I. What is Glycogenesis?
If you know what glucose is and you’ve read the first book of the bible, then you probably already pieced together what the word means! The ability to store glucose is essential for a cell in order to acquire a quick source of glucose for oxidation and therefore energy!
A great way to approach and review this article is to compare and contrast it with its counter article discussing glycogenolysis! We’re big proponents of tackling “partner” topics because you can almost kill 2 birds with one stone!
Though the title refers to glycogenesis, we’ll also first cover the basics in terms of the definition, structure, and function of glycogen in order for you all to first understand the underlying principles and importance of glycogen before talking about the processes.
II. Metabolism of Glycogen | Glycogenesis
As mentioned above, let’s first cover the basics of glycogen, specifically briefly talking about its structure and its function within the cell.
A. Glycogen Overview
Glycogen is a polymer storage molecule composed of repeating glucose monomers, which are placed in granules located within the cytoplasm.
I. Structure
In a more detailed sense, these glucose monomers are connected in either a linear (𝛼-1,4 glycosidic bond) or branched fashion (𝛼-1,6 glycosidic bond), with each linear chain attached to a central protein called glycogenin.
The numbers preceding the name just refer to the carbons that are connected via the bond. Recall that carbons on glucose are numbered from 1 to 6, with the anomeric carbon being labeled C1.
II. Function
As mentioned, glycogen is utilized as an glucose storage within the cell so as to quickly access glucose for energy. But what is the point of having branching chains in addition to the linear chain?
An important idea to note is that when glucose is needed from glycogen, a single monomer is broken from the END of the chain, not in the middle!
If only linear chains were present, glycogen could only release glucose from 1 terminal end. The presence of branching increases the surface area and end points where glycogen can release glucose and increases the rate of glycogen breakdown!
In addition, the increased branching also increases the SOLUBILITY of glycogen, which helps as it’s located in cytoplasm which is composed of predominantly water!
B. Glycogenesis
For glycogenesis, we’ll divide the process into 2 portions: 1) extension of the linear chain and 2) branching of the linear chain.
I. Extension of Linear Chain
To extend the linear chain via an 𝛼-1,4 glycosidic bond, an incoming glucose-6-phosphate is isomerized to glucose-1-phosphate via phosphoglucomutase.
Be wary not to confuse this with glucose-6-phosphate isomerase as this enzyme catalyzes the isomerization to fructose-6-phosphate in glycolysis.
The isomerized glucose-1-phosphate is then “activated” by the attachment of a uridine diphosphate group via an enzyme called uridyltransferase which produces UDP-glucose, while also releasing a pyrophosphate.
The UDP-glucose molecule can now be linearly added to the glycogen chain forming the 𝛼-1,4 glycosidic bond via glycogen synthase, the rate limiting enzyme of glycogenesis.
II. Branching of Linear Chain
Luckily, there’s only one enzyme to memorize that’s involved in the formation of 𝛼-1,6 glycosidic bonds and branching of the linear chain, conveniently named the branching enzyme! There are 2 main steps involved in forming the branches:
The branching enzyme first hydrolyzes an 𝛼-1,4 glycosidic bond, releasing a short glycogen oligomer (a short polymer chain).
The glycogen oligomer is then repositioned to where the branching enzyme can catalyze the synthesis of an 𝛼-1,6 glycosidic bond.
III. Bridge/Overlap
The best way to study and understand glycogenesis is to put it into context to how it’s physiologically important for the functioning of the body, especially via hormones! Let’s take a look at hormonal regulation!
I. Hormonal Regulation
Recall that insulin is a peptide hormone released by the pancreatic 𝛽-islet cells which promotes the decrease of blood glucose via glucose transport into the cell.
As such, it should come at no surprise that insulin also promotes an increase in glycogenesis, specifically by stimulating the activity of glycogen synthase.
This makes sense when looking at the function of insulin: one method to increase glucose uptake by a cell would be to store that glucose within the cell; in this case, via the form of glycogen!
IV. Wrap Up/Key Terms
Let’s take this time to wrap up & concisely summarize what we covered above in the article!
A. Glycogen Overview
Glycogen is a type of storage polymer composed of repeating glucose molecules; they are arranged in granules which are localized in the cytoplasm.
I. Structure
Glycogen can be further described as having both a linear (𝛼-1,4 glycosidic bond) and branching (𝛼-1,6 glycosidic bond); the linear chains are attached to a central glycogenin protein while the branches “branch off” from the linear chains.
II. Function
By serving as a storage for glucose, the cell can catalyze the release of glucose from glycogen to be used as a means for energy via glucose oxidation.
The presence of branched contains has 2 major functions: 1) allows for a quicker breakdown of glycogen to glucose via increased glycogen surface area and terminal ends and 2) increases the solubility of glycogen in the cytoplasm.
B. Glycogenesis
We’ll break down glycogenesis into the following stages: 1) extension of the linear chain and 2) branching of the linear chain!
I. Extension of Linear Chain
A glucose-6-phosphate is isomerized to glucose-1-phosphate via the enzyme phosphoglucomutase. G1P is then “activated” via the addition of a UDP molecule originating from a UTP through the enzyme uridyltransferase.
Glycogen synthase, the rate limiting enzyme, can finally catalyze the formation of an 𝛼-1,4 glycosidic bond to extent the glycogen linear chain!
II. Branching of Linear Chain
The branching process is catalyzed completely by the branching enzyme! First, the branching enzyme hydrolyzes an 𝛼-1,4 glycosidic bond, releasing a short chain glycogen oligomer.
The short chain glycogen oligomer is then repositioned to allow for the generation of an 𝛼-1,6 glycosidic bond, creating the branch!
V. Practice
Take a look at these practice questions to see and solidify your understanding!
Sample Practice Question 1
Which of the following enzymes involved in glycogenesis is most likely subjected to heavy allosteric regulation?
A. Glycogen Synthase
B. Phosphoglucomutase
C. Uridyltransferase
D. Branching Enzyme
Ans. A
Out of all the enzymes, glycogen synthase is most likely to be subjected to heavy allosteric regulation as it is the rate limiting enzyme of glycogenesis!
This is similar to how phosphofructokinase-1 and isocitrate dehydrogenase are also enzymes subject to strict regulation as they are also the rate limiting enzymes in their respective processes.
Sample Practice Question 2
The bronchioles of the lungs further extend into the alveoli which organize in a way to increase the surface area of gas exchange with the blood. This is most analogous to which of the following?
A. Branched Glycogen Chains
B. Linear Glycogen Chains
C. Glycogen Synthase
D. UDP Addition
Ans. A
Recall that branch chains are important for increasing the surface area of glycogen, specifically increasing the number of terminal ends that can catalyze glucose release. This is similar to how alveoli is arranged to increase surface area of gas exchange!
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