Formation and Degradation Of Glycogen Flashcards
Which tissues are insulin-sensitive?
Most tissues like adipose and muscles tissue (which use GLUT-4)
Which tissues are insulin-insensitive
Erythrocytes, leukocytes, lens of eye, cornea, liver (GLUT-2), and brain
What does insulin-insensitive mean?
That they don’t need insulin in order to take in glucose
What happens after a meal and blood glucose levels rise and insulin is secreted?
Insulin binds to membrane causing GLUT-4 to go to cell membrane to allow glucose in cell. Insulin-stimulated translocation of GLUT-4 involves the activation of protein kinase B (PKB). Active PKB phosphorylates protiens involved in GLUT-4 translocation.
What happens between meals when the insulin levels decline?
Glucose uptake by muscle is stimulated by the increase in AMP levels and the subsequent activation of AMP-stimulted protein kinase (AMPK). AMPK activation promotes the translocation of GLUT-4 transporters to muscle membrane. AMP is generated in the adenylate kinase reaction
Why is the phosphorylation of glucose important?
It is significant because glucose-6-phosphate cannot pass through the membrane to the extracellular side, since it is not a substrate for the glucose transporters. Thus, glucose-6-phosphate is trapped inside the cell and is committed to further metabolism. It also creates a favorable gradient so glucose continues to enter cell.
Describe basics of hexokinase.
Km = 0.2 mM. Constitutive enzyme. Found in most tissues. Strongly inhibited by the product glucose-6-phosphate.
Describe basics of glucophosphate.
Km = 10 mM. Induced enzyme (insulin is the inducer). In liver and pancreas. Not inhibited by glucose-6-P.
What does the glucokinase regulating protein (GKRP) do?
It binds to glucokinase to inactivate it. It releases glucokinase when glucose levels increase.
Activation of Glycogenolysis by cAMP-directed Pathway:
1. ? 2. This enzyme converts cytoplasmic ATP into cAMP which binds to a cytoplasmic enzyme, protein kinase A (PKA).
- Glucagon binding to the glucagon receptor in the liver activates adenylate cyclase, via G-proteins.
Activation of Glycogenolysis by cAMP-directed Pathway:
1. Glucagon binding to the glucagon receptor in the liver activates adenylate cyclase, via G-proteins. 2. ?
- This enzyme converts cytoplasmic ATP into cAMP which binds to a cytoplasmic enzyme, protein kinase A (PKA).
Activation of Glycogenolysis by cAMP-directed Pathway:
1. Glucagon binding to the glucagon receptor in the liver activates adenylate cyclase, via G-proteins 2. This enzyme converts cytoplasmic ATP into cAMP which binds to a cytoplasmic enzyme, protein kinase A (PKA). 3.?
- cAMP activates PKA by binding to its regulatory subunits and releasing the active catalytic subunits.
Activation of Glycogenolysis by cAMP-directed Pathway:
2. This enzyme converts cytoplasmic ATP into cAMP which binds to a cytoplasmic enzyme, protein kinase A 3. cAMP activates PKA by binding to its regulatory subunits and releasing the active catalytic subunits. 4.?
- PKA activates phosphorylase kinase by phosphorylation, which in turn, phosphorylates glycogen phosphorylase b, thereby converting it to the active phosphorylase a
Activation of Glycogenolysis by cAMP-directed Pathway:
3. cAMP activates PKA by binding to its regulatory subunits and releasing the active catalytic subunits. 4. PKA activates phosphorylase kinase by phosphorylation, which in turn, phosphorylates glycogen phosphorylase b, thereby converting it to the active phosphorylase a. 5. ?
- PKA also phosphorylates glycogen synthase, thereby decreasing its activity. Glycogen synthase has nine serine residues that can be phosphorylated by other kinases.
Activation of Glycogenolysis by cAMP-directed Pathway: 4. PKA activates phosphorylase kinase by phosphorylation, which in turn, phosphorylates glycogen phosphorylase b, thereby converting it to the active phosphorylase a. 5. PKA also phosphorylates glycogen synthase, thereby decreasing its activity. Glycogen synthase has nine serine residues that can be phosphorylated by other kinases. 6.?
6.PKA also phosphorylates inhibitor-1, a protein phosphatase inhibitor protein, thereby making it active. Phosphorylated inhibitor-1 inhibits phosphoprotein phosphatases.
Activation of Glycogenolysis by cAMP-directed Pathway: 5. PKA also phosphorylates glycogen synthase, thereby decreasing its activity. Glycogen synthase has nine serine residues that can be phosphorylated by other kinases. 6.PKA also phosphorylates inhibitor-1, a protein phosphatase inhibitor protein, thereby making it active. Phosphorylated inhibitor-1 inhibits phosphoprotein phosphatases. 7. ?
- As a result of the inhibition of glycogen synthase and the activation of glycogen phosphorylase, glycogen is degraded to glucose-1-P.
Glycogen Storage Diseases: Type I Von Gierke’s Disease: What is the defective enzyme?
Glucose-6-phosphatase
Glycogen Storage Diseases: Type I Von Gierke’s Disease: What are the clinical features?
Massive enlargement of the liver, severe hypoglycemia, ketosis, hyperuricemia, hyperlipemia.
Glycogen Storage Diseases: Type I Von Gierke’s Disease: What are the organs affected?
Liver and kidney
Glycogen Storage Diseases: Type I Von Gierke’s Disease: What happens to glycogen storage?
Increased amount: Normal structure
Glycogen Storage Diseases: Type II Pompe’s Disease: What is the defective enzyme?
alpha-1,4-glucosidase
Glycogen Storage Diseases: Type II Pompe’s Disease: What are the clinical features?
Cardiorespiratory failure, causes death usually before 2
Glycogen Storage Diseases: Type II Pompe’s Disease: What are the organs affected?
Liver, heart, muscle
Glycogen Storage Diseases: Type II Pompe’s Disease: What happens to glycogen storage?
Massive increase, normal structure
Glycogen Storage Diseases: Type III Cori’s disease: What is the defective enzyme?
Amylo-1,6-glucosidase
Glycogen Storage Diseases: Type III Cori’s disease: What are the clinical features?
Similar to 1 but milder
Glycogen Storage Diseases: Type III Cori’s disease: What are the organs affected?
Muscle and liver
Glycogen Storage Diseases: Type III Cori’s disease: What happens to glycogen storage?
Increased amount, short outer branches
Glycogen Storage Diseases: Type IV Anderson’s Disease: What is the defective enzyme?
Branching enzymes (alpha-1,4 – alpha-1,6)
Glycogen Storage Diseases: Type IV Anderson’s Disease: What are the clinical features?
Progressive cirrhosis of the liver
Glycogen Storage Diseases: Type IV Anderson’s Disease: What are the organs affected?
Liver
Glycogen Storage Diseases: Type IV Anderson’s Disease: What happens to glycogen storage?
Normal amount, very long outer branches
Glycogen Storage Diseases: Type V McArdle’s Disease: What is the defective enzyme?
Phosphorylase
Glycogen Storage Diseases: Type V McArdle’s Disease: What are the clinical features?
Limited ability to perform strenuous exercise because of painful muscle cramps
Glycogen Storage Diseases: Type V McArdle’s Disease: What are the organs affected?
Muscle
Glycogen Storage Diseases: Type V McArdle’s Disease: What happens to glycogen storage?
Moderate increase, normal structure
