Liver vs Muscle Glycogen Phosphorylase: Videos & Practice Problems

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

The liver plays a crucial role in maintaining blood glucose levels, particularly during periods of low glucose availability. The enzyme Glycogen Phosphorylase, specifically its active form known as Phosphorylase a, is essential for breaking down glycogen into glucose. This process is vital for supplying glucose to other tissues when blood glucose levels drop. In the liver, Phosphorylase a remains active, continuously providing glucose unless allosterically inhibited by high blood glucose concentrations.

When an individual consumes a glucose-rich meal, such as a cookie, the resulting increase in blood glucose levels triggers a negative feedback mechanism. In this scenario, glucose acts as an allosteric inhibitor of Phosphorylase a, signaling the enzyme to transition from its active R state to the inactive T state. This shift effectively halts the production of glucose from glycogen, as the liver recognizes that sufficient glucose is already available from dietary sources.

The biochemical reaction facilitated by Glycogen Phosphorylase involves the breakdown of glycogen into Glucose 1-Phosphate, which can subsequently be converted into glucose. The presence of high glucose levels in the bloodstream indicates that the liver does not need to release additional glucose, thus conserving energy and resources. This regulation is not solely dependent on allosteric inhibition; it also involves covalent modifications influenced by various hormones, which will be explored in further detail in subsequent lessons.

In summary, the allosteric regulation of liver Glycogen Phosphorylase a is a critical mechanism that ensures glucose homeostasis, allowing the liver to respond appropriately to changes in blood glucose levels. Understanding this regulation sets the stage for comparing it with the allosteric regulation of muscle Glycogen Phosphorylase b, which will be discussed in future lessons.

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.

Answer: (A)

Liver vs Muscle Glycogen Phosphorylase

The allosteric regulation of muscle Glycogen Phosphorylase B plays a crucial role in energy production during muscle contractions. Unlike the liver, which regulates glycogen breakdown for overall glucose supply, muscle tissues utilize glycogen primarily to generate glucose and energy for their own immediate needs during physical activity. In muscle cells, Glycogen Phosphorylase B remains in an inactive state until allosterically activated by specific energy molecules.

During muscle contractions, significant energy fluctuations occur, making muscle glycogen enzymes particularly sensitive to changes in energy status. Key molecules involved in this regulation include glucose 6-phosphate (G6P), adenosine triphosphate (ATP), and adenosine monophosphate (AMP). G6P, an intermediate in glycolysis, can be converted into ATP through cellular respiration. High concentrations of G6P and ATP indicate a high-energy state, which correlates with muscle relaxation. Conversely, elevated AMP levels signal low energy, as they arise from ATP depletion during muscle contractions.

When muscle contractions occur, ATP is converted to AMP, leading to an increase in AMP concentration. This rise in AMP serves as a positive feedback signal that allosterically activates Glycogen Phosphorylase B, shifting it to its active R state. This activation facilitates glycogen breakdown, allowing the muscle to replenish its energy stores. The process can be summarized by the reaction where Glycogen Phosphorylase catalyzes the breakdown of glycogen into glucose 1-phosphate, which can then be converted to G6P and subsequently to ATP.

During intense physical activity, such as weightlifting or running, the muscle's energy demands increase, prompting the conversion of ATP to AMP. This shift not only activates Glycogen Phosphorylase B but also enhances glycogen breakdown to meet energy needs. In contrast, during periods of muscle relaxation, the accumulation of ATP and G6P leads to allosteric inhibition of Glycogen Phosphorylase, reverting it to its inactive state. This dual regulation—positive feedback from low energy indicators like AMP and negative feedback from high energy indicators like ATP and G6P—ensures that muscle glycogen metabolism is finely tuned to the energy requirements of the muscle.

It is important to note that liver Glycogen Phosphorylase does not respond to these energy fluctuations in the same way, as the liver's role is to maintain overall glucose levels rather than respond to immediate energy demands. This distinction highlights the specialized functions of glycogen metabolism in different tissues, ensuring that energy production is efficiently managed according to physiological needs.

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.

Answer: (D)

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.