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a simple sugar found in honey and in many ripe fruits (同)fruit_sugar, levulose, laevulose

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〈U〉果糖

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/18 13:57:42」(JST)

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Fructose 2,6-bisphosphate abbreviated Fru-2,6-P₂, is a metabolite that allosterically affects the activity of the enzymes phosphofructokinase 1 (PFK-1) and fructose 1,6-bisphosphatase (FBPase-1) to regulate glycolysis and gluconeogenesis.^[1] Fru-2,6-P₂ is synthesized and broken down by the bifunctional enzyme phosphofructokinase 2/fructose-2,6-bisphosphatase (PFK-2/FBPase-2).^[2]

The synthesis of Fru-2,6-P₂ is performed through the phosphorylation of fructose 6-phosphate using ATP by the PFK-2 portion of the enzyme. The breakdown of Fru-2,6-P₂ is catalyzed by dephosphorylation by FBPase-2 to produce Fructose 6-phosphate and P_i.^[3]

Reaction scheme of breakdown of fructose 2,6-bisphosphate to fructose 6-phosphate.^[4]

Effects on glucose metabolism

Fru-2,6-P₂ strongly activates glucose breakdown in glycolysis through allosteric modulation of phosphofructokinase 1 (PFK-1). Elevated expression of Fru-2,6-P₂ levels in the liver allosterically activates phosphofructokinase 1 by increasing the enzyme’s affinity for fructose 6-phosphate, while decreasing its affinity for inhibitory ATP and citrate. At physiological concentration, PFK-1 is almost completely inactive, but interaction with Fru-2,6-P₂ activates the enzyme to stimulate glycolysis and enhance breakdown of glucose.^[1]

Production regulation

The concentration of Fru-2,6-P₂ in cells is controlled through regulation of the synthesis and breakdown by PFK-2/FBPase-2. The primary regulators of this are the hormones insulin, glucagon, and epinephrine which affect the enzyme through phosphorlyation/dephosphorylation reactions. Release of the hormone glucagon triggers production of cyclic adenosine monophosphate (cAMP), which activates a cAMP-dependent protein kinase. This kinase phosphorylates the PFK-2/FBPase-2 enzyme at an NH₂-terminal Ser residue with ATP to activate the FBPase-2 activity and inhibit the PFK-2 activity of the enzyme, thus reducing levels of Fru-2,6-P₂ in the cell. With decreasing amounts of Fru-2,6-P₂, glycolysis becomes inhibited while gluconeogenesis is activated. Insulin triggers the opposite response. As a phosphoprotein phosphatase, insulin dephosphorylates the enzyme, thus activating the PFK-2 and inhibiting the FBPase-2 activities. With additional Fru-2,6-P₂ present, activation of PFK-1 occurs to stimulate glycolysis while inhibiting gluconeogenesis.^[3]^[5]

Regulation of sucrose production

Fru-2,6-P₂ plays an important role in the regulation of triose phosphates, the end products of the Calvin Cycle. In the Calvin Cycle, 5/6th of triose phosphates are recycled to make ribulose 1,5-bisphosphate. The remaining 1/6 of triose phosphate can be converted into sucrose or stored as starch. Fru-2,6-P₂ inhibits production of fructose 6-phosphate, a necessary element for sucrose synthesis. When the rate of photosynthesis in the light reactions is high, triose phosphates are constantly produced and the production of Fru-2,6-P₂ is inhibited, thus producing sucrose. Fru-2,6-P₂ production is activated when plants are in the dark and photosynthesis and triose phosphates are not produced.^[6]

References

^ ^a ^b Lange AJ. "fructose-2,6-bisphosphate". University of Minnesota.
^ Wu C, Khan SA, Peng LJ, Lange AJ (2006). "Roles for fructose-2,6-bisphosphate in the control of fuel metabolism: beyond its allosteric effects on glycolytic and gluconeogenic enzymes". Adv. Enzyme Regul. 46 (1): 72–88. doi:10.1016/j.advenzreg.2006.01.010. PMID 16860376.
^ ^a ^b Kurland IJ, Pilkis SJ (June 1995). "Covalent control of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: insights into autoregulation of a bifunctional enzyme". Protein Sci. 4 (6): 1023–37. doi:10.1002/pro.5560040601. PMC 2143155. PMID 7549867.
^ KEGG REACTION: R02730
^ Smith WE, Langer S, Wu C, Baltrusch S, Okar DA (June 2007). "Molecular coordination of hepatic glucose metabolism by the 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase:glucokinase complex". Mol. Endocrinol. 21 (6): 1478–87. doi:10.1210/me.2006-0356. PMID 17374851.
^ Nielsen TH, Rung JH, Villadsen D (November 2004). "Fructose-2,6-bisphosphate: a traffic signal in plant metabolism". Trends Plant Sci. 9 (11): 556–63. doi:10.1016/j.tplants.2004.09.004. PMID 15501181.

