Glycogenolysis and Storage Diseases

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Questions and Answers

What is the role of insulin in glycogen synthesis?

It inhibits glucagon secretion.

It promotes glycogen breakdown.

It facilitates the addition of glucose to glycogen chains. (correct)

It converts glucose to fatty acids.

What happens to glycogen synthesis after a meal when glucose levels start to fall?

Insulin secretion increases.

Glycogen synthesis continues unaffected.

Glucagon levels remain elevated.

Insulin secretion is reduced, stopping glycogen synthesis. (correct)

Which enzyme is primarily responsible for the breakdown of glycogen?

Amylase.

Glucose-6-phosphatase.

Glycogen synthase.

Glycogen phosphorylase. (correct)

How does muscle cell glycogen differ from liver glycogen?

Muscle cells lack glucose-6-phosphatase, restricting glycogen use to internal needs. Signup and view all the answers

What is the primary hormone that counters the effects of insulin?

Glucagon. Signup and view all the answers

Which disorder is the most common glycogen storage disease?

von Gierke disease. Signup and view all the answers

What is a possible effect of impairments in glycogenolysis?

Liver dysfunction and associated diseases. Signup and view all the answers

What is the role of glucose-6-phosphatase in glycogen metabolism?

It dephosphorylates glucose-6-phosphate for blood glucose regulation. Signup and view all the answers

What is the main role of glycogen phosphorylase in glycogenolysis?

It cleaves the alpha 1-4 glycosidic bonds of glycogen. Signup and view all the answers

How does the glycogen debranching enzyme contribute to glycogenolysis?

It transfers branches to facilitate further degradation. Signup and view all the answers

What is produced when glycogen phosphorylase acts on glycogen?

Glucose-1-phosphate. Signup and view all the answers

What role does phosphoglucomutase play in the metabolism of glucose?

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

In which organs is glucose-6-phosphate typically dephosphorylated to glucose?

Liver, kidney, and intestines. Signup and view all the answers

What is the primary enzyme involved in lysosomal glycogen degradation?

Acid alpha-glucosidase. Signup and view all the answers

What percentage of glycogen degradation in skeletal muscle occurs in lysosomes?

5% Signup and view all the answers

Why is electron microscopy necessary for visualizing glycogen molecules?

Light microscopy cannot resolve the individual glycogen particles. Signup and view all the answers

What phenomenon allows patients to resume exercise after a brief rest in Type VI Glycogen Storage Disease?

Second wind Signup and view all the answers

What is the primary energy source for relief of symptoms before glycogen stores are used during exercise in certain patients?

Sucrose Signup and view all the answers

Which of the following symptoms is NOT associated with Lafora progressive myoclonus epilepsy?

Liver enlargement Signup and view all the answers

What characterizes the structure of glycogen in patients with Lafora bodies?

Longer chains and irregular branch points Signup and view all the answers

What type of acids are uronic acids categorized as?

Sugar acids Signup and view all the answers

What does the uronic acid pathway NOT lead to the formation of?

ATP Signup and view all the answers

Which enzyme converts glucose 6-phosphate to glucose 1-phosphate in the uronic acid pathway?

Phosphoglucomutase Signup and view all the answers

In which cellular location does the uronic acid pathway primarily take place?

Cytoplasm Signup and view all the answers

What is the primary complication associated with untreated von Gierke disease?

Nephropathy and chronic kidney disease Signup and view all the answers

In Pompe disease, what is the underlying cause of glycogen accumulation?

Mutation in lysosomal alpha-glucosidase Signup and view all the answers

Which of the following is a symptom of Cori disease (Glycogen storage disease Type III)?

Hepatomegaly and ketotic hypoglycemia Signup and view all the answers

What is the key distinguishing feature of McArdle disease?

Exercise intolerance and muscle cramping Signup and view all the answers

What treatment approach is primarily recommended for managing von Gierke disease?

Frequent feeds to maintain normal glucose levels Signup and view all the answers

What type of disease is primarily caused by a deficiency of the glycogen debranching enzyme?

Glycogen storage disease Type III Signup and view all the answers

Which of the following is a consequence of glycogen accumulation in Pompe disease?

Muscular hypotonia Signup and view all the answers

Which condition is characterized by the presence of very short outer chains of glycogen?

Cori disease Signup and view all the answers

What is the immediate product formed when glucose 1-phosphate reacts with UTP?

UDP glucose Signup and view all the answers

During the conversion of UDP glucose to UDP glucuronic acid, which molecule is reduced?

NAD+ Signup and view all the answers

Which compound does D-glucuronic acid primarily help to detoxify?

Steroid hormones Signup and view all the answers

What is the result of the oxidation of D-glucuronic acid?

L-gulonate Signup and view all the answers

Which enzyme is responsible for the conversion of 3-keto-L-gulonic acid to L-xylulose?

β-L-gulonate decarboxylase Signup and view all the answers

What is the final step that D-xylulose undergoes before entering glycolysis?

