Harper's Biochemistry Chapter 18 - Glycogen Metabolism

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Questions and Answers

What is the role of glycogen in the liver during glucose homeostasis?

To supply free glucose for export into the bloodstream (correct)

To convert glucose to lactate

To provide glucose for glycolysis

To store glucose as glycogen

How is glycogen phosphorylase activated for glycogenolysis?

By dephosphorylation through phosphoprotein phosphatase

By increasing the levels of glycogen synthase

By allosteric regulation via glucose-6-phosphate

By phosphorylation through phosphorylase kinase (correct)

Which hormone directly increases the levels of cyclic AMP in response to glucose demand?

Growth hormone

Epinephrine (correct)

Insulin

Cortisol

What is the effect of phosphorylation on glycogen synthase?

Reduces its activity, inhibiting glycogenesis Signup and view all the answers

What is the genetic condition caused by a lack of lysosomal acid maltase?

Pompe disease (type II glycogen storage disease) Signup and view all the answers

Which enzyme deficiency is associated with von Gierke disease?

Glucose-6-phosphatase Signup and view all the answers

What is a common clinical feature of Pompe disease?

Muscle hypotonia Signup and view all the answers

Which glycogen storage disease is caused by a deficiency in the branching enzyme?

Andersen’s disease Signup and view all the answers

What is a clinical feature of McArdle disease?

Muscle glycogen abnormally high Signup and view all the answers

Which enzyme is deficient in type VII glycogen storage disease?

Muscle phosphorylase Signup and view all the answers

Which condition is characterized by hepatomegaly and mild hypoglycemia, with generally good prognosis?

Hers disease Signup and view all the answers

What complication is associated with Fanconi-Bickel syndrome?

Renal dysfunction Signup and view all the answers

Which enzyme is responsible for the hydrolysis of glycogen to glucose in lysosomes?

Lysosomal α1 → 4 glucosidase Signup and view all the answers

What is the primary role of glucagon during exercise?

Stimulates glycogenolysis in the liver Signup and view all the answers

Which factor contributes to the maintenance of glucose levels during moderate-intensity exercise?

Increased glucagon levels Signup and view all the answers

What characterizes glycogen storage diseases?

Abnormal type or quantity of glycogen deposition Signup and view all the answers

What effect does cAMP-dependent protein kinase have on glycogen metabolism?

Stimulates glycogenolysis by promoting the breakdown of glycogen Signup and view all the answers

What is the effect of insulin on glucose uptake during exercise?

Has no effect on glucose uptake in muscle during exercise Signup and view all the answers

How does hypoglycemia affect a person's ability to function?

It can impair their ability to function Signup and view all the answers

Which of the following substances provides a rapid increase in blood glucose levels?

Glucagon Signup and view all the answers

What causes the rise in glucagon levels during sustained exercise?

Decreased blood glucose levels Signup and view all the answers

What is the main substrate for gluconeogenesis during periods of low glucose availability?

Amino acids Signup and view all the answers

What is the main clinical concern of hypoglycemia in individuals with diabetes?

It prevents the use of glucagon emergency measures Signup and view all the answers

What is the main role of insulin in glycogen metabolism?

It inhibits glycogenolysis and stimulates glycogenesis. Signup and view all the answers

Which enzyme is primarily responsible for breaking down glycogen?

Phosphorylase Signup and view all the answers

What occurs when cAMP concentrations decrease in the context of glycogen metabolism?

Glycogenesis is promoted. Signup and view all the answers

What is a significant consequence of inherited enzyme deficiencies in glycogen metabolism?

Glycogen storage diseases Signup and view all the answers

Which of the following statements is true regarding glycogen storage?

Glycogen is predominantly stored in both the liver and muscle. Signup and view all the answers

What role does glucose-6-phosphatase play in glycogen metabolism?

It is absent in muscle tissue. Signup and view all the answers

How does the activity of phosphodiesterase directly influence glycogen metabolism?

By decreasing cAMP levels. Signup and view all the answers

Which process describes the synthesis of glycogen from glucose?

Glycogenesis Signup and view all the answers

What effect do nutritional measures have on medical crises associated with glycogen storage diseases?