UpToDate Contents

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2. ホスホフルクトキナーゼ欠損症（糖原病VII型、垂井病） phosphofructokinase deficiency glycogen storage disease vii tarui disease
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5. 腸内ガスと膨満 intestinal gas and bloating

English Journal

Estradiol Stimulates Glucose Metabolism via 6-Phosphofructo-2-kinase (PFKFB3).

Imbert-Fernandez Y1, Clem BF, O'Neal J, Kerr DA, Spaulding R, Lanceta L, Clem AL, Telang S, Chesney J.Author information 1From the James Graham Brown Cancer Center, Division of Medical Oncology and Hematology, Department of Medicine, University of Louisville, Louisville, Kentucky 40202.AbstractEstradiol (E2) administered to estrogen receptor-positive (ER(+)) breast cancer patients stimulates glucose uptake by tumors. Importantly, this E2-induced metabolic flare is predictive of the clinical effectiveness of anti-estrogens and, as a result, downstream metabolic regulators of E2 are expected to have utility as targets for the development of anti-breast cancer agents. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) control glycolytic flux via their product, fructose-2,6-bisphosphate (F26BP), which activates 6-phosphofructo-1-kinase (PFK-1). We postulated that E2 might promote PFKFB3 expression, resulting in increased F26BP and glucose uptake. We demonstrate that PFKFB3 expression is highest in stage III lymph node metastases relative to normal breast tissues and that exposure of human MCF-7 breast cancer cells to E2 causes a rapid increase in [(14)C]glucose uptake and glycolysis that is coincident with an induction of PFKFB3 mRNA (via ER binding to its promoter), protein expression and the intracellular concentration of its product, F26BP. Importantly, selective inhibition of PFKFB3 expression and activity using siRNA or a PFKFB3 inhibitor markedly reduces the E2-mediated increase in F26BP, [(14)C]glucose uptake, and glycolysis. Furthermore, co-treatment of MCF-7 cells with the PFKFB3 inhibitor and the anti-estrogen ICI 182,780 synergistically induces apoptotic cell death. These findings demonstrate for the first time that the estrogen receptor directly promotes PFKFB3 mRNA transcription which, in turn, is required for the glucose metabolism and survival of breast cancer cells. Importantly, these results provide essential preclinical information that may allow for the ultimate design of combinatorial trials of PFKFB3 antagonists with anti-estrogen therapies in ER(+) stage IV breast cancer patients.
The Journal of biological chemistry.J Biol Chem.2014 Mar 28;289(13):9440-8. doi: 10.1074/jbc.M113.529990. Epub 2014 Feb 10.
Estradiol (E2) administered to estrogen receptor-positive (ER(+)) breast cancer patients stimulates glucose uptake by tumors. Importantly, this E2-induced metabolic flare is predictive of the clinical effectiveness of anti-estrogens and, as a result, downstream metabolic regulators of E2 are expecte
PMID 24515104

Central Cavity of Fructose-1,6-bisphosphatase and the Evolution of AMP/Fructose 2,6-bisphosphate Synergism in Eukaryotic Organisms.

Gao Y1, Shen L, Honzatko RB.Author information 1From the Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011.AbstractThe effects of AMP and fructose 2,6-bisphosphate (Fru-2,6-P2) on porcine fructose-1,6-bisphosphatase (pFBPase) and Escherichia coli FBPase (eFBPase) differ in three respects. AMP/Fru-2,6-P2 synergism in pFBPase is absent in eFBPase. Fru-2,6-P2 induces a 13° subunit pair rotation in pFBPase but no rotation in eFBPase. Hydrophilic side chains in eFBPase occupy what otherwise would be a central aqueous cavity observed in pFBPase. Explored here is the linkage of AMP/Fru-2,6-P2 synergism to the central cavity and the evolution of synergism in FBPases. The single mutation Ser(45) → His substantially fills the central cavity of pFBPase, and the triple mutation Ser(45) → His, Thr(46) → Arg, and Leu(186) → Tyr replaces porcine with E. coli type side chains. Both single and triple mutations significantly reduce synergism while retaining other wild-type kinetic properties. Similar to the effect of Fru-2,6-P2 on eFBPase, the triple mutant of pFBPase with bound Fru-2,6-P2 exhibits only a 2° subunit pair rotation as opposed to the 13° rotation exhibited by the Fru-2,6-P2 complex of wild-type pFBPase. The side chain at position 45 is small in all available eukaryotic FBPases but large and hydrophilic in bacterial FBPases, similar to eFBPase. Sequence information indicates the likelihood of synergism in the FBPase from Leptospira interrogans (lFBPase), and indeed recombinant lFBPase exhibits AMP/Fru-2,6-P2 synergism. Unexpectedly, however, AMP also enhances Fru-6-P binding to lFBPase. Taken together, these observations suggest the evolution of AMP/Fru-2,6-P2 synergism in eukaryotic FBPases from an ancestral FBPase having a central aqueous cavity and exhibiting synergistic feedback inhibition by AMP and Fru-6-P.
The Journal of biological chemistry.J Biol Chem.2014 Mar 21;289(12):8450-61. doi: 10.1074/jbc.M114.548586. Epub 2014 Jan 16.
The effects of AMP and fructose 2,6-bisphosphate (Fru-2,6-P2) on porcine fructose-1,6-bisphosphatase (pFBPase) and Escherichia coli FBPase (eFBPase) differ in three respects. AMP/Fru-2,6-P2 synergism in pFBPase is absent in eFBPase. Fru-2,6-P2 induces a 13° subunit pair rotation in pFBPase but no r
PMID 24436333

