Glycogen Metabolism

What is the process of glycogenolysis?

The breakdown of glycogen into glucose-1-phosphate (G1P), which can be converted to glucose-6-phosphate (G6P) for energy metabolism.

Where is glycogen stored in the body?

In cytosolic granules of muscle and liver cells in vertebrates.

Why is G1P important in glycogen metabolism?

It can be converted to G6P, which is used in glycolysis and the citric acid cycle for energy production.

Which enzyme removes glucose residues from glycogen?

Glycogen phosphorylase.

What type of bonds does glycogen phosphorylase act on?

α-1,4 linkages of the glycogen polymer.

What happens when glycogen phosphorylase encounters an α-1,6 branch point?

It stops 4 residues away, and the glycogen-debranching enzyme removes the branch.

What are the two products of glycogen degradation?

Glucose-1-phosphate (G1P) and a free glucose molecule.

What enzyme is central to glycogen synthesis?

Glycogen synthase.

What is the starting point for glycogen synthesis?

Glucose is converted to glucose-6-phosphate (G6P) by hexokinase.

How does glycogen synthase incorporate glucose into glycogen?

By adding glucose to the nonreducing end of a glycogen molecule.

Which hormone promotes glycogen synthesis, and how?

Insulin; it increases glucose transport into cells and activates glycogen synthase.

Which hormone stimulates glycogen breakdown during fasting?

Glucagon.

How does epinephrine affect glycogen metabolism?

It stimulates glycogenolysis for rapid glucose release during the 'fight or flight' response.

How are glycogen phosphorylase (GP) and glycogen synthase (GS) reciprocally regulated?

When one is active, the other is inactive. GP is active when phosphorylated (-P), while GS is active when dephosphorylated (-OH).

What molecule acts as an allosteric regulator for both GP and GS?

Glucose-6-phosphate (G6P): Inhibits GP (active form), Activates GS (inactive form).

What enzyme deficiency causes von Gierke disease?

Glucose-6-phosphatase or glucose-6-phosphate translocase.

What are the hallmark clinical features of von Gierke disease?

Severe fasting hypoglycemia, hepatomegaly, lactic acidosis, growth retardation, and hyperlipidemia.

Why does lactic acidosis occur in von Gierke disease?

The impaired Cori cycle prevents lactate from being converted to glucose, leading to lactate buildup in the blood.

What dietary measures help manage von Gierke disease?

Frequent feeding with uncooked cornstarch to prevent hypoglycemia, and avoiding lactose, fructose, and sucrose.

What enzyme deficiency causes Pompe disease?

Acid α-glucosidase (acid maltase).

Why is Pompe disease classified as a lysosomal storage disorder?

Glycogen accumulates in lysosomes due to a defect in acid α-glucosidase.

What are classic symptoms of infantile Pompe disease?

Macroglossia, hypotonia, cardiomegaly, and muscle weakness.

What therapy has improved outcomes for Pompe disease?

Enzyme replacement therapy for acid α-glucosidase.

What enzyme is deficient in Cori disease?

Debranching enzyme (α-1,6-glucosidase).

How does Cori disease differ from von Gierke disease?

Cori disease has milder hypoglycemia and no lactic acidosis because gluconeogenesis is intact.

What are common treatments for Cori disease?

Cornstarch supplements and a high-protein diet.

What enzyme deficiency causes McArdle disease?

Muscle glycogen phosphorylase (myophosphorylase).

What is the 'second-wind phenomenon' in McArdle disease?

After initial fatigue during exercise, muscles utilize circulating glucose, reducing pain and fatigue.

What dietary strategies benefit patients with McArdle disease?

Pre-exercise glucose loading and consuming complex carbohydrates.

Why must blood glucose levels be tightly regulated?

Glucose is the primary metabolic fuel, especially for the brain, which relies almost entirely on it for energy.

What role does the liver play in maintaining glucose homeostasis?

It regulates dietary fuel distribution, stores glycogen, and supplies glucose to the blood during fasting.