They can prevent many medical crises. Signup and view all the answers

Which of the following correctly describes cAMP's role in glycogen metabolism?

It promotes the simultaneous activation of phosphorylase. Signup and view all the answers

What is the primary reason muscle glycogen is utilized during vigorous exercise?

To serve as a readily available source of glucose-1-phosphate for glycolysis Signup and view all the answers

How does liver glycogen primarily replenish after a meal?

By converting lactate and glucogenic amino acids into glycogen Signup and view all the answers

Which enzyme is crucial for the conversion of glucose-1-phosphate to UDP-glucose in glycogenesis?

UDP-glucose pyrophosphorylase Signup and view all the answers

What hinders muscle glycogen from directly providing free glucose during glycogen breakdown?

Lack of glucose-6-phosphatase in muscle Signup and view all the answers

Which of the following statements is true regarding glycogen storage diseases?

They can result from defects in enzymes involved in glycogen metabolism. Signup and view all the answers

What is the primary function of glycogen in the liver?

To act as a reserve to maintain blood glucose levels Signup and view all the answers

What is the effect of insulin on glycogen synthesis?

It promotes the conversion of glucose into glycogen. Signup and view all the answers

During glycogenolysis, what is the role of glycogen phosphorylase?

To convert glycogen to glucose-1-phosphate Signup and view all the answers

What molecule acts as a precursor for glycogen synthesis during the process of glycogenesis?

UDP-glucose Signup and view all the answers

Which of the following serves a role in the breakdown of muscle glycogen for energy production?

Glucose-6-phosphate Signup and view all the answers

What is the primary benefit of consuming a diet rich in carbohydrates for endurance athletes?

It enhances storage of muscle glycogen over time. Signup and view all the answers

What tissue type contains the highest amount of glycogen in a 70-kg person?

Muscle Signup and view all the answers

How does muscle glycogen play a role in energy during physically exhausting activities?

It is broken down for immediate energy supply. Signup and view all the answers

What is a potential outcome for endurance athletes who do not consume additional calories to match their training regimen?

Depleted glycogen stores. Signup and view all the answers

Which statement correctly describes the process of carbohydrate loading as practiced by some athletes?

It seeks to maximize muscle glycogen prior to events. Signup and view all the answers

Which tissue has the lowest percentage of glycogen storage in a 70-kg person?

Extracellular fluid Signup and view all the answers

What primarily drives the storage of carbohydrates in muscle over days and weeks?

Consistent caloric surplus. Signup and view all the answers

What role does exercise to exhaustion play in the regulation of muscle glycogen stores for endurance athletes?

It triggers a compensatory increase in glycogen consumption. Signup and view all the answers

What is the function of inhibitor-1 in glycogen metabolism?

It inhibits protein phosphatase-1 only after phosphorylation. Signup and view all the answers

Which statement about the effects of insulin on glycogen metabolism is correct?

Insulin increases glucose uptake, leading to increased glucose-6-phosphate levels. Signup and view all the answers

How does cAMP influence the activity of phosphorylase kinase?

It activates phosphorylase kinase through phosphorylation. Signup and view all the answers

What role does glucose-6-phosphate play in insulin signaling related to glycogen metabolism?

It serves as an inhibitor of phosphorylase kinase. Signup and view all the answers

What is a consequence of impaired rapid hepatic glycogen metabolism?

It may cause hypoglycemia if glucose demand exceeds production. Signup and view all the answers

What event occurs in response to the phosphorylation of glycogen phosphorylase?

Increase in its enzymatic activity Signup and view all the answers

Which hormone's action leads to the formation of cyclic AMP?

Epinephrine Signup and view all the answers

What is the primary function of cAMP in glycogen metabolism?

Regulates the activity of glycogen phosphorylase Signup and view all the answers

During exercise, what metabolic change occurs concerning liver glycogen?

Rapid increase in glucose production Signup and view all the answers

How does phosphodiesterase affect cAMP levels during hormonal action?

Decreases cAMP concentration Signup and view all the answers

What distinguishes the role of glycogen phosphorylase in liver versus muscle?

In muscle, it provides glucose-6-phosphate; in liver, it provides free glucose. Signup and view all the answers

What effect does insulin have on phosphodiesterase activity in the liver?

