Liver vs Muscle Glycogen Phosphorylase - Online Tutor, Practice Problems & Exam Prep

The liver Glycogen Phosphorylase a is primarily responsible for breaking down glycogen to release glucose for other tissues, remaining active unless high blood glucose levels signal it to switch to the inactive form via allosteric inhibition. In contrast, muscle Glycogen Phosphorylase b activates during muscle contractions when energy is low, responding to AMP through positive feedback, while ATP and glucose 6-phosphate inhibit it during relaxation. This regulation highlights the distinct roles of glycogen breakdown in liver and muscle tissues, emphasizing the importance of allosteric interactions in metabolic processes.

Liver vs Muscle Glycogen Phosphorylase

So now that we're somewhat familiar with the Glycogen Phosphorylase enzyme, in this video we're going to continue to distinguish between the liver and muscle Glycogen Phosphorylase. And so we're going to specifically focus on allosteric regulation of liver Glycogen Phosphorylase a. And then later in another video, we'll talk about allosteric regulation of muscle glycogen phosphorylase. It turns out that we can better understand allosteric regulation of liver glycogen phosphorylase a if we understand the role of glycogen breakdown in the liver, which is to form glucose for export to other tissues when blood glucose is low. The liver is very unselfish, and its glycogen breakdown is to form glucose for other tissues. Therefore, in the liver, the default Glycogen Phosphorylase form is going to be Phosphorylase a, which is the active form. In the liver, phosphorylase stays active and keeps providing glucose to other tissues unless it's allosterically signaled to stop making glucose for other tissues. If the blood glucose concentrations are already really high, such as after eating a glucose-rich meal like a cookie, then in that instance, glucose is going to act as an allosteric inhibitor to phosphorylase a via negative feedback, and we'll be able to talk more about this negative feedback down below in our image.

Liver Glycogen Phosphorylase a is going to remain in its active form and keep providing glucose to other tissues, and it's really only going to revert back to its inactive t state when it already detects sufficiently high glucose concentration in the blood. If we take a look down below at our image, notice we're showing you what happens in the liver after a glucose-rich meal, such as eating a cookie. At the top is the same reaction that we have seen before in our previous lesson videos where we have a glycogen molecule being broken down, shortening the chain and releasing a single glucose molecule as a Glucose 1P Phosphate. Glycogen Phosphorylase, specifically liver Glycogen Phosphorylase in the liver, catalyzes this. This glucose 1P phosphate that's released can be converted into many different forms, and one of those forms is just a glucose molecule. If we eat a cookie, at that point, that's going to be considered a glucose-rich meal and our blood is going to contain a very high concentration of glucose. If we're already obtaining lots of glucose, there's no need for the liver phosphorylase to continue to provide glucose if we're obtaining it through our diet like this. When glucose concentration is high enough via negative feedback, it can actually act as an allosteric inhibitor to the Phosphorylase a form. In the liver, it's normally going to be in the Phosphorylase a r state. However, when we eat a high glucose meal, there is negative feedback, and that can transition the enzyme from the Phosphorylase a r state to the Phosphorylase b t state. There's allosteric inhibition by glucose and also notice there has to be a form of covalent modification to go from the Phosphorylase a form to the Phosphorylase b form. This covalent modification is complex and includes multiple types of hormones, and we'll talk more about this covalent modification later in our course in a different video. For now, what we can see is allosteric regulation by glucose acting as an allosteric inhibitor and switching it from the on form to the off form down here. This concludes the allosteric regulation of liver Glycogen Phosphorylase a and we'll be able to compare this to allosteric regulation of muscle Glycogen Phosphorylase b in our next lesson video. So, I'll see you guys in our next video.

A patient comes into your clinic suffering from anorexia nervosa. Her mother brought her in concerned as the patient has not eaten in over 3 days. She has the classic presentation including low body weight, decreased muscle mass, decreased glycogen, and decreased fat stores, and she is anemic (low red blood cell count). What would be the expected phosphorylation state and activity of the patient's liver glycogen phosphorylase?

• A. Phosphorylated & active.
• B. Dephosphorylated & active.
• C. Phosphorylated & inactive.
• D. Dephosphorylated & inactive.

Liver vs Muscle Glycogen Phosphorylase

So now that we've covered allosteric regulation of liver Glycogen Phosphorylase A, in this video, we're going to talk about allosteric regulation of muscle Glycogen Phosphorylase b. And we can better understand this by understanding the role of glycogen breakdown in our muscle tissues. The role of glycogen breakdown in our muscle tissues, unlike the role in our liver tissues, is to form glucose and energy for itself only during a muscle contraction. Therefore, in our muscle tissues, the default Glycogen Phosphorylase is going to be Glycogen Phosphorylase B and that's because glycogen phosphorylase b is going to stay in the inactive state unless it's allosterically signaled to create energy for a muscle contraction.

Now, in our muscle cells during a muscle contraction, there's going to be drastic energy changes. For that reason, our muscle glycogen enzymes are going to be sensitive to regulation by energy molecules such as glucose 6-phosphate (G6P), ATP, and AMP. G6P is just an abbreviation for glucose 6-phosphate, an intermediate molecule of glycolysis that can be converted into ATP via cellular respiration. High concentrations of G6P and ATP indicate high energy within the cell, which is associated with muscle relaxation since when the muscle is relaxed, there's a buildup of these high-energy molecules.

On the other hand, high AMP concentrations indicate low energy within the cell because it's associated with muscle contractions; muscle contractions deplete ATP and form AMP. During contractions, there's this depletion of energy within the cell. The depleted ATP results in more AMP, and the resulting AMP is going to allosterically activate phosphorylase B via positive feedback. The muscle glycogen phosphorylase b is going to stay inactive and only revert to its active R state when it detects low energy due to muscle contractions depleting the energy within the cell.

