Question

Overview Gluconeogenesis

1. Differentiate between the fed and fasting state of the body based on glucose obtained from diet, glycogen, and gluconeogenesis (GNG)
2. Define GNG based on precursor molecules
3. Compare GNG and glycolysis based on initial substrates and final products
4. Describe how GNG is not the exact reverse of glycolysis based on irreversible reactions of glycolysis.

Answer 1

ans:)Glycogenesis is the biological process of forming glycogen from glucose, the simplest cellular sugar. The body creates glycogen through the process of glycogenesis to store these molecules for use later, when the body does not have readily available glucose. Glycogen is not the same as fat, which is stored for long term energy. Glycogen stores are often resorted to between meals, when the blood glucose concentration has dropped. In this case, the cells of the body resort to their stores of glycogen, undergoing the reverse process from glycogenesis. This process is called glycogenolysis.

A) diffrenciate between fed and fasting state of body based on glucose obtained from diet glycogen and glycogenesis:

***The fed, or postabsorptive, state in which  we consume and digest an evening meal, glucose and amino acids are transported from the intestine to the blood.

The dietary lipids are packaged into chylomicrons and transported to the blood by the lymphatic system. This fed condition leads to the secretion of insulin, which is one of the two most important regulators of fuel metabolism, the other regulator being glucagon

The secretion of the hormone insulin by the β cells of the pancreas is stimulated by glucose and the parasympathetic nervous system . In essence, insulin signals the fed state—it stimulates the storage of fuels and the synthesis of proteins in a variety of ways.

For instance, insulin initiates protein kinase cascades—it stimulates glycogen synthesis in both muscle and the liver and suppresses gluconeogenesis by the liver. Insulin also accelerates glycolysis in the liver, which in turn increases the synthesis of fatty acids.

The liver helps to limit the amount of glucose in the blood during times of plenty by storing it as glycogen so as to be able to release glucose in times of scarcity.

Insulin accelerates the uptake of blood glucose into the liver by GLUT2. The level of glucose 6-phosphate in the liver rises because only then do the catalytic sites of glucokinase become filled with glucose.

glucokinase is active only when blood-glucose levels are high. Consequently, the liver forms glucose 6-phosphate more rapidly as the blood-glucose level rises. The increase in glucose 6-phosphate coupled with insulin action leads to a buildup of glycogen stores.

The hormonal effects on glycogen synthesis and storage are reinforced by a direct action of glucose itself. Phosphorylase a is a glucose sensor in addition to being the enzyme that cleaves glycogen.

When the glucose level is high, the binding of glucose to phosphorylase a renders the enzyme susceptible to the action of a phosphatase that converts it into phosphorylase b, which does not readily degrade glycogen. Thus, glucose allosterically shifts the glycogen system from a degradative to a synthetic mode.

***  fasting state: The blood-glucose level begins to drop several hours after a meal, leading to a decrease in insulin secretion and a rise in glucagon secretion; glucagon is secreted by the α cells of the pancreas in response to a low blood-sugar level in the fasting state.

Just as insulin signals the fed state, glucagon signals the starved state. It serves to mobilize glycogen stores when there is no dietary intake of glucose.

The main target organ of glucagon is the liver. Glucagon stimulates glycogen breakdown and inhibits glycogen synthesis by triggering the cyclic AMP cascade leading to the phosphorylation and activation of phosphorylase and the inhibition of glycogen synthase .

Glucagon also inhibits fatty acid synthesis by diminishing the production of pyruvate and by lowering the activity of acetyl CoA carboxylase by maintaining it in an unphosphorylated state. In addition, glucagon stimulates gluconeogenesis in the liver and blocks glycolysis.

The large amount of glucose formed by the hydrolysis of glucose 6-phosphate derived from glycogen is then released from the liver into the blood

The entry of glucose into muscle and adipose tissue decreases in response to a low insulin level. The diminished utilization of glucose by muscle and adipose tissue also contributes to the maintenance of the bloodglucose level. The net result of these actions of glucagon is to markedly increase the release of glucose by the liver.

