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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)?
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)
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)
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