Glycogen Metabolism 2 - Online Tutor, Practice Problems & Exam Prep

Glycogen phosphorylase mobilizes glycogen by cleaving glucose subunits as glucose 1-phosphate, which is then converted to glucose 6-phosphate by phosphoglucomutase. This enzyme is activated through phosphorylation, contrasting with glycogen synthase, which is activated when dephosphorylated. High blood glucose increases insulin, reducing glycogen breakdown, while low glucose elevates glucagon, promoting glycogenolysis. The debranching enzyme transfers sugar units from branches, releasing free glucose. This regulation prevents futile cycles in metabolism, ensuring efficient energy mobilization and storage.

Glycogen Metabolism 2

So what happens when we actually need to use some of our glycogen? When we need to mobilize our sugar stores? Well, that's where Glycogen Phosphorylase comes in. This enzyme breaks down glycogen by removing subunits again from the non-reducing end, right? So glycogen synthase works at the non-reducing end. Glycogen phosphorylase also works at the non-reducing end. This isn't the last parallel you're going to see between these two enzymes. What's cool about glycogen phosphorylase is unlike most enzymes we've seen up to this point that cut stuff, right? They cut stuff with water usually like hydrolases. This is a phosphorylase. It cuts stuff with phosphate. So it breaks things by phosphorylysis. It's just a cool, cool thing but it's also important, right? This isn't arbitrary. Actually, it breaks off glucose subunits as glucose 1-phosphate. So they have the phosphate bound to them when they are cut away from glycogen. Why is this important? Well, how is glucose kept in the cell normally? It's immediately converted to glucose 6-phosphate. So the fact that it's coming off with the phosphate group attached is super important.

You might recall from the previous page that the enzyme phosphoglucomutase converts glucose 6-phosphate into glucose 1-phosphate prepping it for glycogen synthase. Well, guess what? It does the same thing in reverse, here taking glucose 1-phosphate and turning it into glucose 6-phosphate. So, you know, this is an isomerase. So it has a delta Δ of around 0. Readily reversible. It can go both ways.

Glucagon, epinephrine, and AMP all stimulate phosphorylase kinase to add two phosphate groups to phosphorylate glycogen phosphorylase. And when glycogen phosphorylase has those two phosphate groups attached, it becomes activated, right? So I just want you to think about something for a second. Glycogen synthase becomes active when it's dephosphorylated. Super important, right? Glycogen synthase becomes activated when it's dephosphorylated whereas glycogen phosphorylase becomes activated when it's phosphorylated. Okay. So the same process for both of these enzymes has an opposite effect. Why do you think this might be important?

Well, let's think back to glycolysis and gluconeogenesis, right? We don't want glycogen phosphorylase and glycogen synthase running simultaneously, right? So if you phosphorylate both or dephosphorylate both, you'll be able to regulate them perfectly because one will turn on, the other will turn off given each condition. Alright. So glucose actually allosterically regulates the enzyme glycogen phosphorylase and it exposes the phosphate groups bound to the enzyme that activate it and it exposes them to make them easier to remove. So it basically makes it easier to shut off glycogen phosphorylase. Now, if you think about this, glycogen phosphorylase breaks down glucose, right? So if you have excess glucose, then that glucose is going to lead to the shutdown of the glycogen phosphorylase. Again, it's just negative feedback, right? Again and again and again and again. Inescapable. It's everywhere in biology.

So, one last note that I want to mention is if you think about it, glycogen has extensive branching, right? That means that there are many non-reducing ends, right? Many available points for glycogen phosphorylase or I should say glycogen phosphorylases, many of them, to attach to and start cutting off glucoses. So that means that very rapidly with the hit of a signal, you can very rapidly produce a ton of glucose and mobilize it for the body. So essentially, many of these enzymes will work simultaneously together to very quickly deliver a ton of glucose to the body. And you can see a model of glycogen phosphorylase working right here and bear in mind that this is all glucose 1-phosphate.

