Glycogen Metabolism and Regulation

The process of controlling glycogen breakdown and synthesis to maintain energy balance in the body.

When two metabolic pathways are controlled so that when one is active, the other is inhibited.

A protein that adds phosphate groups to other proteins, triggering either glycogen breakdown or inhibiting glycogen synthesis, depending on the target protein.

An enzyme that removes phosphate groups from proteins.

The enzyme initially responsible for glycogen breakdown.

The enzyme that synthesizes glycogen from glucose.

The process of restoring muscle glycogen levels after exercise.

Proteins that bind to the catalytic subunit of PP1, affecting its activity and targeting in the cell.

PP1's phosphatase activity isn't always inhibiting glycogen degradation because the activity of protein kinase A keeps it in check, either by releasing its catalytic subunit or by directly inhibiting it.

Epinephrine or glucagon trigger a cAMP cascade to activate protein kinase A, which decreases PP1 effect to stop glycogen synthesis and allow for degradation.

Insulin stimulates glycogen synthesis by increasing glucose entry into the cell and inactivating glycogen synthase kinase (a key enzyme in keeping glycogen synthase inactive).

Insulin binds to its receptor, activating a tyrosine kinase that phosphorylates insulin receptor substrates, triggering pathways that increase glucose transport and inactivate glycogen synthase kinase.

Insulin causes dephosphorylation of glycogen synthase (a), activating it to build glycogen from glucose. This process is counteracted by glycogen synthase kinase.

Phosphorylase enzyme 'a' in the liver senses blood glucose concentration. Glucose binding shifts its form to inactive (T), releasing PP1 for glycogen synthesis.

Active enzyme "b" in the liver doesn't bind phosphatase and activates glycogen synthase, preventing glycogen degradation reactions.

Conversion of phosphorylase 'a' into 'b' occurs before glycogen synthase is activated. This lag prevents concurrent glycogen degradation and synthesis.

Communication between glucose binding site and serine phosphate, proper use of PP1 to regulate both phosphorylase & glycogen synthase, and tight binding of phosphatase to phosphorylase 'a' preventing premature activation of synthase.

Phosphorylase 'b' absence promotes phosphatase release, which activates glycogen synthase and inactivates phosphorylase

Phosphorylase a in the liver acts as a sensor for blood glucose levels, triggering a response to maintain balance.

High blood glucose, led by insulin, triggers glycogen synthesis. This process is stimulated by the increase of glucose uptake into cells.

Inactive form of the enzyme, preventing glycogen synthesis. It is controlled by glycogen synthase kinase.

The enzyme that breaks down glycogen by cleaving glycosidic bonds, releasing glucose 1-phosphate.

The breakdown of a molecule by the addition of orthophosphate.

The product released from glycogen by phosphorylase; can be converted into glucose 6-phosphate for further metabolism.

An enzyme needed to break down the alpha-1,6 bonds at branch points in glycogen.

It produces glucose 1-phosphate, which is already phosphorylated, saving energy compared to hydrolytic cleavage.

It's negatively charged under physiological conditions, and no transporters exist for it.

Phosphorylase can only degrade glycogen to a limited extent due to the alpha-1,6 bonds at branch points, which it cannot break.

Without the debranching enzyme, phosphorylase would only degrade the glycogen molecule to a limited extent, releasing only six glucose molecules per branch.

Different forms of the same enzyme that catalyze the same reaction but have different amino acid sequences and may have different regulatory properties.

An enzyme in the liver that breaks down glycogen, but unlike muscle phosphorylase, it's not regulated by AMP because the liver doesn't have dramatic energy fluctuations like muscle does.

Slow-twitch muscle fibers that rely on cellular respiration for energy, rich in mitochondria and good for endurance activities like long-distance running.

Fast-twitch fibers that rely heavily on glycogen for energy, rich in glycolytic enzymes and poor in mitochondria, best for short bursts of energy like sprinting.

An enzyme that activates phosphorylase b by attaching a phosphate group, controlled by calcium and protein kinase A.