Phosphorylation to D-xylulose 5-phosphate Signup and view all the answers

What effect do drugs like Chlorobutanol and Barbital have on the uronic acid pathway?

They significantly increase the pathway. Signup and view all the answers

Which classification best describes the significance of the uronic pathway?

It is an alternative oxidative pathway for glucose. Signup and view all the answers

Study Notes

Glycogenolysis

Glycogen phosphorylase breaks down glycogen by cleaving terminal glucose residues.
Debranching enzyme removes glucose residues from branches.
Glycogen phosphorylase is regulated allosterically and by phosphorylation.
Glucose-6-phosphate is a key metabolic intermediate used in various pathways (glycolysis, TCA cycle, fatty acid synthesis, Cori cycle, alanine cycle).
Glucose-6-phosphatase converts glucose-6-phosphate to glucose in gluconeogenic organs (liver, kidney, intestines).
Lysosomal degradation of glycogen is mediated by acid alpha-glucosidase (acid maltase).
Muscle cells lack glucose-6-phosphatase and cannot release stored glycogen into the bloodstream.

Glycogen Storage Diseases

Dysfunctions in glycogenolysis lead to glycogen storage diseases (GSD).
GSD can affect various organs (liver, skeletal muscle, brain, kidney).

von Gierke Disease (GSD Type I)

Deficiency in glucose-6-phosphatase.
Leads to severe hypoglycemia, hyperuricemia, lactic acidosis, and increased triglycerides.
Patients exhibit hepatomegaly, doll-like face, delayed motor development, and failure to thrive.
Long-term complications include nephropathy, chronic kidney disease, and renal cancer.
Treatment involves frequent feeding to maintain normal glucose levels.

Pompe Disease (GSD Type II)

Deficiency in lysosomal alpha-glucosidase (acid maltase).
Glycogen accumulates in lysosomes, causing cardiomyopathy and muscular hypotonia.
Glycogen transport to lysosomes is speculated to be through macroautophagy.

Cori Disease (GSD Type III)

Deficiency in glycogen debranching enzyme.
Abnormal glycogen accumulates due to halted glycogenolysis at branching points.
Patients experience ketotic hypoglycemia and hepatomegaly.
Can lead to liver cirrhosis and hepatocellular carcinoma.

McArdle Disease (GSD Type V)

Deficiency in skeletal muscle glycogen phosphorylase.
Liver is spared.
Patients exhibit exercise intolerance, muscle weakness, cramping, and pain.
Elevated creatine kinase levels and myoglobinuria are common.
"Second wind" phenomenon can occur with brief rest during exercise.
Pre-exercise sucrose ingestion can alleviate symptoms.

Type VI Glycogen Storage Disease (Hers Disease)

Deficiency in liver glycogen phosphorylase.
Normal creatine kinase and uric acid levels.
Patients experience growth retardation and liver enlargement.
Hyperlipidemia and ketotic hypoglycemia are common.

Lafora Progressive Myoclonus Epilepsy

Increased phosphorylation of glycogen in various tissues, leading to neuronal toxicity and cell death.
Symptoms include ataxia, seizures, myoclonus, and dementia.
Abnormal phosphorylation of glycogen results in insoluble and degradation-resistant glycogen.
Lafora bodies (conglomerates of inclusion bodies) form.

Uronic Acid Pathway

Alternative pathway for glucose metabolism.
Converts glucose to glucuronic acid, ascorbic acid, and pentoses.
Does not produce ATP.
Main function is to produce D-glucuronic acid for detoxification and mucopolysaccharide synthesis.

Reactions

Glucose-6-phosphate is converted to glucose-1-phosphate.
Glucose-1-phosphate reacts with UTP to form UDP glucose.
UDP glucose is oxidized to UDP glucuronic acid.
UDP glucuronic acid is hydrolyzed to UDP and D-glucuronic acid.

UDP Glucuronate

Source of glucuronate for proteoglycan synthesis.
Involved in conjugation of nonpolar molecules (steroids, drugs, bilirubin) for excretion.

L-Gulonate

Precursor of ascorbate (vitamin C) in animals that synthesize it.
Humans lack L-gulonolactone oxidase and cannot synthesize ascorbic acid.

Regulation

Certain drugs (chlorobutanol, barbital) increase uronic acid pathway activity.
Some drugs enhance ascorbic acid synthesis.

Significance

Alternative oxidative pathway for glucose.
Synthesizes glucuronic acid, pentoses, and vitamin C (except in primates and guinea pigs).
D-glucuronic acid is crucial for detoxification and mucopolysaccharide synthesis.

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Description

This quiz covers glycogenolysis, the biochemical process of breaking down glycogen, and its related storage diseases. Learn about key enzymes like glycogen phosphorylase, the role of glucose-6-phosphate, and the implications of glycogen storage diseases such as von Gierke Disease. Test your knowledge on these metabolic processes and their significance in human health.