Fructose 2,6-bisphosphate
- F-2 ,6 -BP
- Fructose -2 ,6-diphosphate
Fixed
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Fructose -2 ,6 -bisphosphate (F-2 ,6 -BP ) is a doubly phosphorylated sugar ( fructose), which plays in the regulation of glycolysis and gluconeogenesis an important role by the activity of the enzymes phosphofructokinase ( PFK1 ) and fructose -1,6- bisphosphatase ( FBPase1 ) allosterically controlled.
Formation and decomposition
F-2 ,6 -BP is formed from fructose 6 -phosphate, which catalyzes the phosphofructokinase -2 ( PFK -2). This ATP is consumed. The degradation of F-2 ,6 -BP to fructose -6-phosphate and inorganic phosphorus catalyzes the fructose -2 ,6- bisphosphatase ( FBPase -2). Although PFK -2 and FBPase -2 have different enzymatic activities, but together form a bifunctional hormone regulatable enzyme PFKFB.
Effect in glucose metabolism
High physiological concentrations ( in the range of > 0.1 uM ) F-2 ,6 -BP is an effective allosteric activator of phosphofructokinase 1 it also can the blocking effect of the allosteric inhibitor ATP and citrate annulled. Thereby, the key reaction in glycolysis, which highly exergonic phosphorylation of fructose -6-phosphate to fructose -1 ,6- bisphosphate (F-1 ,6 -BP), is activated. It goes without F- 2 ,6 -BP as in conventional almost physiological concentrations of the substrates. By activating the entire glycolysis is stimulated. The product of F-1 ,6- BP that is an activator of the pyruvate kinase, which catalyzes a secondary reaction of glycolysis. This regulatory mechanism is called feedforward stimulation.
The competition reaction for glycolysis, gluconeogenesis, is effectively suppressed by the other hand, high Q -2 ,6 -BP concentrations by the enzyme fructose-1 ,6- bisphosphatase is inhibited allosterically. Through this reciprocal control prevents energy is wasted by the simultaneous expiration of both metabolic pathways.
Regulation of the concentration
If blood sugar levels are low, such as in fasting, is produced in the pancreas, the hormone glucagon. In the liver, the major organ for gluconeogenesis glucagon releases a signaling cascade by which the intracellular cAMP concentration is increased. This activates the cAMP -dependent protein kinase A (PKA), which phosphorylates the PFKFB.
Thus, the PFK2 function is disabled and the FBPase2 of the bifunctional enzyme activated. Consequently, the concentration of fructose -2 ,6- bisphosphate is reduced because it is hydrolyzed by FBPase2 to fructose-6 -phosphate. The Gluconeogeneseenzym FBPase1 is no longer inhibited by the F- 2 ,6- BP and the blood sugar rise. And because at the same time eliminates the stimulatory effect of F-2 ,6- BP on glycolysis.
Conversely, results from high glucose levels through the first steps of glycolysis much fructose 6 -phosphate. This acts as an activator of Phosphoproteinphosphatase, which dephosphorylated PFKFB. Characterized the FBPase2 activity is made off and the PFK2 function and consequently increased phosphorylated F-6- P to F-2 ,6 -BP. This causes an activation of glycolysis and inhibition of gluconeogenesis and thus lowering blood sugar.