U01.01.116 Glycogen

Understanding glycogen metabolism is essential for the USMLE Step 1. This includes the processes of glycogen synthesis, degradation, and the various enzymes involved. Below is a detailed breakdown to help you prepare for the exam.

Key Concepts in Glycogen Metabolism

Glycogen Structure

Branching: Glycogen contains α-(1,6) bonds at branch points.
Linkages: The main chain of glycogen is held together by α-(1,4) glycosidic bonds.

Glycogenolysis

Skeletal Muscle Glycogen: During exercise, glycogen in skeletal muscle undergoes glycogenolysis to form glucose-1-phosphate, which is further converted to glucose-6-phosphate for energy production.
Hepatic Glycogen: In hepatocytes, glycogen is stored and degraded to maintain blood glucose levels.

Glycogen Degradation Mechanism

Glycogen Phosphorylase: Breaks down glycogen by cleaving α-(1,4) bonds, releasing glucose-1-phosphate.
Debranching Enzyme:
1. 4-α-D-glucanotransferase: Moves three glucose units from the branch to the main chain.
2. α-1,6-glucosidase: Cleaves the last glucose unit, releasing free glucose.

Limit Dextrin

Limit Dextrin: The remaining fragment of glycogen after glycogen phosphorylase has shortened the chain. It consists of 2–4 glucose units at the branch point.

Key Enzymes Involved in Glycogen Metabolism

Enzyme	Function	Disease Association
Glycogen Synthase	Catalyzes glycogen synthesis	Von Gierke disease
Branching Enzyme	Forms α-(1,6) bonds at branch points	–
Debranching Enzyme (4-α-D-glucanotransferase)	Moves glucose from branch to main chain	Cori disease
Debranching Enzyme (α-1,6-glucosidase)	Cleaves the last glucose unit from the branch	–
Glycogen Phosphorylase	Cleaves α-(1,4) bonds, releasing glucose-1-phosphate	McArdle disease

Common Glycogen Storage Diseases

McArdle Disease: A deficiency of glycogen phosphorylase in muscles, leading to muscle weakness and cramps during exercise.
Cori Disease: A deficiency in the debranching enzyme, resulting in the accumulation of limit dextrin.
Pompe Disease: A deficiency in α-1,4-glucosidase (acid maltase) in lysosomes, leading to glycogen accumulation in lysosomes.
Von Gierke Disease: A deficiency of glucose-6-phosphatase, leading to impaired gluconeogenesis and fasting hypoglycemia.

Additional Enzyme Details

UDP-glucose Pyrophosphorylase: Plays a role in the synthesis of UDP-glucose, a precursor for glycogen synthesis.
α-1,4-Glucosidase (Acid Maltase): Involved in the degradation of glycogen in lysosomes.

Points to Remember

Glycogen degradation in muscle releases glucose-1-phosphate, which enters glycolysis.
In liver cells, glycogen degradation maintains blood glucose during fasting or between meals.
Glycogen phosphorylase and debranching enzymes are crucial for breaking down glycogen.
Glycogen storage diseases (e.g., McArdle, Cori, Pompe, Von Gierke) result from deficiencies in enzymes involved in glycogen metabolism.
Limit dextrin refers to the partial degradation product left after glycogen phosphorylase has acted.

Glycogen Metabolism Summary

Step	Process	Enzyme Involved	Disease
1	Glycogen degradation	Glycogen phosphorylase	McArdle disease
2	Branch removal	4-α-D-glucanotransferase	Cori disease
3	Cleaving the last glucose unit	α-1,6-glucosidase	–
4	Glucose release	–	Pompe disease (lysosomal degradation)

Conclusion

Mastering the enzymes and their roles in glycogen metabolism, along with associated diseases, will be vital for success on the USMLE Step 1 exam.

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