Glycogen Metabolism: Synthesis and Breakdown — MCQs
Which glycogen storage disease does not affect muscles?
Most important carbohydrate store for maintaining blood glucose homeostasis -
An 8-month-old infant is brought in with poor feeding, lethargy, hypotonia, and hepatomegaly. Labs reveal hypoglycemia and metabolic acidosis. Which condition is most likely?
Which is branching enzyme?
Glycogen storage disorders are primarily classified under which type of disorders?
Which of the following is active in dephosphorylated state?
Low insulin to glucagon ratio leads to increase in the activity of
Which glycogen storage disease also presents as a lysosomal storage disease?
When the insulin:glucagon ratio is decreased, which enzyme is active?
Glucose can be synthesized from all except
Glycogen Metabolism: Synthesis and Breakdown Indian Medical PG Practice Questions and MCQs
Question 1: Which glycogen storage disease does not affect muscles?
- A. Type 4 (Andersen disease)
- B. Type 2 (Pompe disease)
- C. Type 1 (Von Gierke disease) (Correct Answer)
- D. Type 3 (Cori disease)
Explanation: ***Type 1 (Von Gierke disease)*** - This is caused by a deficiency in **glucose-6-phosphatase**, an enzyme found primarily in the **liver** and **kidneys** but **NOT in muscle tissue**. - Since muscles do not express glucose-6-phosphatase and rely on glycogen phosphorylase for energy mobilization, this disease **does not affect muscle function**. - Clinical features include severe **hypoglycemia**, **lactic acidosis**, **hepatomegaly**, and **growth retardation**, but patients have **normal muscle strength and function**. *Type 2 (Pompe disease)* - Also known as **acid maltase deficiency**, this disease severely affects **all muscle types** including cardiac, skeletal, and smooth muscles. - It is a **lysosomal storage disease** causing progressive **muscle weakness**, **cardiomyopathy**, and **respiratory failure**. - This is the most significant muscle-affecting GSD. *Type 3 (Cori disease)* - Caused by **debranching enzyme (amylo-1,6-glucosidase) deficiency**, affecting both **liver and muscles**. - Patients develop **hepatomegaly**, **hypoglycemia**, and progressive **myopathy** with muscle weakness. - Muscle involvement is common and clinically significant. *Type 4 (Andersen disease)* - Due to **branching enzyme deficiency**, primarily causing **liver cirrhosis** and **hepatosplenomegaly**. - While mainly hepatic, this disease **can involve muscles** causing hypotonia and muscle weakness in some patients. - The abnormal, unbranched glycogen ("amylopectin-like") accumulates in multiple tissues including muscle.
Question 2: Most important carbohydrate store for maintaining blood glucose homeostasis -
- A. Blood glucose
- B. Glycogen in adipose tissue
- C. Hepatic glycogen (Correct Answer)
- D. None of the options
Explanation: ***Hepatic glycogen*** - The liver contains **100-120g of glycogen**, which is the most crucial carbohydrate store for **maintaining blood glucose homeostasis**. - **Hepatic glycogen** can be mobilized and released as glucose into the bloodstream to supply all body tissues, especially during fasting. - Although muscle glycogen is quantitatively larger (~400-500g), it cannot contribute to blood glucose as muscle lacks glucose-6-phosphatase. - The liver's unique ability to release free glucose makes hepatic glycogen the **most metabolically important** carbohydrate store. *Blood glucose* - **Blood glucose** (~5g total in circulation) represents carbohydrates available for immediate energy, not a storage form. - This is far too small to be considered a major carbohydrate reserve. *Glycogen in adipose tissue* - **Adipose tissue** primarily stores **fat (triglycerides)**, with negligible glycogen content. - Adipose tissue plays virtually no role in carbohydrate storage. *None of the options* - This is incorrect because **hepatic glycogen** is indeed the most important carbohydrate store for glucose homeostasis.
Question 3: An 8-month-old infant is brought in with poor feeding, lethargy, hypotonia, and hepatomegaly. Labs reveal hypoglycemia and metabolic acidosis. Which condition is most likely?
- A. Hereditary fructose intolerance
- B. Galactosemia
- C. Pompe disease
- D. Von Gierke disease (Correct Answer)
- E. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
Explanation: ***Von Gierke disease*** - **Type I glycogen storage disease** (GSD I) typically presents in infancy with **hypoglycemia** (due to impaired glucose release from glycogen), **hepatomegaly** (due to glycogen accumulation), and **lactic acidosis**. - Other common findings include **hyperlipidemia** and **hyperuricemia**, while **hypotonia** and **poor feeding** are generalized symptoms stemming from metabolic derangements. *Hereditary fructose intolerance* - This condition presents when **fructose** is introduced into the diet, typically after 4-6 months of age, with symptoms like **nausea, vomiting, abdominal pain**, and **hepatomegaly**. - While it can cause **hypoglycemia** and **metabolic acidosis**, the profound **hypotonia** and general metabolic collapse described in an 8-month-old on a typical diet makes GSD I more likely initially. *Galactosemia* - Symptoms usually appear within days or weeks of birth upon the initiation of **milk feeding**, including **vomiting, lethargy, poor feeding, jaundice, hepatomegaly**, and **cataracts**. - While it causes **hypoglycemia** and can lead to acidosis and hypotonia, the age of presentation and lack of specific mention of jaundice or cataracts makes it a less precise fit. *Pompe disease* - Also known as **glycogen storage disease type II**, it is characterized by the accumulation of glycogen in **lysosomes**, primarily affecting muscles. - The infantile form presents with severe **cardiomyopathy**, **muscle weakness**, and **hypotonia**, but **hypoglycemia** and **hepatomegaly** are not its primary or most prominent features. *Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency* - A **fatty acid oxidation disorder** that presents with episodic **hypoglycemia** (particularly during fasting or illness), **lethargy**, and **hepatomegaly**. - Key distinguishing features include **hypoketotic hypoglycemia** and elevated **dicarboxylic acids** on urine organic acids, but the **lactic acidosis** and overall metabolic profile are more consistent with GSD I.
