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C) For each of these reactions, name the key enzyme that bypasses that step during gluconeogenesis. Glycolysis Reaction # GluE) OK, lets go back to the first of those glycolysis steps that you said was highly regulated. Using THERMODYNAMICS terms, w

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According to the given question-

We know that the primary role of glucose during metabolism is providing energy, i.e. work as a universal fuel as well as also work as a building block for the microorganism as well as humans.

When the glucose is in excess, it stored in the form of glycogen in the liver and muscle. When the amount of glycogen is depleted, then our body synthesizes glucose from other non-carbohydrate sources, through Gluconeogenesis, which converts pyruvate as well as 3 or 4 carbon compounds into molecules of glucose.

In mammals, the process of Gluconeogenesis occurs mainly in the liver, as well as in the renal cortex, but in small amounts.

During Glycolysis glucose molecule is broken down into pyruvate through a series of enzymatic reactions.

Glycolysis and Gluconeogenesis share several steps i.e. out of 10 steps, 7 enzymatic reactions are of Glycolysis is reverse of Gluconeogenesis.

But 3 reactions of Glycolysis are irreversible and not used by Gluconeogenesis –

Such as – formation of glucose 6-phosphate from glucose with the help of enzyme hexokinase, phosphorylation of fructose 6-phosphate into fructose 1,6-bisphosphate with the help of enzyme phosphofructokinase-1, and formation of pyruvate from phosphoenolpyruvate with the help of enzyme pyruvate kinase. These 3 reactions have a large negative free-energy change.

But in gluconeogenesis, these 3 irreversible steps are bypassed with the help of enzymes, and the reactions are exergonic for glucose synthesis.

First bypass reaction –

Pyruvate ----- > Phosphoenolpyruate with the help of enzyme pyruvate carboxylase and PEP carboxylase.

Second bypass reaction

Fructose 1,6-Bisphosphate --- > Fructose 6-Phosphate with the help of enzyme fructose 1,6-bisphosphatase

Third bypass reaction

Glucose 6-Phosphate ---- > Glucose with the help of enzyme glucose 6-phosphatase

Question D-

We know that the Fructose 2,6-Bisphosphate work as a Potent Regulator of both the pathway of Glycolysis as well as Gluconeogenesis.

The liver maintains a   constant level of blood glucose, with the help of regulatory mechanisms Which helps in glucose consumption as well as glucose production.

When the level of glucose in the blood decreases, then glucagon hormone signals the liver to form as well as release more amount of glucose. Glucose is either released from glycogen which is stored in the liver or produced through gluconeogenesis.

The hormonal control of Glycolysis, as well as Gluconeogenesis, is mediated with the help of fructose 2, 6-bisphosphate, which works as an allosteric effector for phosphofructokinase-

A molecule of fructose 2,6-bisphosphate is not found in the pathway of both glycolysis or gluconeogenesis, nor it s an intermediate of both pathway, but the concentration of fructose 2,6-bisphosphate is reflecting the glucagon level in blood.

When glucose level decreases then the level of fructose 2, 6-bisphosphate is increased.

The fructose 2,6-bisphosphate relative concentration in the cell is determined by its breakdown as well as formation. fructose 2,6-bisphosphate   is formed from fructose 6-phosphate by the process of phosphorylation with the help of enzyme phosphofructokinase-2 or PFK-2, and it is broken down by the fructose 2,6-bisphosphatase or FBPase-2.

FBPase-2 and PFK-2 are different enzymatic activities done by a bi-functional protein in the liver, responsible for determining the fructose 2,6-bisphosphate level in the cell, and their level if also controlled by insulin and glucagon.

Glucagon generally stimulates enzyme adenylyl cyclase in the liver to synthesize cAMP or 3,5-cyclic AMP by the breakdown of from ATP. the cAMP is responsible for activating the cAMP-dependent protein kinase, which causes the transfer of a phosphoryl group from ATP to PFK-2/FBPase-2, due to which the FBPase-2 activity is increases and PFK-2 activity is inhibited. So the Glucagon decreases the level of fructose 2,6-bisphosphate inside the cell by promoting the Gluconeogenesis and at the same time inhibiting Glycolysis. This leads to the production of more molecules of glucose and liver replenish glucose in the blood due to response from glucagon.

While Insulin stimulates the phosphoprotein phosphatase activity and removes the phosphoryl group from PFK-2/FBPase-2, due to which PFK-2 activity is increases and the level of, fructose 2,6-bisphosphate is increased by the glycolysis, and same time inhibits the process of gluconeogenesis.

Fructose 2, 6-bisphosphate, allosterically affects phosphofructokinase 1 or PFK-1 as well as fructose 1,6-bisphosphatase or FBPase-1 catalytic activity for the regulation Glycolysis and Gluconeogenesis.

Question E-

Because these steps have very large negative free-energy change, while other steps of Glycolysis have energy close to 0.

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