Stimulates phosphodiesterase activity Signup and view all the answers

What immediate effect follows a rapid increase in cAMP levels in response to hormones?

Activation of glycogen phosphorylase Signup and view all the answers

What is the ultimate consequence of a genetic deficiency in lysosomal acid maltase?

Type II glycogen storage disease Signup and view all the answers

Following glycogen breakdown in the liver, what occurs to glucose levels in the plasma?

Glucose levels increase to stabilize blood sugar. Signup and view all the answers

What catalytic activity is peculiar to the debranching enzyme in glycogen metabolism?

Transferring a trisaccharide unit from one branch to another Signup and view all the answers

Which of the following statements is true regarding glucose-6-phosphatase?

It catalyzes the hydrolysis of glucose-6-phosphate to yield glucose Signup and view all the answers

What role does phosphoglucomutase play in glycogen metabolism?

It converts glucose-1-phosphate to glucose-6-phosphate reversibly Signup and view all the answers

During the breakdown of glycogen, which structure remains after sequential removal of glucosyl residues?

Approximately four glucose residues beside a 1 → 6 branch point Signup and view all the answers

Which of the following properties is associated with phosphorylase in glycogenolysis?

It requires a phosphate group for activity Signup and view all the answers

What is the consequence of genetic defects in glucose-6-phosphate transporter?

It leads to hypoglycemia due to impaired glucose release Signup and view all the answers

Which branch of glycogen is a target for the action of glucan transferase in the debranching process?

The 1 → 6 linked branches Signup and view all the answers

What is the function of glucose-6-phosphatase specifically in the liver?

To hydrolyze glucose-6-phosphate, releasing free glucose Signup and view all the answers

What is primarily removed during the action of glycogen phosphorylase?

Glucosyl residues from terminal branches Signup and view all the answers

What forms the catalytic site necessary for the activity of the debranching enzyme in glycogen metabolism?

A single polypeptide chain with dual functions Signup and view all the answers

What role does 5′ AMP play in muscle phosphorylase regulation?

It serves as an allosteric activator for phosphorylase a. Signup and view all the answers

Which statement correctly describes the regulation of glycogen phosphorylase in muscle compared to the liver?

Muscle phosphorylase is inhibited by free glucose while liver is not. Signup and view all the answers

How does the signal for glycogen metabolism differ between muscle and liver during exercise?

Only liver utilizes cAMP in response to low glucose levels. Signup and view all the answers

What is the cascade mechanism that activates phosphorylase kinase?

cAMP leads to the phosphorylation of kinase b to kinase a. Signup and view all the answers

What indicates the need for increased substrate metabolism in muscle cells?

The formation of 5′ AMP from ADP. Signup and view all the answers

What differentiates the allosteric behavior of liver glycogen phosphorylase from muscle phosphorylase?

Liver phosphorylase is not affected by calcium levels. Signup and view all the answers

Which type of enzymes exists for glycogen synthase, and where are they located?

Different isoenzymes exist in brain, muscle, and liver. Signup and view all the answers

What is the effect of ATP and glucose-6-phosphate on phosphorylase a in the liver?

They act as inhibitors to prevent hyperglycemia. Signup and view all the answers

What is the primary role of phosphorylase kinase in glycogen metabolism?

To convert inactive phosphorylase b to active phosphorylase a. Signup and view all the answers

Match the following glycogen storage diseases with their characteristics:

Pompe disease = Deficiency in lysosomal acid maltase Von Gierke disease = Deficiency in glucose-6-phosphatase McArdle disease = Deficiency in muscle phosphorylase Cori disease = Deficiency in debranching enzyme Signup and view all the answers

Match the following terms with their descriptions related to glycogen metabolism:

Glycogenolysis = Breakdown of glycogen to glucose-1-phosphate Glycogenesis = Synthesis of glycogen from glucose-1-phosphate Glucagon = Hormone that increases blood glucose levels Insulin = Hormone that promotes glycogen synthesis Signup and view all the answers

Match the following processes with their roles in glycogen metabolism:

Transamination = Conversion of pyruvate to alanine Gluconeogenesis = Production of glucose from non-carbohydrate sources Glycolysis = Breakdown of glucose for energy Glycogen accretion = Increase of glycogen stores in tissues Signup and view all the answers

