glucose transporter
{{Short description|Family of monosaccharide transport proteins}}
{{Infobox protein family
| Symbol = Sugar_tr
| Name = Sugar_tr
| image =
| width =
| caption =
| Pfam = PF00083
| Pfam_clan = CL0015
| InterPro = IPR005828
| SMART =
| PROSITE = PDOC00190
| MEROPS =
| SCOP =
| TCDB = 2.A.1.1
| OPM family = 15
| OPM protein = 4gc0
| CAZy =
| CDD = cd17315
}}
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporters are present in all phyla. The GLUT or SLC2A family are a protein family that is found in most mammalian cells. 14 GLUTS are encoded by the human genome. GLUT is a type of uniporter transporter protein.
Synthesis of free glucose
Most non-autotrophic cells are unable to produce free glucose because they lack expression of glucose-6-phosphatase and, thus, are involved only in glucose uptake and catabolism. Usually produced only in hepatocytes, in fasting conditions, other tissues such as the intestines, muscles, brain, and kidneys are able to produce glucose following activation of gluconeogenesis.
Glucose transport in yeast
In Saccharomyces cerevisiae glucose transport takes place through facilitated diffusion. The transport proteins are mainly from the Hxt family, but many other transporters have been identified.{{cite web | url = https://www.uniprot.org/uniprot/?query=glucose+transporter&sort=organism&desc=false&page=94 | work = UniProt | title = List of possible glucose transporters in S. cerevisiae }}
Glucose transport in mammals
GLUTs are integral membrane proteins that contain 12 membrane-spanning helices with both the amino and carboxyl termini exposed on the cytoplasmic side of the plasma membrane. GLUT proteins transport glucose and related hexoses according to a model of alternate conformation,{{cite journal | vauthors = Oka Y, Asano T, Shibasaki Y, Lin JL, Tsukuda K, Katagiri H, Akanuma Y, Takaku F | title = C-terminal truncated glucose transporter is locked into an inward-facing form without transport activity | journal = Nature | volume = 345 | issue = 6275 | pages = 550–3 | date = June 1990 | pmid = 2348864 | doi = 10.1038/345550a0 | bibcode = 1990Natur.345..550O | s2cid = 4264399 }}{{cite journal | vauthors = Hebert DN, Carruthers A | title = Glucose transporter oligomeric structure determines transporter function. Reversible redox-dependent interconversions of tetrameric and dimeric GLUT1 | journal = The Journal of Biological Chemistry | volume = 267 | issue = 33 | pages = 23829–38 | date = November 1992 | doi = 10.1016/S0021-9258(18)35912-X | pmid = 1429721 | doi-access =free }}{{cite journal | vauthors = Cloherty EK, Sultzman LA, Zottola RJ, Carruthers A | title = Net sugar transport is a multistep process. Evidence for cytosolic sugar binding sites in erythrocytes | journal = Biochemistry | volume = 34 | issue = 47 | pages = 15395–406 | date = November 1995 | pmid = 7492539 | doi = 10.1021/bi00047a002 }} which predicts that the transporter exposes a single substrate binding site toward either the outside or the inside of the cell. Binding of glucose to one site provokes a conformational change associated with transport, and releases glucose to the other side of the membrane. The inner and outer glucose-binding sites are, it seems, located in transmembrane segments 9, 10, 11;{{cite journal | vauthors = Hruz PW, Mueckler MM | title = Structural analysis of the GLUT1 facilitative glucose transporter (review) | journal = Molecular Membrane Biology | volume = 18 | issue = 3 | pages = 183–93 | year = 2001 | pmid = 11681785 | doi = 10.1080/09687680110072140 | doi-access = free }} also, the DLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.{{cite journal | vauthors = Seatter MJ, De la Rue SA, Porter LM, Gould GW | title = QLS motif in transmembrane helix VII of the glucose transporter family interacts with the C-1 position of D-glucose and is involved in substrate selection at the exofacial binding site | journal = Biochemistry | volume = 37 | issue = 5 | pages = 1322–6 | date = February 1998 | pmid = 9477959 | doi = 10.1021/bi972322u }}{{cite journal | vauthors = Hruz PW, Mueckler MM | title = Cysteine-scanning mutagenesis of transmembrane segment 7 of the GLUT1 glucose transporter | journal = The Journal of Biological Chemistry | volume = 274 | issue = 51 | pages = 36176–80 | date = December 1999 | pmid = 10593902 | doi = 10.1074/jbc.274.51.36176 | doi-access = free }}
=Types=
Each glucose transporter isoform plays a specific role in glucose metabolism determined by its pattern of tissue expression, substrate specificity, transport kinetics, and regulated expression in different physiological conditions.{{cite journal | vauthors = Thorens B | title = Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes | journal = The American Journal of Physiology | volume = 270 | issue = 4 Pt 1 | pages = G541-53 | date = April 1996 | pmid = 8928783 | doi = 10.1152/ajpgi.1996.270.4.G541 }} To date, 14 members of the GLUT/SLC2 have been identified.{{cite journal | vauthors = Thorens B, Mueckler M | title = Glucose transporters in the 21st Century | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 298 | issue = 2 | pages = E141-5 | date = February 2010 | pmid = 20009031 | pmc = 2822486 | doi = 10.1152/ajpendo.00712.2009 }} On the basis of sequence similarities, the GLUT family has been divided into three subclasses.