Question 4: Which is branching enzyme?
- A. Glycogen synthase
- B. Amylo-1, 4-1, 6-transglycolase (Correct Answer)
- C. Glycogen Phosphorylase
- D. Glucose-6 phosphatase
Explanation: ***Amylo-1, 4-1, 6-transglycolase*** - This enzyme is also known as **glycogen branching enzyme**. - It catalyzes the formation of **α-1,6-glycosidic bonds** by transferring a segment of four to six glucosyl residues from the non-reducing end of a growing glycogen chain to another chain. *Glycogen synthase* - This enzyme is responsible for the **elongation of glycogen chains** by forming **α-1,4-glycosidic bonds**. - It adds glucose units to the non-reducing end of a pre-existing glycogen primer. *Glycogen Phosphorylase* - This enzyme is involved in **glycogen degradation**. - It catalyzes the **phosphorolytic cleavage** of α-1,4-glycosidic bonds, releasing glucose-1-phosphate. *Glucose-6 phosphatase* - This enzyme is primarily found in the **liver** and kidneys and is crucial for **gluconeogenesis** and **glycogenolysis**. - It dephosphorylates glucose-6-phosphate to **free glucose**, allowing its release into the bloodstream.
Question 5: Glycogen storage disorders are primarily classified under which type of disorders?
- A. Endocrine disorders
- B. Metabolic disorders (Correct Answer)
- C. Genetic disorders
- D. Lysosomal storage disorders
Explanation: ***Metabolic disorders*** - Glycogen storage disorders involve defects in the enzymes responsible for **glycogen synthesis** or degradation. - These enzymatic defects lead to abnormal accumulation or breakdown of **glycogen**, thus affecting cellular metabolism. *Genetic disorders* - While glycogen storage disorders are **inherited** and thus genetic, their primary classification focuses on the **metabolic pathways** affected. - This category is too broad and refers to the origin, not the specific functional impairment. *Lysosomal storage disorders* - These disorders involve defective lysosomal enzymes leading to the accumulation of various **substrates within lysosomes**. - Glycogen storage disorders primarily involve enzymes in the **cytoplasm** (or sometimes lysosomes for Pompe disease, but the general classification is metabolic). *Endocrine disorders* - Endocrine disorders involve dysfunction of **hormone production** or regulation. - Glycogen storage diseases are disorders of **carbohydrate metabolism** and do not directly involve hormonal imbalance as their primary pathology.
Question 6: Which of the following is active in dephosphorylated state?
- A. PEPCK
- B. Pyruvate Carboxylase
- C. Glycogen Synthase (Correct Answer)
- D. Glycogen Phosphorylase
Explanation: ***Glycogen Synthase*** - **Glycogen synthase** is primarily active in its **dephosphorylated state**, which is promoted by insulin and signals glycogen synthesis. - Dephosphorylation relieves the inhibitory effect of phosphorylation, allowing the enzyme to efficiently add glucose units to a **growing glycogen chain**. *PEPCK* - **Phosphoenolpyruvate carboxykinase (PEPCK)** activity is primarily regulated at the transcriptional level, not typically by phosphorylation state for activation. - Its expression is induced by **glucagon** and **cortisol** during gluconeogenesis. *Pyruvate Carboxylase* - **Pyruvate carboxylase** is allosterically activated by **acetyl-CoA** and its activity is not directly regulated by phosphorylation/dephosphorylation in the same manner as glycogen synthase. - This enzyme plays a key role in **gluconeogenesis** by converting pyruvate to oxaloacetate. *Glycogen Phosphorylase* - **Glycogen phosphorylase** is active in its **phosphorylated state**, particularly the 'a' form, which is promoted by glucagon and adrenaline for glycogen breakdown. - Phosphorylation activates the enzyme, leading to the **breakdown of glycogen** into glucose-1-phosphate.
