Wikipedia

Glucose transporter

(Redirected from Glucose transporter type 4)

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.

Sugar_tr
Identifiers
SymbolSugar_tr
PfamPF00083
Pfam clanCL0015
InterProIPR005828
PROSITEPDOC00190
TCDB2.A.1.1
OPM superfamily15
OPM protein4gc0
CDDcd17315
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Glucose

Synthesis of free glucose

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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

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In Saccharomyces cerevisiae glucose transport takes place through facilitated diffusion.[1] The transport proteins are mainly from the Hxt family, but many other transporters have been identified.[2]

Name Properties Notes
Snf3 low-glucose sensor; repressed by glucose; low expression level; repressor of Hxt6
Rgt2 high-glucose sensor; low expression level
Hxt1 Km: 100 mM,[3] 129 - 107 mM[1] low-affinity glucose transporter; induced by high glucose level
Hxt2 Km = 1.5[1] - 10 mM[3] high/intermediate-affinity glucose transporter; induced by low glucose level[3]
Hxt3 Vm = 18.5, Kd = 0.078, Km = 28.6/34.2[1] - 60 mM[3] low-affinity glucose transporter[3]
Hxt4 Vm = 12.0, Kd = 0.049, Km = 6.2[1] intermediate-affinity glucose transporter[3]
Hxt5 Km = 10 mM[4] Moderate glucose affinity. Abundant during stationary phase, sporulation and low glucose conditions. Transcription repressed by glucose.[4]
Hxt6 Vm = 11.4, Kd = 0.029, Km = 0.9/14,[1] 1.5 mM[3] high glucose affinity[3]
Hxt7 Vm = 11.7, Kd = 0.039, Km = 1.3, 1.9,[1] 1.5 mM[3] high glucose affinity[3]
Hxt8 low expression level[3]
Hxt9 involved in pleiotropic drug resistance[3]
Hxt11 involved in pleiotropic drug resistance[3]
Gal2 Vm = 17.5, Kd = 0.043, Km = 1.5, 1.6[1] high galactose affinity[3]

Glucose transport in mammals

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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,[5][6][7] 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;[8] also, the DLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.[9][10]

Types

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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.[11] To date, 14 members of the GLUT/SLC2 have been identified.[12] On the basis of sequence similarities, the GLUT family has been divided into three subclasses.

Class I

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Class I comprises the well-characterized glucose transporters GLUT1-GLUT4.[13]

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.[12]
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 [12]

Classes II/III

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Class II comprises:

Class III comprises:

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?] 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

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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.[15] Crane's discovery of cotransport was the first ever proposal of flux coupling in biology.[16] 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.[17]

See also

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References

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  1. ^ a b c d e f g h Maier A, Völker B, Boles E, Fuhrmann GF (December 2002). "Characterisation of glucose transport in Saccharomyces cerevisiae with plasma membrane vesicles (countertransport) and intact cells (initial uptake) with single Hxt1, Hxt2, Hxt3, Hxt4, Hxt6, Hxt7 or Gal2 transporters". FEMS Yeast Research. 2 (4): 539–50. doi:10.1111/j.1567-1364.2002.tb00121.x. PMID 12702270.
  2. ^ "List of possible glucose transporters in S. cerevisiae". UniProt.
  3. ^ a b c d e f g h i j k l m n Boles E, Hollenberg CP (August 1997). "The molecular genetics of hexose transport in yeasts". FEMS Microbiology Reviews. 21 (1): 85–111. doi:10.1111/j.1574-6976.1997.tb00346.x. PMID 9299703.
  4. ^ a b Diderich JA, Schuurmans JM, Van Gaalen MC, Kruckeberg AL, Van Dam K (December 2001). "Functional analysis of the hexose transporter homologue HXT5 in Saccharomyces cerevisiae". Yeast. 18 (16): 1515–24. doi:10.1002/yea.779. PMID 11748728. S2CID 22968336.
  5. ^ Oka Y, Asano T, Shibasaki Y, Lin JL, Tsukuda K, Katagiri H, Akanuma Y, Takaku F (June 1990). "C-terminal truncated glucose transporter is locked into an inward-facing form without transport activity". Nature. 345 (6275): 550–3. Bibcode:1990Natur.345..550O. doi:10.1038/345550a0. PMID 2348864. S2CID 4264399.
  6. ^ Hebert DN, Carruthers A (November 1992). "Glucose transporter oligomeric structure determines transporter function. Reversible redox-dependent interconversions of tetrameric and dimeric GLUT1". The Journal of Biological Chemistry. 267 (33): 23829–38. doi:10.1016/S0021-9258(18)35912-X. PMID 1429721.
  7. ^ Cloherty EK, Sultzman LA, Zottola RJ, Carruthers A (November 1995). "Net sugar transport is a multistep process. Evidence for cytosolic sugar binding sites in erythrocytes". Biochemistry. 34 (47): 15395–406. doi:10.1021/bi00047a002. PMID 7492539.
  8. ^ Hruz PW, Mueckler MM (2001). "Structural analysis of the GLUT1 facilitative glucose transporter (review)". Molecular Membrane Biology. 18 (3): 183–93. doi:10.1080/09687680110072140. PMID 11681785.
  9. ^ Seatter MJ, De la Rue SA, Porter LM, Gould GW (February 1998). "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". Biochemistry. 37 (5): 1322–6. doi:10.1021/bi972322u. PMID 9477959.
  10. ^ Hruz PW, Mueckler MM (December 1999). "Cysteine-scanning mutagenesis of transmembrane segment 7 of the GLUT1 glucose transporter". The Journal of Biological Chemistry. 274 (51): 36176–80. doi:10.1074/jbc.274.51.36176. PMID 10593902.
  11. ^ Thorens B (April 1996). "Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes". The American Journal of Physiology. 270 (4 Pt 1): G541-53. doi:10.1152/ajpgi.1996.270.4.G541. PMID 8928783.
  12. ^ a b c d e Thorens B, Mueckler M (February 2010). "Glucose transporters in the 21st Century". American Journal of Physiology. Endocrinology and Metabolism. 298 (2): E141-5. doi:10.1152/ajpendo.00712.2009. PMC 2822486. PMID 20009031.
  13. ^ Bell GI, Kayano T, Buse JB, Burant CF, Takeda J, Lin D, Fukumoto H, Seino S (March 1990). "Molecular biology of mammalian glucose transporters". Diabetes Care. 13 (3): 198–208. doi:10.2337/diacare.13.3.198. PMID 2407475. S2CID 20712863.
  14. ^ Boron WF (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 995. ISBN 978-1-4160-2328-9.
  15. ^ Crane RK, Miller D, Bihler I (1961). "The restrictions on possible mechanisms of intestinal transport of sugars". In Kleinzeller A, Kotyk A (eds.). Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Prague: Czech Academy of Sciences. pp. 439–449.
  16. ^ Wright EM, Turk E (February 2004). "The sodium/glucose cotransport family SLC5". Pflügers Archiv. 447 (5): 510–8. doi:10.1007/s00424-003-1063-6. PMID 12748858. S2CID 41985805.
  17. ^ Boyd CA (March 2008). "Facts, fantasies and fun in epithelial physiology". Experimental Physiology. 93 (3): 303–14. doi:10.1113/expphysiol.2007.037523. PMID 18192340. S2CID 41086034. 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.
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