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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/18 07:08:24」(JST)

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Glucose

Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. 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.

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 only produced 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.^[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-affinityglucose 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

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 QLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.^[9]^[10]

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.^[11] To date, 13 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

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. However, 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.
GLUT2	Is a bidirectional transporter, allowing glucose to flow in 2 directions. Is expressed by renal tubular cells, small intestinal epithelial cells, liver cells and pancreatic beta cells. Bidirectionality is required in liver cells to uptake glucose for glycolysis, 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-capacity and low-affinity isoform. There is some evidence that GLUT 1 and 3 are actually the functional transporters in beta cells.
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	Found in adipose tissues and striated muscle (skeletal muscle and cardiac muscle).	Is the insulin-regulated glucose transporter. Responsible for insulin-regulated glucose storage.

Classes II/III

Class II comprises:

GLUT5 (SLC2A5), a fructose transporter
GLUT7 - SLC2A7 - (SLC2A7), transporting glucose out of the endoplasmic reticulum ^[14]
GLUT9 - SLC2A9 - (SLC2A9)
GLUT11 (SLC2A11)

Class III comprises:

GLUT6 (SLC2A6),
GLUT8 (SLC2A8),
GLUT10 (SLC2A10),
GLUT12 (SLC2A12), and
the H+/myoinositol transporter HMIT (SLC2A13).^[15]

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 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.^[16] Crane's discovery of cotransport was the first ever proposal of flux coupling in biology.^[17]^[18]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h Maier A, Asano T, Volker A, Boles E, Fuhrmann G F (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): 539–550. doi:10.1111/j.1567-1364.2002.tb00121.x. PMID 12702270.
^ uniprot list of possible glucose transporters in S. cerevisiae
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ Boles E, Hollenberg C P (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.
^ ^a ^b Diderich J A, Schuurmans J M, Gaalen M C, Kruckeberg A L, Van Dam K (2001). "Functional analysis of the hexose transporter homologue HXT5 in Saccharomyces cerevisiae". Yeast 18 (16): 1515–1524. doi:10.1002 / yea.779. PMID 11748728.
^ Oka Y, Asano T, Shibasaki Y, Lin J, Tsukuda K, Katagiri H, Akanuma Y, Takaku F (1990). "C-terminal truncated glucose transporter is locked into an inward-facing form without transport activity". Nature 345 (6275): 550–3. doi:10.1038/345550a0. PMID 2348864.
^ Hebert D, Carruthers A (1992). "Glucose transporter oligomeric structure determines transporter function. Reversible redox-dependent interconversions of tetrameric and dimeric GLUT1". J. Biol. Chem. 267 (33): 23829–38. PMID 1429721.
^ Cloherty E, Sultzman L, Zottola R, Carruthers A (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.
^ Hruz P, Mueckler M (2001). "Structural analysis of the GLUT1 facilitative glucose transporter (review)". Mol. Membr. Biol. 18 (3): 183–93. doi:10.1080/09687680110072140. PMID 11681785.
^ Seatter M, De la Rue S, Porter L, Gould G (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.
^ Hruz P, Mueckler M (1999). "Cysteine-scanning mutagenesis of transmembrane segment 7 of the GLUT1 glucose transporter". J. Biol. Chem. 274 (51): 36176–80. doi:10.1074/jbc.274.51.36176. PMID 10593902.
^ Thorens B (1996). "Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes". Am. J. Physiol. 270 (4 Pt 1): G541–53. PMID 8928783.
^ Joost H, Thorens B (2001). "The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review)". Mol. Membr. Biol. 18 (4): 247–56. doi:10.1080/09687680110090456. PMID 11780753.
^ Bell G, Kayano T, Buse J, Burant C, Takeda J, Lin D, Fukumoto H, Seino S (1990). "Molecular biology of mammalian glucose transporters". Diabetes Care 13 (3): 198–208. doi:10.2337/diacare.13.3.198. PMID 2407475.
^ Page 995 in: Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 1300. ISBN 1-4160-2328-3.
^ Uldry M, Thorens B (2004). "The SLC2 family of facilitated hexose and polyol transporters". Pflugers Arch. 447 (5): 480–9. doi:10.1007/s00424-003-1085-0. PMID 12750891.
^ Robert K. Crane, D. Miller and I. Bihler. “The restrictions on possible mechanisms of intestinal transport of sugars”. In: Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A. Kotyk. Czech Academy of Sciences, Prague, 1961, pp. 439-449.
^ Ernest M. Wright and Eric Turk. “The sodium glucose cotransport family SLC5”. Pflügers Arch 447, 2004, p. 510. “Crane in 1961 was the first to formulate the cotransport concept to explain active transport [7]. 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.”
^ Boyd, C A R. “Facts, fantasies and fun in epithelial physiology”. Experimental Physiology, Vol. 93, Issue 3, 2008, p. 304. “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.”

External links

Glucose+Transport+Proteins,+Facilitative at the US National Library of Medicine Medical Subject Headings (MeSH)

English Journal

Putting into practice domain-linear motif interaction predictions for exploration of protein networks.

Luck K, Fournane S, Kieffer B, Masson M, Nominé Y, Travé G.SourceGroup Onco-Proteins, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, Illkirch, France.
PloS one.PLoS One.2011;6(11):e25376. Epub 2011 Nov 1.
PDZ domains recognise short sequence motifs at the extreme C-termini of proteins. A model based on microarray data has been recently published for predicting the binding preferences of PDZ domains to five residue long C-terminal sequences. Here we investigated the potential of this predictor for dis
PMID 22069443

Expression of mRNA for glucose transport proteins in jejunum, liver, kidney and skeletal muscle of pigs.