***Define GNG on the based of precausor molecule:

Glycogenesis is the process of storing excess glucose for use by the body at a later time. The glycogen stored by the liver is broken down to glucose and dispersed throughout the body:

To start the process, the cell must have an excess of glucose. Glucose is the starting molecule, and is modified through the process of glycogenesis. Through the modifications, it gains the ability to be stored in long chains.

The process starts when the cell receives a signal from the body to enter glycogenesis. These signals could come from a number of different routes, and are discussed in a later section. When glucose enters the glycogenesis process, it must be acted on by a number of enzymes .

First, the glucose molecule interacts with the enzyme glucokinase, which adds a phosphate group to the glucose. In the next step of glycogenesis, the phosphate group is transferred to the other side of the molecule, using the enzyme phosphoglucomutase. A third enzyme, UDP-glucose pyrophosphorylase, takes this molecule and creates uracil-diphosphate glucose. This form of glucose has two phosphate groups, as well as the nucleic acid uracil. These additions aid in the next step, creating a chain of molecules.

A special enzyme, glycogenin, takes the lead in this part of glycogenesis. The UDP-diphosphate glucose can form short chains by binding to this molecule. After around 8 of these molecules chain together, more enzymes come in to finish the process. Glycogen synthase adds to the chain, while glycogen branching enzyme helps create branches in the chains. This leads to a more compact macromolecule, and thus more efficient storage of energy.

***define glycolysis and glycogenesis on the based of intial substrate and final product:

Glycolysis and gluconeogenesis refer to the breakdown of glucose and the synthesis of new glucose respectively. Both are absolutely essential metabolic processes, as the amount of glucose your body consumes in a day is astronomical in molecular terms.

Glycolysis, which includes 10 reactions in all, starts with the addition of a phosphate group to a glucose molecule. In a series of steps, another phosphate group is added while the molecule is rearranged into a derivative of the sugar fructose. Then, the six-carbon molecule is split into two identical three-carbon molecules.

In the second half of glycolysis, the two identical molecules undergo a series of rearrangements to become the three-carbon molecule pyruvate. Along the way, phosphates are removed from the molecules to create adenosine triphosphate (ATP), which all cells require for energy. Each glucose molecule results in two pyruvate molecules and two ATP.

*Gluconeogenesis has multiple starting points, including the pyruvate cousin lactate. However, the first committed step of the process is the conversion of pyruvate to phosphoenolpyruvic acid, or PEP. This molecule is also an intermediate in glycolysis, when things are proceeding in the opposite direction.

There are three enzymes used in gluconeogenesis that are not used in glycolysis to move the series of reactions as a whole in the opposite direction. The first such reaction has been mentioned, the conversion of pyruvate to PEP. The second is the removal of one phosphate group from a fructose derivative, and the third is the removal of a second phosphate group from glucose-6-phosphate to leave glucose.

The pyruvate entering gluconeogenesis can come from a variety of sources. One of these is the carbon-heavy portion of certain amino acids found in proteins, and another is from the oxidation of fatty acids. This is why foods consisting only or heavily of proteins and fats can serve as fuel sources along with carbohydrates.

***Describe how GNG is not the exact reverse of glycolysis based on irreversible reactions of glycolysis.:

Glycolysis irreversible:The reason for this intricate process is both because the direct conversion of PEP to pyruvate is irreversible and because the cell must avoid a futile cycle in which pyruvate from glycolysis is immediately converted back to PEP

Glycolysis reversed:Gluconeogenesis is much like glycolysis only the process occurs in reverse. However, there are exceptions. In glycolysis there are three highly exergonic steps (steps 1,3,10). These are also regulatory steps which include the enzymes hexokinase, phosphofructokinase, and pyruvate kinase.

This is the reasons that both reactions are not same.

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