Japanese Journal

Role of glucose-6-phosphate and xylulose-5-phosphate in the regulation of glucose-stimulated gene expression in the pancreatic β cell line, INS-1E

, , ,
Endocrine Journal 60(4), 473-482, 2013
… Whether glucose-6-phosphate (G6P) or xylulose-5-phosphate (X5P) is the signaling molecule for carbohydrate response element binding protein (ChREBP) transactivation has been controversial. … In this study, we tested the role of G6P and X5P in the regulation of ChREBP transactivation in the pancreatic β cell line, INS-1E. …
NAID 130004443881

Modulation of Allosteric Regulation by E38K and G101N Mutations in the Potato Tuber ADP-glucose Pyrophosphorylase

, , [他], , , , , ,
Bioscience, Biotechnology, and Biochemistry 77(9), 1854-1859, 2013
… Moreover, the enzyme activities of PLS-E38K, PLS-G101N, and PLS-E38K/G101N were more readily stimulated by other major phosphate-ester metabolites, such as fructose 6-phosphate, fructose 2,6-bisphosphate, and ribose 5-phosphate, than was that of PLS-WT. …
NAID 130003361219

Related Pictures

Role of fructose 2,6-bisphosphate in the Fructose 2,6-bisphosphate (FBP-2) Fructose 2 6 Bisphosphate by fructose 2,6-bisphosphate (F2,6BP Regulation of fructose 2,6-bisphosphate HERE Fructose 2,6 Bisphosphate Synthesis Fructose 2,6-bisphosphate; FRUCTOSE-2,6

★リンクテーブル★

リンク元	「フルクトース-2,6-ビスリン酸」
関連記事	「bisphosphate」「fructose」

「フルクトース-2,6-ビスリン酸」

Fructose 2,6-bisphosphate
Identifiers
CAS Registry Number	79082-92-1
ChEBI	CHEBI:28602
ChemSpider	21106440
	InChI InChI=1S/C7H16O12P2/c8-2-7(3-18-21(14,15)16)6(10)5(9)4(19-7)1-17-20(11,12)13/h4-6,8-10H,1-3H2,(H2,11,12,13)(H2,14,15,16)/t4-,5-,6+,7+/m1/s1 ; Key: NSKBXJZGSYZROA-JWXFUTCRSA-N ; InChI=1/C7H16O12P2/c8-2-7(3-18-21(14,15)16)6(10)5(9)4(19-7)1-17-20(11,12)13/h4-6,8-10H,1-3H2,(H2,11,12,13)(H2,14,15,16)/t4-,5-,6+,7+/m1/s1; Key: NSKBXJZGSYZROA-JWXFUTCRBS ;
Jmol-3D images	Image
MeSH	fructose+2,6-bisphosphate
PubChem	105021
	SMILES O=P(O)(O)OC[C@H]1O[C@@](CO)(COP(O)(O)=O)[C@@H](O)[C@@H]1O ;
Properties
Chemical formula	C6H14O12P2
Molar mass	340.116 g/mol
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references

　　[★]

英: fructose-2,6-bisphosphate

「bisphosphate」

　　[★]

二リン酸エステル、二リン酸

関: diphosphate、diphosphoric acid、pyrophosphate

「fructose」

　　[★] フルクトース、果糖、fruit sugar、levulose 　　

[umn-1] Lange AJ. "fructose-2,6-bisphosphate". University of Minnesota.

[pmid16860376-2] Wu C, Khan SA, Peng LJ, Lange AJ (2006). "Roles for fructose-2,6-bisphosphate in the control of fuel metabolism: beyond its allosteric effects on glycolytic and gluconeogenic enzymes". Adv. Enzyme Regul. 46 (1): 72–88. doi:10.1016/j.advenzreg.2006.01.010. PMID 16860376.

[kurland-3] Kurland IJ, Pilkis SJ (June 1995). "Covalent control of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: insights into autoregulation of a bifunctional enzyme". Protein Sci. 4 (6): 1023–37. doi:10.1002/pro.5560040601. PMC 2143155. PMID 7549867.

[4] KEGG REACTION: R02730

[pmid17374851-5] Smith WE, Langer S, Wu C, Baltrusch S, Okar DA (June 2007). "Molecular coordination of hepatic glucose metabolism by the 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase:glucokinase complex". Mol. Endocrinol. 21 (6): 1478–87. doi:10.1210/me.2006-0356. PMID 17374851.

[pmid15501181-6] Nielsen TH, Rung JH, Villadsen D (November 2004). "Fructose-2,6-bisphosphate: a traffic signal in plant metabolism". Trends Plant Sci. 9 (11): 556–63. doi:10.1016/j.tplants.2004.09.004. PMID 15501181.

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fructose-2,6-bisphosphate