==Class I==
Class I comprises the well-characterized glucose transporters GLUT1-GLUT4.{{cite journal | vauthors = Bell GI, Kayano T, Buse JB, Burant CF, Takeda J, Lin D, Fukumoto H, Seino S | title = Molecular biology of mammalian glucose transporters | journal = Diabetes Care | volume = 13 | issue = 3 | pages = 198–208 | date = March 1990 | pmid = 2407475 | doi = 10.2337/diacare.13.3.198 | s2cid = 20712863 }}
| class="wikitable"
! Name !! Distribution !! Notes | ||
| GLUT1 | Is widely distributed in fetal tissues. In the adult, it is expressed at highest levels in erythrocytes and also in the endothelial cells of barrier tissues such as the blood–brain barrier. It is responsible for the low level of basal glucose uptake required to sustain respiration in all cells. | Levels in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels. GLUT1 expression is upregulated in many tumors. |
| GLUT2 | Is a bidirectional transporter, allowing glucose to flow in 2 directions. Is expressed by renal tubular cells, liver cells and pancreatic beta cells. It is also present in the basolateral membrane of the small intestine epithelium. Bidirectionality is required in liver cells to uptake glucose for glycolysis and glycogenesis, and release of glucose during gluconeogenesis. In pancreatic beta cells, free flowing glucose is required so that the intracellular environment of these cells can accurately gauge the serum glucose levels. All three monosaccharides (glucose, galactose, and fructose) are transported from the intestinal mucosal cell into the portal circulation by GLUT2. | Is a high-frequency and low-affinity isoform. |
| GLUT3 | Expressed mostly in neurons (where it is believed to be the main glucose transporter isoform), and in the placenta. | Is a high-affinity isoform, allowing it to transport even in times of low glucose concentrations. |
| GLUT4 | Expressed in adipose tissues and striated muscle (skeletal muscle and cardiac muscle). | Is the insulin-regulated glucose transporter. Responsible for insulin-regulated glucose storage. |
| GLUT14 | Expressed in testes | similarity to GLUT3 |
==Classes II/III==
Class II comprises:
- GLUT5 ({{Gene|SLC2A5}}), a fructose transporter in enterocytes
- GLUT7 ({{Gene|SLC2A7}}), found in the small and large intestine, transporting glucose out of the endoplasmic reticulum{{cite book | first = Walter F. | last = Boron | name-list-style = vanc |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |year=2003 |isbn=978-1-4160-2328-9 | pages = 995 }}
- GLUT9 ({{Gene|SLC2A9}}), recently has been found to transport uric acid
- GLUT11 ({{Gene|SLC2A11}})
Class III comprises:
- GLUT6 ({{Gene|SLC2A6}}),
- GLUT8 ({{Gene|SLC2A8}}),
- GLUT10 ({{Gene|SLC2A10}}),
- GLUT12 ({{Gene|SLC2A12}}), and
- GLUT13, also H+/myo-inositol transporter HMIT ({{Gene|SLC2A13}}), primarily expressed in brain.
Most members of classes II and III have been identified recently in homology searches of EST databases and the sequence information provided by the various genome projects.
The function of these new{{when|date=May 2023}} glucose transporter isoforms is still not clearly defined at present. Several of them (GLUT6, GLUT8) are made of motifs that help retain them intracellularly and therefore prevent glucose transport. Whether mechanisms exist to promote cell-surface translocation of these transporters is not yet known, but it has clearly been established that insulin does not promote GLUT6 and GLUT8 cell-surface translocation.
=Discovery of sodium-glucose cotransport=
In August 1960, in Prague, Robert K. Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption.{{cite book|author-link1 = Robert K. Crane|vauthors = Crane RK, Miller D, Bihler I|chapter = The restrictions on possible mechanisms of intestinal transport of sugars|title = Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960|veditors = Kleinzeller A, Kotyk A|publisher = Czech Academy of Sciences|location = Prague|date = 1961|pages = 439–449 }} Crane's discovery of cotransport was the first ever proposal of flux coupling in biology.{{cite journal| vauthors = Wright EM, Turk E | title = The sodium/glucose cotransport family SLC5 | journal = Pflügers Archiv | volume = 447 | issue = 5 | pages = 510–8 | date = February 2004 | pmid = 12748858 | doi = 10.1007/s00424-003-1063-6 | s2cid = 41985805 }} Crane in 1961 was the first to formulate the cotransport concept to explain active transport. Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the brush border membrane was [is] coupled to downhill Na+ transport cross the brush border. This hypothesis was rapidly tested, refined, and extended [to] encompass the active transport of a diverse range of molecules and ions into virtually every cell type.{{cite journal|vauthors = Boyd CA|title = Facts, fantasies and fun in epithelial physiology|journal = Experimental Physiology|volume = 93|issue = 3|pages = 303–14|date = March 2008|pmid = 18192340|doi = 10.1113/expphysiol.2007.037523|s2cid = 41086034|quote = The insight from this time that remains in all current text books is the notion of Robert Crane published originally as an appendix to a symposium paper published in 1960 (Crane et al. 1960). The key point here was 'flux coupling', the cotransport of sodium and glucose in the apical membrane of the small intestinal epithelial cell. Half a century later this idea has turned into one of the most studied of all transporter proteins (SGLT1), the sodium–glucose cotransporter.|doi-access = free}}
See also
References
{{reflist}}
External links
- {{MeshName|Glucose+Transport+Proteins,+Facilitative}}
{{Solute carrier family|bg|bg0}}
{{Sodium-glucose transporter modulators}}
Category:Carbohydrate metabolism