A calcium-binding protein that acts as a sensor in many cellular processes, including activation of phosphorylase kinase.

A series of events where a signal molecule triggers a chain reaction, ultimately leading to a cellular response.

Hormones that trigger the breakdown of glycogen, leading to increased blood glucose levels.

An enzyme that converts glucose 1-phosphate to glucose 6-phosphate, a form suitable for glycolysis.

The process of breaking down glycogen in the liver to release glucose into the bloodstream for use by other tissues.

The process of breaking down glycogen in muscle cells to provide energy for muscle contraction during exercise.

AMP binds to phosphorylase b, stabilizing it in the active conformation, promoting glycogen breakdown in muscle during exercise.

ATP, a high-energy molecule, binds to phosphorylase b and inhibits its activity, slowing down glycogen breakdown.

Glucose binds to phosphorylase a in the liver, shifting it to an inactive state. This prevents unnecessary glycogen breakdown when glucose is already available.

Glucose 6-phosphate inhibits muscle phosphorylase b activity, preventing further glycogen breakdown when sufficient glucose is present for energy production.

The liver both releases glucose into the bloodstream when blood glucose is low and stores glucose as glycogen when blood glucose is high.

Glycogen breakdown is regulated by both allosteric effectors (like AMP and ATP) and phosphorylation/dephosphorylation, ensuring accurate and responsive control.

The T state is the less active form, with a partially blocked active site, while the R state is more active, with an accessible active site.

The glycogen molecule must be remodeled because phosphorylase, the enzyme responsible for glycogen breakdown, can only cleave the α-1,4 glycosidic bonds in the linear portion of the glycogen. Branch points with α-1,6 linkages cannot be cleaved by phosphorylase.

The transferase enzyme shifts a block of three glucose residues from one outer branch of glycogen to another. This process exposes a single glucose residue with an α-1,6 linkage.

α-1,6 glucosidase, also known as the debranching enzyme, hydrolyzes the α-1,6 linkage, releasing a free glucose molecule.

The free glucose molecule is phosphorylated by hexokinase, a glycolytic enzyme, to become glucose 6-phosphate.

Glucose 1-phosphate produced from glycogen breakdown must be converted to glucose 6-phosphate to enter the metabolic mainstream, particularly glycolysis.

Phosphoglucomutase catalyzes the conversion of glucose 1-phosphate to glucose 6-phosphate by transferring a phosphoryl group. It involves a phosphorylated serine residue in the active site, which acts as an intermediate.

Glucose 6-phosphatase is a hydrolytic enzyme found in the liver. It removes the phosphate group from glucose 6-phosphate, releasing free glucose into the bloodstream.

Most tissues retain glucose 6-phosphate for ATP production. In contrast, glucose is not a major fuel for the liver, which primarily releases glucose for other tissues.

Glycogen phosphorylase is the primary target of regulation in glycogen breakdown. It is controlled by both allosteric effectors and reversible phosphorylation.

Phosphorylase a is the usually active, phosphorylated form, while phosphorylase b is the usually inactive, unphosphorylated form. Phosphorylase a favors the active relaxed state, while phosphorylase b favors the inactive tense state.

The liver's role is to maintain blood glucose levels. Therefore, the default state of liver phosphorylase is the active a form to release glucose unless signaled otherwise.

Binding of glucose to the active site of liver phosphorylase a shifts it from the active R state to the less active T state. This is a feedback mechanism to prevent unnecessary glycogen breakdown when glucose is already available.

Muscle requires glucose primarily during contraction. Therefore, the default state of muscle phosphorylase is the inactive b form, which is activated by AMP, signaling low energy.

AMP binds to a nucleotide-binding site on muscle phosphorylase b, stabilizing it in the active R state. This activates glycogen breakdown for energy production.

ATP, a high-energy molecule, acts as a negative allosteric effector by competing with AMP. This slows down glycogen breakdown when the muscle has enough energy.