What is the role of fructose 2 6-Bisphosphate as a regulatory signal?
What is the role of fructose 2 6-Bisphosphate as a regulatory signal?
Fructose-2,6-bisphosphate (F26P2) was identified as a regulator of glucose metabolism over 25 years ago. These coordinated changes in GK and G6Pase protein illustrate how F26P2 regulates glucose metabolism. F26P2 also affects the gene expression of enzymes related to lipid metabolism.
How does fructose 1/6-Bisphosphate regulate glycolysis?
Phosphofructokinase (PFK) utilizes ATP to phosphorylate fructose-6-phosphate to fructose-1,6-bisphosphate. As a regulatory enzyme of glycolysis, PFK is negatively inhibited by ATP and citrate and positively regulated by ADP.
How can fructose 2 6-Bisphosphate help global control to supersede local allosteric control within the cell?
Fructose-2,6-bisphosphate promotes the relaxed state, activating Phosphofructokinase even at high [ATP]. Thus activation by fructose-2,6-bisphosphate, whose concentration fluctuates in response to external hormonal signals, supersedes local control by [ATP].
How does insulin control fructose 2 6-Bisphosphate?
Insulin and dexamethasone both stimulate an increase in the level of PFK-2/FBPase-2 gene expression. This regulation is sensitive to glucose levels or hormones involved in regulating carbohydrate metabolism such as insulin, which stimulates glycolysis, and glucagon, which induces gluconeogenesis.
What controls the synthesis and degradation of fructose 2 6-Bisphosphatase?
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 phosphorylation/dephosphorylation reactions.
Does fructose 2 6-Bisphosphate inhibit glycolysis?
Fructose-2,6-bisphosphate functions as a potent allosteric activator of PFK1, a rate-limiting enzyme of glycolysis. Therefore, TIGAR inhibits glycolysis, thereby redirecting cellular glucose metabolism to the pentose phosphate pathway shunt.
How does fructose 2 6-Bisphosphate activate glycolysis?
Fru-2,6-P2 strongly activates glucose breakdown in glycolysis through allosteric modulation (activation) of phosphofructokinase 1 (PFK-1).
Does fructose 2 6-Bisphosphate inhibit gluconeogenesis?
Also, Fructose-2,6-bisphosphate is an allosteric inhibitor of Fructose-1,6-bisphosphatase and, thus, inhibits gluconeogenesis. When the concentration of Fructose-2,6-bisphosphate drops, glycolysis is no longer activated (becomes inhibited) and gluconeogenesis becomes activated (no longer inhibited).
How glycolysis and gluconeogenesis are regulated by the concentration of fructose 2,6-bisphosphate?
Glucose increases the concentration of fructose-2,6-bisphosphate in vivo, probably by increasing the availability of fructose-6-phosphate, thereby stimulating PFK-2, the kinase for which this is a substrate and inhibiting the phosphatase, FBPase-2. The effect is to increase glycolysis and inhibit gluconeogenesis.