Match the following organs with their respective glycogen roles:

Liver = Main reserve for blood glucose regulation Muscle = Immediate source of glucose-1-phosphate for energy Brain = Has minimal glycogen stores compared to liver Kidney = Participates in gluconeogenesis Signup and view all the answers

Match the following elements with their significance in glycogen metabolism:

Cyclic AMP = Second messenger in hormone action Lactate = Precursor for gluconeogenesis in the liver Glucose-6-phosphate = Inhibitor of glycolysis in muscle UDP-glucose = Activated form of glucose for glycogenesis Signup and view all the answers

Match the following terms related to glycogen with their correct descriptions:

Glycogenolysis = Process of breaking down glycogen to glucose Glycogenesis = Synthesis of glycogen from glucose Phosphoglucomutase = Enzyme that converts glucose-6-phosphate to glucose-1-phosphate Branching enzyme = Enzyme involved in creating branch points in glycogen Signup and view all the answers

Match the following enzymes with their functions in glycogen metabolism:

Hexokinase = Phosphorylates glucose to glucose-6-phosphate in muscle Glucokinase = Phosphorylates glucose to glucose-6-phosphate in liver Glycogen synthase = Enzyme responsible for adding glucose units to glycogen Glycogen phosphorylase = Enzyme that catalyzes the removal of glucose from glycogen Signup and view all the answers

Match the following components with their associated storage mechanisms:

Liver glycogen = Supports blood glucose levels Muscle glycogen = Provides energy during exercise Water = Associated with glycogen weight loss during dieting Astrocytes = Non-neuronal cells supporting neurons in glycogen storage Signup and view all the answers

Match the following hormones with their roles in glycogen metabolism:

Insulin = Decreases cAMP levels Glucagon = Increases cAMP levels Epinephrine = Stimulates glycogenolysis during stress Cyclic AMP = Acts as a second messenger to regulate glycogen breakdown Signup and view all the answers

Match the following outcomes with their triggers in glycogen metabolism:

Rapid glycogen synthesis = Occurs after high-carbohydrate meal Muscle glycogen sparing = Maintained by carbohydrate ingestion during exercise Neurologic symptoms = Result from glycogen storage diseases Weight loss = Initial loss from glycogen and associated water Signup and view all the answers

Study Notes

Glycogen: The Major Carbohydrate Reserve

Glycogen is the main carbohydrate storage form in animals, analogous to starch in plants.
It is a branched polymer of α-d-glucose.
Found primarily in the liver and muscle, with smaller amounts in the brain.
Liver glycogen serves as a glucose reserve for extrahepatic tissues, especially during fasting.
Muscle glycogen is the primary source of fuel for muscle contraction.

Synthesis and Breakdown of Glycogen

Glycogen synthesis is called glycogenesis and involves adding glucose units to a growing glycogen chain.
Glycogen breakdown, known as glycogenolysis, releases glucose-1-phosphate from glycogen.
In muscle, glucose-1-phosphate is used directly in glycolysis for ATP production.
Liver, however, can release free glucose into the bloodstream via glucose-6-phosphatase.
Breakdown of glycogen is tightly regulated by hormonal signals, primarily glucagon and insulin.

Hormonal Regulation of Glycogen Metabolism

Glucagon, released during low blood glucose, stimulates glycogenolysis in the liver by activating glycogen phosphorylase.
Insulin, released after a meal, promotes glycogenesis by activating glycogen synthase and inhibiting glycogen phosphorylase.
Cyclic AMP (cAMP) plays a crucial role in integrating the regulation of glycogenolysis and glycogenesis.
cAMP, produced in response to hormones like glucagon and epinephrine, activates protein kinase A, which in turn activates glycogen phosphorylase and inactivates glycogen synthase.

Clinical Aspects of Glycogen Metabolism

Glycogen storage diseases are a group of genetic disorders characterized by the accumulation of abnormal amounts or types of glycogen in tissues.
These disorders are rare and predominantly affect the liver, muscles, heart, and, in some cases, the brain.
The specific clinical features vary depending on the type of enzyme deficiency and the tissues affected.
Early diagnosis and proper management are crucial to prevent complications.

