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1) Describe the role of glycogenolysis in the regulation of blood glucose levels. 2) Define reciprocal regulation of metabolic pathways. 3) Describe the reactions catalyzed by glycogen phosphorylase & by the debranching enzyme. 4) Describe the reactions following the formation of glucose-1-phosphate. 5) List the products of glycogen degradation. 6) Describe how glycogen phosphorylase is regulated in liver & in muscle and list the signals that stimulate or inhibit glycogenolysis in the mu…

How does Glycogenolysis aid in regulation of blood glucose levels?

Glycogenolysis is the degradation of glycogen stores. This occurs in the Liver in the Fasting State, and releases glucose into the circulation (for RBC - only source of energy, and the brain - Gluc is primary source of energy)

How is Glycogenolysis used in skeletal muscle?

Glycogenolysis occurs in skeletal muscle during exercise (can only be used by muscle)
Produces Glucose from Glycogen, which is then oxidized through Glycolysis

How does reciprocal regulation affect Glycogenolysis during Fasting State?

Glycogenolysis is stimulated, and Glycogenesis is inhibited (Avoiding Futile Cycling)
*the opposite occurs during the Fed State

Once the body goes into fasting state, how long until the Liver's Glycogen stores are depleted (and Gluconeogenesis is the only source of Glucose)?

24 hours

In Glycogenolysis glucose residues are removed form what end of the glycogen molecule?

The non-reducing ends

What enzyme is responsible for breaking the alpha(1,4) bonds between glucose chain residues? What is used in the process? What co-factor is required? What is the product?

Glycogen Phosphorylase (uses Pi)
Co-factor: Pyridoxal Phosphate (PLP)
Product: Glucose-1-Phosphate (92% of glucose in glycogen molecule)

Branch Removal take place after the non-reducing end of the glycogen molecule is how many residues away from the branch point?

4 Glucose Residues away from the branch point

What enzyme is responsible for the removal and degradation of alpha(1,6) bonds at branch points? What is produced?

Debranching Enzyme degrades the alpha(1,6) bonds
Product: Glucose (8% of glucose in glycogen molecule)

What 2 reactions convert Glucose-1-Phosphate to Glucose in the Liver?

1) Phosphoglucomutase (reversible reaction, converts G1P to G6P)
2) Glucose-6-Phosphatase (only in the Liver, converts G6P to Glucose)

Describe the hormonal stimulation of Glycogen Phosphorylase

Glucagon: Activates Protein Kinase A = phosphoryllates Phosphorylase Kinase = Phosphorylase Kinase ON = phosphorylates Glycogen Phosphorylase = Glycogen Phosphorylase ON = Glycogenolysis ON

Describe the hormonal inhibition of Glycogen Phosphorylase

Insulin: Activates Protein Phosphatase 1* = dephosphorylates Phosphorylase = Glycogen Phosphorylase OFF = Glycogenolysis OFF

*Protein Phosphatase also dephosphorylates Phosphorylase Kinase = Phosphorylase Kinase OFF = Glycogen Phosphorylase OFF = Glycogenolysis OFF

Describe the allosteric effectors of Glycogen Phosphorylase

ATP, Glucose-6P & Glucose = Glycogen Phosphorylase OFF (fee-back inhibition)

Review Glucagon cascade

Review Insulin cascade

What serves as the exercise signal for Glycogenolysis in Muscle? (3 possible signals)

1) Neurotransmitter Signaling (Epinephrine [adrenaline] activates Protein Kinase A (Phosphorylase Kinase ON = Glycogen Phosphorylase ON)

2) Muscle contraction (Ca2+ release = Phosphorylase Kinase ON = Glycogen Phosphorylase ON)

3) Exercise (AMP buildup = Glycogen Phosphorylase ON)

What enzyme is missing in Type 1: Von Gierke's Disease?

Glucose-6-phosphatase (only in liver, causing Hypoglycemia & Hematomegaly)

What enzyme is missing in Type 2: Pompe's Disease?

alpha-1,4-Glucosidase (lysosomal, very sever clinical features)

What enzyme is missing in Type 3: Cori/Forbes Disease?

Debranching Enzyme (mild hypoglycemia & hepatomegaly)

What enzyme is missing in Type 4: Andersen's Disease?

Branching Enzyme (Hepatomegaly, Cirrhosis, Liver failure, death by 2 years)

What enzyme is missing in Type 5: McArdle's Disease?

Glycogen Phosphorylase (Fatigability, muscle cramps, muscle has increased glycogen)

What enzyme is missing in Type 6: Her's Disease?

Glycogen Phosphorylase

What enzyme is missing in Type 7: Tarui's Disease?


What enzyme is missing in Type 8 Glycogen Storage Disease?

Phosphorylase Kinase

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