Question 7: Low insulin to glucagon ratio leads to increase in the activity of
- A. Hexokinase
- B. Glucokinase
- C. Glucose-6-phosphatase (Correct Answer)
- D. Pyruvate kinase
Explanation: ***Glucose-6-phosphatase*** - A low **insulin to glucagon ratio** signals a state of **low blood glucose**, leading to increased **glucagon** secretion. - Glucagon activates **gluconeogenesis** and **glycogenolysis** in the liver, and **glucose-6-phosphatase** is a key enzyme in the final step of both pathways, releasing free glucose into the bloodstream. *Hexokinase* - This enzyme is responsible for the **phosphorylation of glucose in most tissues** to trap it within the cell for glycolysis. - Its activity is generally high during periods of **high glucose and insulin levels** to promote glucose utilization. *Glucokinase* - This is an isoform of hexokinase found in the **liver and pancreatic beta cells**, with a higher Km for glucose, meaning it is active primarily at **high glucose concentrations**. - Its activity is increased by **insulin**, promoting glucose uptake and utilization in times of plenty. *Pyruvate kinase* - This enzyme catalyzes the final step of **glycolysis**, converting phosphoenolpyruvate to pyruvate. - Its activity is stimulated by **insulin** and inhibited by **glucagon**, reflecting its role in glucose breakdown, not production.
Question 8: Which glycogen storage disease also presents as a lysosomal storage disease?
- A. Von Gierke's disease
- B. McArdle's disease
- C. Andersen's disease
- D. Pompe's disease (Correct Answer)
Explanation: ***Pompe's disease*** - Also known as **glycogen storage disease type II**, it is caused by a deficiency of **acid alpha-glucosidase (GAA)**, a *lysosomal enzyme*. - This deficiency leads to the accumulation of **glycogen in lysosomes**, particularly affecting muscle tissue, thereby earning its classification as both a glycogen storage disease and a lysosomal storage disease. *Von Gierke's disease* - This is **glycogen storage disease type I** and is due to a deficiency in **glucose-6-phosphatase**. - It primarily affects the **liver and kidneys**, causing severe **hypoglycemia** and **lactic acidosis**, but it is not classified as a lysosomal storage disease. *McArdle's disease* - This is **glycogen storage disease type V**, caused by a deficiency in **muscle glycogen phosphorylase (myophosphorylase)**. - It manifests as **exercise intolerance** and muscle pain, but it does not involve lysosomal enzyme defects or glycogen accumulation in lysosomes. *Andersen's disease* - This is **glycogen storage disease type IV**, caused by a deficiency in the **glycogen branching enzyme**. - It leads to the formation of **abnormal glycogen structures**, primarily affecting the liver and causing early liver failure, but it is not a lysosomal storage disorder.
Question 9: When the insulin:glucagon ratio is decreased, which enzyme is active?
- A. Glucokinase
- B. Phosphofructokinase
- C. Hexokinase
- D. Glucose-6-phosphatase (Correct Answer)
Explanation: ***Glucose-6-phosphatase*** - A decreased insulin:glucagon ratio indicates a **fasting state** or **catabolic state**, promoting glucose production and release rather than storage. - **Glucose-6-phosphatase** is the key enzyme that enables glucose release from the liver by removing the phosphate group from glucose-6-phosphate, producing free glucose that can exit hepatocytes. - This enzyme is active during both **gluconeogenesis** and **glycogenolysis** and is only present in liver, kidney, and intestinal cells. *Glucokinase* - **Glucokinase** is active in the **fed state** when insulin levels are high and the insulin:glucagon ratio is increased. - It phosphorylates glucose to trap it in hepatocytes for glycogen synthesis and metabolism, which is the opposite of what occurs during fasting. *Phosphofructokinase* - **Phosphofructokinase (PFK-1)** is the rate-limiting enzyme of **glycolysis**, active when glucose needs to be broken down for energy. - It is stimulated by high insulin:glucagon ratios and inhibited during fasting when gluconeogenesis (the reverse pathway) is active. *Hexokinase* - **Hexokinase** phosphorylates glucose in peripheral tissues for intracellular utilization. - During a low insulin:glucagon ratio, the priority is glucose **release** from the liver, not glucose **uptake** and phosphorylation in tissues.
Question 10: Glucose can be synthesized from all except
- A. Acetoacetate (Correct Answer)
- B. Amino acids
- C. Lactic acid
- D. Glycerol
Explanation: ***Acetoacetate*** - **Acetoacetate** is a **ketone body** and is metabolized to **acetyl-CoA**. - **Acetyl-CoA** cannot be converted to pyruvate or oxaloacetate and thus cannot be used for **gluconeogenesis**. *Amino acids* - Many **amino acids** are **glucogenic**, meaning they can be converted into **glucose**. - They enter the gluconeogenic pathway at various points, such as **pyruvate** or **oxaloacetate**. *Lactic acid* - **Lactic acid** is converted to **pyruvate** by **lactate dehydrogenase** as part of the **Cori cycle**. - **Pyruvate** is a direct precursor for **glucose synthesis** via **gluconeogenesis**. *Glycerol* - **Glycerol**, derived from triglyceride breakdown, can be converted to **dihydroxyacetone phosphate** (DHAP). - **DHAP** is an intermediate in gluconeogenesis, allowing for **glucose production**.
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