Glycogen Synthase Kinase 3 (GSK3) and Glycogen Synthase (GS) - the phosphorylation equilibrium

This one causes students problems every year - the relationship between Glycogen Synthase Kinase 3 (GSK3) and Glycogen Synthase (GS), and their phosphorylation states and activity.

If you look at insulin signalling overall:

You will see that activated protein kinase B (activated by phosphorylation) phosphorylates and inactivates GSK3. This means that GSK3 can no longer phosphorylate its substrate, GS.

Now, GS, when phosphorylated, is inactive. Hence, as GSK3 is no longer active (as it is phosphorylated) it cannot phosphorylate GS and inactivate it, therefore GS remains un-phosphorylated and therefore active so it can make glycogen.

The key to understanding this is that phosphorylated (inactive) and un-phosphorylated (active) forms of GS are in a state of equilibrium and that the kinase, GSK3, drives the equilibrium to the right (inactive) in the figure below, whereas the phosphatase (which removes the phosphate) drives the equilibrium to the left (active). Therefore, if you inhibit the action of the kinase (GSK3) the net result is more un-phosphorylated GS, hence more glycogen is made, which is just what we want…

One key thing to keep in mind is that the phosphorylation of a protein can cause it to become active or inactive. It all depends on the protein.

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Additional Resources

• 📗 - Biochemistry (Stryer) (affiliate link)
• 📗 - Principles of Biochemistry (Lehninger) (affiliate link)

What is a Unit of enzyme?

What is a 'Unit' of enzyme.... this always seems to give problems.

1 Unit of enzyme is defined as "an amount of protein that produces 1 µmole of product per minute". The thing that causes the problem is the word "amount".

The "amount" is not a mass; it is, for want of a better word, a 'blob'. You can buy enzymes in 'Units'. You buy a vial that will contain a number of Units of enzyme. You then know that if you dissolve the contents of the vial in a solution, how many µmoles of product per minute will be produced. If you buy 1 Unit of a particular enzyme from two different suppliers you may have vials that contain different weights of powder, but the work that can be done (i.e. the amount of product produced) will be the same.

For example:

Look at these two 'piles' ('blobs') of enzyme:

Pile 1 of Enzyme

Pile 2 of Enzyme

Both 'piles' contain the same number of red balls (i.e. 4), and if 4 red balls are needed to produce 1 µmole of product per minute (i.e. 1 Unit), then both piles can be said to contain 1 Unit of the enzyme, and yet, as you can see, there are many more balls in pile 2... Pile 1 is certainly more pure as there is less contaminant (yellow balls) around.

This is why the 'amount' in "an amount of protein that produces 1 µmole of product per minute" is not a weight; it is an 'amount'; it is a 'pile', a 'blob'.

If you have problems with 'Sciences Maths' then you might like to check out some of the courses over at Maths4Biosciences.

If you would like to support my blogging efforts, then please feel free to buy me a coffee at https://www.buymeacoffee.com/drnickm

Additional Resources

• 📗 - Biochemistry (Stryer) (affiliate link)
• 📗 - Principles of Biochemistry (Lehninger) (affiliate link)