/10.1152/ajpendo.90406.2008PubMed18460594History Published online 1 August 2008 Published in print 1 August 2008 Metrics
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