Question

D) Now let's think about the role of fructose 2,6-bisphosphate and the role of glucagon in stimulating liver cells to make and secrete glucose to the blood. in the level of fructose 2,6-bisphosphate. High glucagon would cause a(an) (Write either “increase” or “decrease” in that blank.) What enzyme does fructose 2,6-bisphosphate ACTIVATE? E) OK, let's go back to the first of those glycolysis steps that you said was highly regulated. Using THERMODYNAMICS terms, what is it about this reaction that makes it a good point for regulation?

Answer 1

Answer-

According to the given question-

• Fructose 2,6-Bisphosphate plays an important regulator of the Glycolysis pathway and Gluconeogenesis pathway. The liver plays an important role in maintaining the glucose in the blood at a constant level, through the regulatory mechanisms, for production as well as glucose consumption.
• When the blood glucose level drop below the normal then hormone glucagon gives signals to the liver for production as well as the release of glucose in a higher amount so that the level of glucose can be maintained.
• So the liver causes breakdown the glycogen into glucose or produces glucose through the process of Gluconeogenesis.
• Glycolysis, and Gluconeogenesis both are under the control of hormones to maintain the blood glucose level and are regulated by fructose 2, 6-bisphosphate.
• Fructose 2, 6-bisphosphate is an allosteric effector for enzyme phosphofructokinase. Fructose 2,6-bisphosphate is neither the intermediate of Glycolysis or Gluconeogenesis nor used in both the pathway but their concentration depends upon the blood glucagon level.
• A decrease in blood glucose level leads to an increase in fructose 2, 6-bisphosphate level. Phosphofructokinase-2 or PFK-2 convert fructose 6-phosphate into Fructose 2,6-bisphosphate, while the Fructose 2,6-bisphosphate is broken down with the help of enzyme fructose 2,6-bisphosphatase or FBPase-2.
• Both the FBPase-2 and PFK-2 enzymatic activities are different and are done by a single bi-functional protein found in the liver, which plays an important role in maintaining the level of fructose 2,6-bisphosphate inside the cell, and also under the control of hormone insulin and glucagon.
• Glucagon is responsible for stimulating the adenylyl cyclase enzyme inside the liver and leads to a synthesis of 3,5-cyclic AMP or cAMP from the ATP breakdown.
• cAMP-dependent protein kinase is responsible for the transfer of the phosphoryl group upon activation with cAMP from ATP to PFK-2/FBPase-2 bifunctional protein and leads to an increase in FBPase-2 activity and same time inhibit PFK-2 activity.
• Due to this activity Glucagon causes a decrease in fructose 2,6-bisphosphate level in the cell because this promotes the process of Gluconeogenesis and inhibits Glycolysis. So due to this action more glucose molecules are produced and level of glucose increased in the blood.
• The insulin hormone is responsible for stimulating the phosphoprotein phosphatase activity and leads to the removal of a phosphoryl group from bi-functional protein PFK-2/FBPase-2, and this action causes an increase in PFK-2 activity and fructose 2,6-bisphosphate level increases and this promotes Glycolysis and inhibits Gluconeogenesis.
• So we can say that the hormone Glucagon, lower the fructose 2,6-bisphosphate level inside the cell because it is responsible for inhibiting the process of glycolysis and causes stimulation of gluconeogenesis, because of FBPase-2 activity of a bifunctional protein.

Thus the Blank - Decrease.

• Fructose 2, 6-bisphosphate, is an allosteric regulator of fructose 1,6-bisphosphatase or FBPase-1 and phosphofructokinase 1 or PFK-1, so it allosterically affects the activity of both the enzymes to regulates the pathway of Glycolysis and Gluconeogenesis.

Question E-

• Glycolysis is highly regulated and maintains a constant level of ATP, through the generation of NADH, consumption of ATP and allosteric regulation of enzymes such as hexokinase, Phosphofructokinase-1 or PFK-1, and pyruvate kinase enzyme. Glycolysis is also controlled by hormones such as insulin, glucagon, and epinephrine.
• These steps which are allosterically regulated by three enzymes have a large negative free-energy change, compared to the remaining steps of Glycolysis, which have energy close to zero.