Glycogen Metabolism 1: Videos & Practice Problems

Glycogen, a branched storage molecule of glucose, features alpha 1,4 glycosidic linkages in its straight chains and alpha 1,6 bonds at branch points. Synthesized by glycogen synthase using UDP glucose, its activity is regulated by insulin, which inhibits GSK3 (glycogen synthase kinase 3) and activates protein phosphatase 1. This process is crucial for glucose storage, especially when glucose 6-phosphate levels rise. Branching enzyme facilitates the formation of branches by transferring sugar subunits, enhancing glycogen's compact structure for efficient energy storage.

Glycogen Metabolism 1

Let's continue our story of metabolism with Glycogen, the storage molecule that contains glucose. Now, glycogen is a highly branched structure, and the reason for this is actually because it saves a lot of space in the cell to have all this branching. The straight chains of glycogen are made with alpha-1,4 glycosidic linkages between the glucose units, whereas the branch points on the molecule have alpha-1,6 glycosidic bonds. The sugar chains tend to be about 12 to 14 subunits long. So looking at this figure here, imagine that each one of these little chains is about 12 to 14 units long. The core of glycogen is actually a protein, and it's a protein called glycogenin. And you can see it right here in the center of our glycogen. The first sugars of glycogen are actually hooked onto tyrosine residues in glycogenin. Glycogen is made by glycogen synthase, and this is a synthase meaning it doesn't use nucleotide triphosphates like ATP. Instead, it uses something called UDP-glucose. So that's, uracil diphosphate glucose. And, the UDP is actually released from the reaction. It elongates the strands of sugars at the non-reducing end. And as we already said, it usually forms chains about 12 to 14 subunits long.

GSK3 normally phosphorylates and inactivates glycogen synthase. You might remember this from biosignaling. Insulin, the indicator of high blood sugar, inhibits GSK3, and that's how glycogen synthase is activated. So, insulin inhibits the thing that inhibits glycogen synthase and then glycogen synthase can take that sugar out of the blood and store it as glycogen. Protein phosphatase 1 dephosphorylates glycogen synthase. So, it's going to activate it. GSK3 is the thing that inactivates glycogen synthase, but protein phosphatase 1 has to actually activate glycogen synthase. Protein phosphatase 1 is stimulated by insulin. So, let's think about this for a second. Insulin turns off the thing that shuts down glycogen synthase and turns on the thing that turns on glycogen synthase. Pretty cool, right? This speaks to what we were talking about previously with biosignaling and how one signaling molecule can lead to the activation of so many different things. Protein phosphatase 1 is also stimulated by glucose-6-phosphate. As soon as glucose enters the cell, it's going to become glucose-6-phosphate. If there's a buildup of glucose-6-phosphate, it's going to stimulate protein phosphatase 1 to turn on glycogen synthase to start storing some of that glucose. It is also stimulated by glucose and it's inhibited by glucagon and epinephrine. Glucagon and epinephrine are both molecules that cause blood sugar to go up. They are released in response to low blood sugar to try to raise the blood sugar. Clearly, you don't want glycogen synthase running if you want your blood sugar higher. You want to be mobilizing the sugar, not storing it. You can see a little diagram of how glycogen synthase fits into our model of glycolysis. Here we have hexokinase and then to convert the glucose into glycogen, it has to go through a few steps. You don't need to worry about the specific mechanism. Just know that glycogen synthase uses UDP-glucose, leaves UDP behind, and it adds a glucose subunit onto the sugar chain.

We've been talking this whole time about how to make straight chain sugars. But as we said in the beginning, glycogen is branched. So how does glycogen make those branches? Simply with branching enzyme which basically takes 6 to 10 subunits of sugar from the chain formed by glycogen synthase, and it transfers those subunits onto the 6th position of a glucose. Here in black, we have our straight chain, and here is that portion that was transferred. Of course, here we're only showing 3, but as we said, it transfers about 6 to 10 subunits. And it attaches them at that 6th position, so you form an alpha-1,6 bond. Branching enzyme just transfers; it doesn't actually build the polymer like synthase does.

Alright. Let's turn the page.

Here’s what students ask on this topic:

What are the structural differences between the straight chains and branch points in glycogen?

Glycogen is a highly branched storage molecule of glucose. The straight chains in glycogen are formed by alpha-1,4 glycosidic linkages between glucose units. In contrast, the branch points are created by alpha-1,6 glycosidic bonds. These branches occur approximately every 12 to 14 glucose units, making glycogen a compact and efficient storage form of glucose. The branching is facilitated by a branching enzyme that transfers 6 to 10 glucose subunits from a straight chain to the 6th position of another glucose unit, forming the alpha-1,6 bond.

How does insulin regulate glycogen synthase activity?

Insulin regulates glycogen synthase activity by inhibiting glycogen synthase kinase 3 (GSK3) and activating protein phosphatase 1 (PP1). GSK3 normally phosphorylates and inactivates glycogen synthase. When insulin is present, it inhibits GSK3, preventing the inactivation of glycogen synthase. Additionally, insulin stimulates PP1, which dephosphorylates and activates glycogen synthase. This dual action ensures that glycogen synthase is active, allowing glucose to be stored as glycogen when blood sugar levels are high.

What role does UDP-glucose play in glycogen synthesis?

UDP-glucose (uridine diphosphate glucose) is a key substrate in glycogen synthesis. Glycogen synthase uses UDP-glucose to elongate the glycogen chain. During this process, the glucose unit from UDP-glucose is added to the non-reducing end of the glycogen chain, and UDP is released. This reaction does not require ATP, making it an efficient way to store glucose. The enzyme glycogen synthase continues to add glucose units, forming chains that are typically 12 to 14 subunits long.

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

The branching enzyme plays a crucial role in glycogen metabolism by creating the branched structure of glycogen. It transfers a segment of 6 to 10 glucose subunits from a straight chain to the 6th position of another glucose unit, forming an alpha-1,6 glycosidic bond. This branching increases the solubility and compactness of glycogen, allowing for more efficient storage and rapid mobilization of glucose when needed. The branched structure also provides multiple sites for enzymatic action during glycogen breakdown.

How do glucagon and epinephrine affect glycogen synthase activity?

Glucagon and epinephrine inhibit glycogen synthase activity. These hormones are released in response to low blood sugar levels and aim to increase blood glucose. They activate signaling pathways that lead to the phosphorylation and inactivation of glycogen synthase. By inhibiting glycogen synthase, glucagon and epinephrine prevent the storage of glucose as glycogen, ensuring that glucose remains available in the bloodstream for immediate energy needs.