Fructose 2,6-bisphosphate

Fructose 2,6-bisphosphate

Haworth projection of α-D-fructose-2,6-bisphosphate.
Identifiers
CAS Number	79082-92-1 Y
3D model (Jmol)	Interactive image
ChEBI	CHEBI:28602 N
ChemSpider	21106440 Y
MeSH	fructose+2,6-bisphosphate
PubChem CID	105021
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 Y Key: NSKBXJZGSYZROA-JWXFUTCRSA-N Y 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
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).
N  (what is YN ?)
Infobox references

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 a bifunctional enzyme containing both PFK-2 and FBPase-2, which is dephosphorylated, allowing the PFK-2 portion to phosphorylate fructose 6-phosphate using ATP. The breakdown of Fru-2,6-P₂ is catalyzed by the phosphorylation of the bifunctional enzyme, which allows FBPase-2 to dephosphorylate Fructose-2,6-bisphosphate to produce Fructose 6-phosphate and P_i.

Reaction scheme of breakdown of fructose-2,6-bisphosphate to fructose-6-phosphate.

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.