What about the branch points, right? Always what about the branch points? Well, just like there's a branching enzyme, there's also a debranching enzyme. And I know biochemists are not the most creative with their naming schemes but hey, at least when you hear the enzyme name, you already know what it does. Right? So debranching enzyme, will transfer three sugar units from one branch to another. So looking at our figure here, it'll take three sugar units, these three, and it's going to transfer them up here, right, to a straight chain. And then it's going to pluck off that branch point. And the interesting thing about this particular glucose right there is when it breaks that alpha 1-6 bond, it produces the only true glucose in glycogenolysis, right? So everything else comes off as glucose 1-phosphate except this one glucose comes off as just regular old glucose and you can see the next thing that would have to happen is for this glucose to be phosphorylated, right? So that's not shown in the image but that would have to be the next thing occurring here. And, you know, this is just saying that glycogen phosphorylase starts cutting these off same as normal.

So anyways, let's think big picture for a second. What does high blood glucose lead to? High blood glucose causes insulin to go up, which stimulates glycogen breakdown and I'm sorry, I said that wrong. High blood glucose causes insulin to go up. So glycogen breakdown is lowered from this and glycogen synthesis goes up, right? So insulin causes a reduction in glycogen breakdown and an increase in synthesis. So, oh and also glycolysis. Low blood glucose causes glucagon to go up which leads to glycogen breakdown and reduces glycolysis and glycogen synthesis. It's also going to stimulate gluconeogenesis which is not written here. So I'm just going to kind of add that in—plus gluconeogenesis. Glycogen phosphorylase and glycogen synthase as we already said are phosphorylated and dephosphorylated together. But these processes affect these enzymes in opposite ways, right? So it always leads to the activation of one and deactivation of the other. That way, these two processes are regulated by a very simple mechanism that can control both of them and prevents futile cycles which is always a very important part of metabolic pathways in the cell. Alright, let's flip the page.

Here’s what students ask on this topic:

What is the role of glycogen phosphorylase in glycogen metabolism?

Glycogen phosphorylase is crucial in glycogen metabolism as it mobilizes glycogen by cleaving glucose subunits from the non-reducing ends of glycogen. This enzyme breaks down glycogen into glucose 1-phosphate, which is then converted to glucose 6-phosphate by phosphoglucomutase. Unlike hydrolases that use water to cleave bonds, glycogen phosphorylase uses phosphate, making it a phosphorylase. This process is essential for providing glucose to the body, especially during low blood glucose levels or high energy demands.

How is glycogen phosphorylase regulated?

Glycogen phosphorylase is regulated through phosphorylation. It becomes active when phosphorylated by phosphorylase kinase, which is stimulated by glucagon, epinephrine, and AMP. Conversely, it is deactivated when dephosphorylated. Additionally, high levels of glucose allosterically inhibit glycogen phosphorylase by exposing its phosphate groups, making them easier to remove. This regulation ensures that glycogen breakdown is controlled and prevents futile cycles in metabolism.

What is the difference between glycogen phosphorylase and glycogen synthase in terms of activation?

Glycogen phosphorylase and glycogen synthase have opposite activation mechanisms. Glycogen phosphorylase is activated when phosphorylated, while glycogen synthase is activated when dephosphorylated. This reciprocal regulation ensures that glycogen synthesis and breakdown do not occur simultaneously, preventing futile cycles and ensuring efficient energy storage and mobilization. This mechanism is crucial for maintaining metabolic balance in response to varying blood glucose levels.

What is the function of the debranching enzyme in glycogen metabolism?

The debranching enzyme plays a vital role in glycogen metabolism by transferring three glucose units from a branch to a straight chain and then cleaving the α-1,6 bond at the branch point. This process releases a free glucose molecule, which is the only true glucose produced during glycogenolysis. The remaining glucose units are released as glucose 1-phosphate by glycogen phosphorylase. This action ensures the complete breakdown of glycogen and efficient glucose mobilization.

How do insulin and glucagon affect glycogen metabolism?

Insulin and glucagon have opposite effects on glycogen metabolism. High blood glucose levels increase insulin, which promotes glycogen synthesis and reduces glycogen breakdown. Conversely, low blood glucose levels elevate glucagon, which stimulates glycogen breakdown (glycogenolysis) and inhibits glycogen synthesis. This hormonal regulation ensures that glucose is available when needed and stored when in excess, maintaining blood glucose homeostasis.