Aschenbach JR, Steglich K, Gäbel G, Honscha KU.SourceInstitute of Veterinary Physiology, University of Leipzig, An den Tierkliniken 7, D-04103 Leipzig, Germany. joerg.aschenbach@vetmeduni.ac.at
Journal of physiology and biochemistry.J Physiol Biochem.2009 Sep;65(3):251-66.
Although pigs are adapted to starch-rich diets and have high turnover rates of glucose, very scarce information is available on the molecular basis of glucose transport. Therefore, the present study attempted a systematic screening for the presence of mRNA of glucose transport proteins in main organ
PMID 20119820

Related Pictures

★リンクテーブル★

リンク元	「グルコース輸送体」
関連記事	「GLUT」

「グルコース輸送体」

　　[★]

英: glucose transporter, GLUT, glucose transporters
同: ブドウ糖輸送担体、糖輸送体糖輸送担体 sugar transporter

グルコースの促通拡散を担う

GLUTの種類

GLUT	発現部位	機能
GLUT1	赤血球、脳、筋肉、脂肪、その他。×肝臓
GLUT2	肝臓、脾臓β細胞	K_M≒60mM、hexokinase IV(glucokinase)(50kDa)
GLUT3	脳、神経	グルコース需要が多い場所で発現
GLUT4	筋と脂肪組織のみ	インスリン→V_max↑。K_M=2-5mM、hexokinase II(100kDa)
GLUT5	小腸上皮管腔側	フルクトースの受動輸送
GLUT7	肝臓小胞体	G6Pの脱リン酸化に関与(FB. 453)

-GLUT

-GLUT

「GLUT」

　　[★] グルコース輸送体 glucose transporter glucose transporters

[Maier-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h Maier A, Asano T, Volker A, Boles E, Fuhrmann G F (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): 539–550. doi:10.1111/j.1567-1364.2002.tb00121.x. PMID 12702270.

[2] uniprot list of possible glucose transporters in S. cerevisiae

[molgen-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ Boles E, Hollenberg C P (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.

[SILS-4] Diderich J A, Schuurmans J M, Gaalen M C, Kruckeberg A L, Van Dam K (2001). "Functional analysis of the hexose transporter homologue HXT5 in Saccharomyces cerevisiae". Yeast 18 (16): 1515–1524. doi:10.1002 / yea.779. PMID 11748728.

[5] Oka Y, Asano T, Shibasaki Y, Lin J, Tsukuda K, Katagiri H, Akanuma Y, Takaku F (1990). "C-terminal truncated glucose transporter is locked into an inward-facing form without transport activity". Nature 345 (6275): 550–3. doi:10.1038/345550a0. PMID 2348864.

[6] Hebert D, Carruthers A (1992). "Glucose transporter oligomeric structure determines transporter function. Reversible redox-dependent interconversions of tetrameric and dimeric GLUT1". J. Biol. Chem. 267 (33): 23829–38. PMID 1429721.

[7] Cloherty E, Sultzman L, Zottola R, Carruthers A (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 P, Mueckler M (2001). "Structural analysis of the GLUT1 facilitative glucose transporter (review)". Mol. Membr. Biol. 18 (3): 183–93. doi:10.1080/09687680110072140. PMID 11681785.

[9] Seatter M, De la Rue S, Porter L, Gould G (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 P, Mueckler M (1999). "Cysteine-scanning mutagenesis of transmembrane segment 7 of the GLUT1 glucose transporter". J. Biol. Chem. 274 (51): 36176–80. doi:10.1074/jbc.274.51.36176. PMID 10593902.

[11] Thorens B (1996). "Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes". Am. J. Physiol. 270 (4 Pt 1): G541–53. PMID 8928783.

[12] Joost H, Thorens B (2001). "The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review)". Mol. Membr. Biol. 18 (4): 247–56. doi:10.1080/09687680110090456. PMID 11780753.

[13] Bell G, Kayano T, Buse J, Burant C, Takeda J, Lin D, Fukumoto H, Seino S (1990). "Molecular biology of mammalian glucose transporters". Diabetes Care 13 (3): 198–208. doi:10.2337/diacare.13.3.198. PMID 2407475.

[boron995-14] Page 995 in: Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 1300. ISBN 1-4160-2328-3.

[15] Uldry M, Thorens B (2004). "The SLC2 family of facilitated hexose and polyol transporters". Pflugers Arch. 447 (5): 480–9. doi:10.1007/s00424-003-1085-0. PMID 12750891.

[16] Robert K. Crane, D. Miller and I. Bihler. “The restrictions on possible mechanisms of intestinal transport of sugars”. In: Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A. Kotyk. Czech Academy of Sciences, Prague, 1961, pp. 439-449.

[17] Ernest M. Wright and Eric Turk. “The sodium glucose cotransport family SLC5”. Pflügers Arch 447, 2004, p. 510. “Crane in 1961 was the first to formulate the cotransport concept to explain active transport [7]. 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.”

[18] Boyd, C A R. “Facts, fantasies and fun in epithelial physiology”. Experimental Physiology, Vol. 93, Issue 3, 2008, p. 304. “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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GLUT7