Fructose-2,6-bisphosphate

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Structural formula
Structural formula of fructose-2,6-bisphosphate
β- D- fructose-2,6-bisphosphate
General
Surname Fructose-2,6-bisphosphate
other names
  • F-2,6-BP
  • Fructose-2,6-diphosphate
Molecular formula C 6 H 14 O 12 P 2
External identifiers / databases
CAS number 79082-92-1
PubChem 105021
Wikidata Q417484
properties
Molar mass 340.12 g mol −1
Physical state

firmly

safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fructose-2,6-bisphosphate (F-2,6-BP) is a two-fold phosphorylated sugar ( fructose ) that plays an important role in the regulation of glycolysis and gluconeogenesis by increasing the activity of the enzymes phosphofructokinase (PFK1) and fructose -1,6-bisphosphatase (FBPase1) controlled allosterically .

Education and dismantling

Formation and breakdown of fructose-2,6-bisphosphate.

F-2,6-BP is formed from fructose-6-phosphate , which catalyzes phosphofructokinase-2 (PFK-2). Here is ATP consumed. The breakdown of F-2,6-BP to fructose-6-phosphate and inorganic phosphate catalyzes the fructose-2,6-bisphosphatase (FBPase-2). PFK-2 and FBPase-2 have different enzymatic activities, but together they form a bifunctional , hormonally regulated enzyme, the PFKFB .

Effect on glucose metabolism

At a high physiological concentration (in the range of> 0.1 μM), F-2,6-BP is an effective allosteric activator of phosphofructokinase 1. It is also able to neutralize the blocking effect of the allosteric inhibitors ATP and citrate . This activates the key reaction of glycolysis, the highly exergonic phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate (F-1,6-BP). Without F-2,6-BP, it almost does not take place at the usual physiological concentrations of the substrates. Activation stimulates all of the glycolysis. The product F-1,6-BP is namely an activator of pyruvate kinase , which catalyzes a subsequent reaction of glycolysis. This regulation mechanism is called feedforward stimulation.

On the other hand, the competitive reaction to glycolysis, gluconeogenesis, is effectively suppressed by high F-2,6-BP concentrations by allosterically inhibiting the enzyme fructose-1,6-bisphosphatase . This reciprocal control prevents energy from being wasted due to the simultaneous running of both metabolic pathways.

Regulation of concentration

If the blood sugar level is low, e.g. B. in the case of food abstinence, the hormone glucagon is formed in the pancreas . In the liver , the main organ responsible for gluconeogenesis, glucagon triggers a signal cascade that increases the intracellular cAMP concentration. This activates the cAMP-dependent protein kinase A (PKA), which phosphorylates the PFKFB.

This deactivates the PFK2 function and activates the FBPase2 of the bifunctional enzyme. Consequently, the concentration of fructose-2,6-bisphosphate decreases because it 6-phosphate fructose by FBPase2 to hydrolyzed is. The gluconeogenic enzyme FBPase1 is no longer inhibited by F-2,6-BP and blood sugar increases. Also because at the same time the stimulating effect of F-2,6-BP on glycolysis is absent.

Conversely, when the glucose level is high, the first steps of glycolysis produce a lot of fructose-6-phosphate. This acts as an activator of phosphoprotein phosphatase , which dephosphorylates PFKFB. As a result, the FBPase2 activity is turned off and the PFK2 function turned on and consequently more F-6-P is phosphorylated to F-2,6-BP. This causes activation of glycolysis and inhibition of gluconeogenesis and thus a reduction in blood sugar.

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ Wu, C. et al. (2006): Roles for fructose-2,6-bisphosphate in the control of fuel metabolism: beyond its allosteric effects on glycolytic and gluconeogenic enzymes . In: Adv. Enzyme Regul 46 (1); 72-88; PMID 16860376 ; doi: 10.1016 / j.advenzreg.2006.01.010
  3. ↑ a b Kurland, IJ. and Pilkis, SJ. (1995): Covalent control of 6-phosphofructo-2-kinase / fructose-2,6-bisphosphatase: insights into autoregulation of a bifunctional enzyme . In: Protein Sci. 4 (6); 1023-1037; PMID 7549867 ; PMC 2143155 (free full text, PDF).
  4. ↑ a b Hers, HG. and van Schaftingen, E. (1982): Fructose 2,6-bisphosphate 2 years after its discovery . In: Biochem J 206 (1); 1-12; PMID 6289809 ; PMC 1158542 (free full text, PDF).
  5. ↑ Bali, M. and Thomas, SR. (2001): A modeling study of feedforward activation in human erythrocyte glycolysis . In: CR Acad Sci III 324 (3); 185-199; PMID 11291305 ; doi: 10.1016 / S0764-4469 (00) 01295-6 .

literature

  • JM Berg, JL Tymoczko, L. Stryer: Stryer Biochemistry . 6th edition. Spektrum Akademischer Verlag, Munich 2007, ISBN 978-3-8274-1800-5 .
  • David L. Nelson and Michael M. Cox: Lehninger Principles of Biochemistry . Palgrave Macmillan; 5th edition 2008; ISBN 978-0-7167-7108-1 ; P. 587ff.