Let's take a look down below at our image to clear some of this up. What I want you guys to notice is that we're specifically focusing on during intense muscle contraction, such as if you're pumping weights in the gym or if you're in the middle of a marathon. At the top here, what we have is the same exact reaction that we saw in our previous lesson videos where glycogen phosphorylase is responsible for breaking down the glycogen, shortening the glycogen chain while releasing glucose as glucose 1-phosphate. Subsequent reactions can convert the glucose 1-phosphate into glucose 6-phosphate (G6P), which, as an intermediate in glycolysis, can be converted into ATP. ATP and G6P are high-energy indicators and indicate, when they build up, muscle relaxation. Here, during intense muscle contractions, the energy built up, the ATP can be used in a muscle contraction. The ATP will be converted into the low-energy molecule AMP. AMP is going to allosterically activate the phosphorylase B and help shift it to the phosphorylase A R state. This is going to occur via positive feedback. The muscle contraction which generates AMP allows AMP to allosterically activate the phosphorylated B T state, shifting it from the phosphorylase B T state to the phosphorylase A R state and allowing for more glycogen breakdown and replacement of the energy that was being depleted.

Normally, in our muscle tissues, the phosphorylase is going to be in the B form, in phosphorylase b form in the T state. It's only during a muscle contraction where it will shift into the Phosphorylase A R state. During relaxation, there's an energy buildup in the cell, and the resulting G6P and ATP are capable of allosterically inhibiting phosphorylase A so that it can essentially convert back into the form that it's normally in during muscle relaxation. G6P and ATP here are capable of allosteric inhibition of phosphorylase B via negative feedback. Muscle Glycogen Phosphorylase experiences both positive feedback from the low energy molecules and negative feedback from the high energy molecules.

You may wonder why liver phosphorylase is insensitive to regulation by these molecules; it has to do with the fact that the liver does not undergo drastic energy changes like our muscles do, making them insensitive to regulation by these energy molecules. This concludes our lesson on Allosteric Regulation of Muscle Glycogen Phosphorylase B, and we'll be able to get some practice utilizing these concepts in our next video. So, I'll see you guys there.

Muscle glycogen phosphorylase displays multiple modes of allosteric regulation. Which of the following is true?

• A. AMP promotes conversion of R to T state.
• B. ATP favors the conversion of the T to R state.
• C. G6P promotes conversion of the T to R state.
• D. If ATP is needed, phosphorylation converts the enzyme from the phosphorylase b to the phosphorylase a form.
• E. Phosphorylation is mediated by phosphoprotein phosphatase 1.

Here’s what students ask on this topic:

What is the primary function of liver Glycogen Phosphorylase a?

The primary function of liver Glycogen Phosphorylase a is to break down glycogen to release glucose for other tissues. This enzyme remains active unless high blood glucose levels signal it to switch to the inactive form via allosteric inhibition. The liver is unselfish in its role, providing glucose to maintain blood sugar levels for other tissues, especially during fasting or between meals. This regulation ensures that other tissues have a steady supply of glucose, highlighting the liver's critical role in maintaining overall metabolic homeostasis.

How does allosteric regulation of muscle Glycogen Phosphorylase b differ from liver Glycogen Phosphorylase a?

Muscle Glycogen Phosphorylase b is regulated primarily by the energy needs of the muscle. It activates during muscle contractions when energy is low, responding to AMP through positive feedback. In contrast, ATP and glucose 6-phosphate inhibit it during muscle relaxation. On the other hand, liver Glycogen Phosphorylase a remains active to provide glucose to other tissues and is inhibited by high blood glucose levels via allosteric inhibition. This difference highlights the distinct roles of glycogen breakdown in liver and muscle tissues, with muscle glycogen serving immediate energy needs and liver glycogen maintaining blood glucose levels.

What role does AMP play in the regulation of muscle Glycogen Phosphorylase b?

AMP plays a crucial role in the regulation of muscle Glycogen Phosphorylase b by acting as an allosteric activator. During intense muscle contractions, ATP is depleted, leading to an increase in AMP levels. This high concentration of AMP signals low energy within the muscle cell and activates Glycogen Phosphorylase b via positive feedback. The activation of this enzyme facilitates the breakdown of glycogen into glucose 1-phosphate, which can then be converted into glucose 6-phosphate and subsequently ATP, replenishing the energy supply needed for continued muscle contraction.

Why is liver Glycogen Phosphorylase a insensitive to regulation by energy molecules like ATP and AMP?

Liver Glycogen Phosphorylase a is insensitive to regulation by energy molecules like ATP and AMP because the liver does not undergo drastic energy changes like muscle tissues do. The primary role of liver glycogen breakdown is to maintain blood glucose levels for other tissues, rather than responding to the liver's own energy needs. Therefore, its regulation is more closely tied to blood glucose levels, with high glucose acting as an allosteric inhibitor. This ensures that the liver can continuously provide glucose to other tissues, regardless of its own energy status.

How does glucose act as an allosteric inhibitor for liver Glycogen Phosphorylase a?

Glucose acts as an allosteric inhibitor for liver Glycogen Phosphorylase a by binding to the enzyme and signaling that blood glucose levels are sufficiently high. This binding induces a conformational change in the enzyme, switching it from its active form (Phosphorylase a) to its inactive form (Phosphorylase b). This negative feedback mechanism ensures that the liver stops breaking down glycogen to release glucose when there is already an adequate supply of glucose in the blood, preventing unnecessary glucose production and maintaining metabolic balance.