|Jmol-3D images||Image 1|
|Molar mass||340.116 g/mol|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
|(what is: / ?)|
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. Fru-2,6-P2 is synthesized and broken down by the bifunctional enzyme phosphofructokinase 2/fructose-2,6-bisphosphatase (PFK-2/FBPase-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 Pi.
Reaction scheme of breakdown of fructose 2,6-bisphosphate to fructose 6-phosphate.
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.
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.
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.
- 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.
- 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.