Sunday, October 1, 2023

Glycogenesis & Glycogenolysis

Glycogenesis & Glycogenolysis 

Glycogenesis

Introduction

Glycogenesis can be defined as the process through which glycogen is synthesised and glucose molecules are added to the glycogen chains for storage purposes. In the human body, the process of glycogenesis is activated post the Cori cycle when the body is in a rest period. The process usually occurs in the liver. It is important to note that the process of glycogenesis can also be activated by the peptide hormone insulin in order to respond to relatively high glucose levels in the body.

The biological mechanism of producing glycogen from glucose (which is the simplest cellular sugar) is generally referred to as glycogenesis. Via the glycogenesis phase, the body is known to generate glycogen in order to preserve these molecules for later use (for a time when the body does not have glucose readily accessible). 

It is important to note that glycogen is not the same as fat that is processed for energy in the long term. It is not uncommon for glycogen stores to be used by the body during meals, especially when the concentration of blood glucose has decreased. In this situation, the body’s cells are known to resort to their glycogen reserves, undergoing a process that is the reverse of glycogenesis. This reverse process is generally referred to as glycogenolysis.

Process of Glycogenesis

It is important for the cell to have an excess of glucose in order to commence the process of glycogenesis. Glucose is known to be the starting molecule for the glycogenesis process. The process of glycogenesis is known to begin when a signal from the body to commence glycogenesis is received by cell. It is important to note that these signals could come from a variety of different routes.

Initially, in the process of glycogenesis, the glucose molecule is known to interact with the glucokinase enzyme (which is an enzyme that adds to the glucose a group of phosphates). The phosphate group is moved to the other side of the molecule, with the help of the enzyme phosphoglucomutase, in the next step of the glycogenesis process. 

UDP-glucose pyrophosphorylase, which is another enzyme that is involved in this process, takes this molecule and produces glucose uracil-diphosphate. There are two phosphate groups in this glucose form, along with the nucleic acid uracil. Such additions help to build a chain of molecules, which is vital for the next step of the glycogenesis process.

In the final stage of the glycogenesis process, a very important enzyme known as glycogenin plays a vital role. By attaching itself to this specific molecule, the UDP-diphosphate glucose tends to form relatively short chains. More enzymes facilitate the completion of the process after approximately eight of these molecules form a chain together.

This chain is then added to glycogen synthase. Simultaneously, the enzyme responsible for glycogen branching helps to build branches in the chains. This results in a fairly compact macromolecule that is quite efficient in storing energy.

Regulation of Glycogenesis

Via the process of phosphorylation, glycogen phosphorylase is known to be activated while glycogen synthase is known to be inhibited. Glycogen phosphorylase is generally transformed by the enzyme known as phosphorylase kinase from its relatively less reactive “b” form to a relatively more reactive “a” form. Phosphorylase kinase is also known to be activated by the protein kinase A. Furthermore, phosphoprotein phosphatase-1 is known to be deactivated by the same protein.

The hormone adrenaline acts to stimulate the protein kinase A. Furthermore, the hormone epinephrine binds itself to an adenylate cyclase-activating receptor protein. This enzyme also allows ATP to form cyclic AMP. Two cyclic AMP molecules tend to bind to the kinase A regulatory subunit, which activates it. This allows the protein kinase A catalytic subunit to dissociate from the assembly and to subject other proteins to phosphorylation.

Not only does epinephrine activate glycogen phosphorylase, it also contributes towards the inhibition of glycogen synthase. The effect of activating glycogen phosphorylase is amplified by this. A similar mechanism accomplishes this inhibition. This occurs as the protein kinase A acts to subject the enzyme to phosphorylation (which decreases its activity). This is commonly referred to as coordinate reciprocal control. 

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Glycogenolysis

Introduction 

Animals store glucose as glycogen, which is broken down in a process called glycogenolysis. Glycogenolysis is a metabolic process that converts glycogen from the muscles and liver to its monosaccharide form, glucose. Glycogen is a glucose polysaccharide stored in the muscles and liver. The body utilises this to produce ATP (adenosine triphosphate), an organic substance that provides energy to drive various activities in living cells.

Low levels of ATP within live cells trigger the glycogenolysis process. When the cells detect a low level of ATP, the liver and muscles liberate glycogen and break it down into glucose or simple sugars, which are then used to produce ATP.

Thus, glycogen (n) is broken down into glucose-1-phosphate and glycogen (n-1) during glycogenolysis.

Location

Glycogenolysis occurs in the cytoplasm of cells in the liver, muscles, and adipose tissue.

The liver breaks down the glycogen to maintain the glucose level in the blood. The muscle cells break down the glycogen to conserve the energy required for the contraction of muscles.

Steps or Mechanisms

1.Glycogen phosphorylase and phosphorylase kinase, activated by phosphorylation, are the two main regulating enzymes of glycogenolysis. These will primarily be expressed in the brain, muscles, and liver.

2.Adenyl cyclase and cAMP activity in the muscle triggers the beginning of glycogenolysis. After phosphorylase kinase is bound by cAMP and transformed into its active state, phosphorylase b is changed into phosphorylase a, which ultimately catalyses glycogen degradation.

3.Glycogenolysis can occur either in the lysosomes or in the cytosol. The cytosolic enzyme glycogen phosphorylase uses inorganic phosphate to cleave α-1,4 bonds to catalyse the production of glucose-1-phosphate from the terminals of glycogen branches.

4.The enzyme phosphoglucomutase converts glucose-1-phosphate into glucose-6-phosphate, which frequently ends in glycolysis.

5.Acid α-glucosidase, an enzyme in the lysosome, uses an autophagy-dependent mechanism to break down lysosomal glycogen. This mechanism acts as an instant source of energy during the newborn stage.

6.When glycogen phosphorylase enzyme reaches a branch point that is four glucose residues away from it, it transfers one of the branches to another chain, generating a new α-1,4 bond and leaving one glucose unit at the branch site later hydrolysed by α-1,6-glucosidase to produce free glucose. This occurs because the phosphorylase enzyme can only cleave until it is four units from the branch point.

7.The general reaction for the conversion of glycogen to glucose-1-phosphate is:

Glycogen(n residues) + Pi ⇌ Glycogen(n-1 residues) + Glucose-1-phosphate

Enzymes

The important enzymes involved in the process of glycogenolysis include glycogen phosphorylase, phosphorylase kinase, and phosphoglucomutase.

In the muscle cells, adenyl cyclase and cAMP bind to and activate the enzyme phosphorylase kinase and transform phosphorylase b into phosphorylase a, which catalyses the glycogen breakdown.

Glycogen is broken down into glucose-1-phosphate and glucose-6-phosphate in the cytosol by glycogen phosphorylase.

Phosphoglucomutase converts glucose-1-phosphate (reversibly) into glucose-6-phosphate in the liver, kidney, and intestines.

Functions and Significance

The liver and muscle tissue cells undergo glycogenolysis in response to neurological and hormonal impulses. Glycogenolysis, in particular, is crucial for controlling blood glucose levels and the fight-or-flight response.

Glycogen breakdown in the muscle cells (myocytes) serves as an instant resource of glucose-6-phosphate for the process of glycolysis, which produces energy for muscle contraction.

The process of glycogenolysis differs in liver cells or hepatocytes. The liver does not immediately utilise the glucose that is created during glycogenolysis in the liver. Instead, glucose travels via the bloodstream to be utilised by other cells.

Glycogen is a form of energy storage in animals similar to starch, and a form of energy storage in plants that may be degraded when a plant requires energy.

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