Glycogen Storage Diseases: Key Types

Type 0: Deficient glycogen synthase, resulting in hypoglycemia, hyperketonemia, and early death.
Type Ia (von Gierke disease): Deficiency of glucose-6-phosphatase, leading to accumulation of glycogen in liver and kidneys, hypoglycemia, lactic acidemia, ketosis, and hyperlipemia.
Type II (Pompe disease): Deficiency of lysosomal α1 → 4 and α1 → 6 glucosidase (acid maltase), resulting in glycogen accumulation in lysosomes and muscle weakness.
Type III (Cori/Forbes disease): Deficiency of debranching enzyme, causing accumulation of branched polysaccharide (limit dextrin), fasting hypoglycemia, and hepatomegaly.
Type V (McArdle disease): Deficiency of muscle phosphorylase, leading to poor exercise tolerance and high muscle glycogen levels.
Type VI (Hers disease): Deficiency of liver phosphorylase, resulting in hepatomegaly, glycogen accumulation in the liver, and mild hypoglycemia.
Type VII (Tarui disease): Deficiency of muscle and erythrocyte phosphofructokinase, causing poor exercise tolerance and hemolytic anemia.
Type IX: Deficiency of phosphorylase kinase, affecting liver and muscle, resulting in glycogen accumulation and mild hypoglycemia.
Type X: Deficiency of muscle phosphoglycerate mutase, leading to hepatomegaly and glycogen accumulation in the liver.
Type XI (Fanconi-Bickel): Deficiency of glucose transporter 2, affecting liver and kidneys, causing weak bones, renal dysfunction, and growth retardation.
Type XII: Deficiency of aldolase A, resulting in myopathy, exercise intolerance, and hemolytic anemia.
Type XIII: Deficiency of beta-enolase, causing exercise intolerance and myalgia.
Type XV: Deficiency of glycogenin-1, leading to cardiomegaly.

Carbohydrate Storage

Consuming a diet with ample carbohydrates and calories that meets or exceeds daily expenditure will lead to an increase in muscle glycogen stores over days and weeks.
A 70 kg person can store:
- 90 grams of carbohydrate in liver glycogen
- 245 grams of carbohydrate in muscle glycogen
- 10 grams of glucose in extracellular fluid

Glycogen Metabolism

Glycogen is a branched polymer of glucose that serves as a storage form of carbohydrate in animals.
Liver glycogen is broken down to supply free glucose for the body, while muscle glycogen is used for glycolysis to provide ATP for muscle contraction.
Glycogen is stored as granules in the cytoplasm and is synthesized and broken down through several enzymatic steps.
The first step in glycogen breakdown is catalyzed by glycogen phosphorylase, which releases glucose-1-phosphate from the non-reducing ends of the glycogen molecule.
Glycogen synthase is the enzyme that catalyzes the addition of glucose units to the growing glycogen polymer, using UDP-glucose as the donor.

Regulation of Glycogen Metabolism

Glycogen phosphorylase and glycogen synthase are both regulated by phosphorylation and dephosphorylation, which is controlled by hormonal signals and the energy state of the cell.
The enzymes are also regulated by allosteric mechanisms, which means that their activity is affected by the binding of small molecules.
In liver, glycogen phosphorylase is activated by phosphorylation by phosphorylase kinase, which is itself activated by cAMP.
The increase in cAMP levels is triggered by glucagon, which is secreted in response to low blood glucose levels.
Insulin inhibits the activation of phosphorylase b, and promotes glycogen synthesis by stimulating glucose uptake into the cell.
Muscle glycogen phosphorylase is activated by phosphorylation by phosphorylase kinase, which is in turn activated by calcium ions released during muscle contraction.
Insulin and glucose-6-phosphate also modulate glycogen synthase activity.
The reciprocal regulation of glycogen synthase and phosphorylase ensures that glycogen synthesis and breakdown are coordinated with each other to maintain appropriate blood glucose levels.

Important Considerations

The ability to rapidly fine-tune hepatic glycogen metabolism is critical for maintaining blood glucose levels.
Long-standing diabetes can lead to unawareness of hypoglycemia, potentially posing a serious health risk.