Flashcards in Metabolism Review Slides: Glycogen and Glycogen Metabolism Deck (25):
Describe the statement "hepatic and muscle glycogen serve different roles"
Hepatic glycogen is broken down back into glucose in times of fasting in order to maintain normal blood glucose levels.
Muscle glycogen is NOT used to increase blood glycogen in times of hypoglycemia. Muscle glycogen is mobilized during exercise for extra energy.
Why is glucose able to leave the cell from the liver and increase blood glucose concentrations, but not from skeletal muscle?
Glycogen is broken down into glucose-1-phosphate and then glucose-6-phosphate.
In the liver: glucose-6-phosphatase removes the phosphate and allows glucose to exit the cell.
In other tissue: there is no glucose-6-phosphatase, and therefore glucose-6-phosphate is stuck in the cell (like the first step of glycolysis). Mobilized glycogen can only be used as a source of energy (ATP production)
Where is more glycogen stored, the muscles or the liver?
The muscles store 400g of glycogen, while the liver can only store 100g of glycogen.
What is the fate of glucose in the liver during times of high blood glucose levels.
Following a meal, glucose and insulin levels are high. Glucose enters hepatic tissue via GLU2 (low affinity) and is stored as GLYCOGEN and FATTY ACIDS and is used to generated ATP through GLYCOLYSIS.
All of these processes are stimulated by insulin.
What is the fate of glycogen in the liver during times of fasting/starvation?
During times of fasting/starvation, glycogen in the liver is broken down and converted back to glucose to maintain normal blood glucose levels.
This processes is stimulated by glucagon (only glucagon receptors in the liver)
What happens to glucose in skeletal muscle after a meal?
After a meal, insulin and glucose levels are high. Insulin stimulates the insulin-dependent uptake of glucose into the skeletal muscle through GLUT4 (high affinity) facilitated diffusion glucose transporters. Some glucose is stored as GLYCOGEN, and the rest is metabolized through glycolysis to produce ATP
What is the fate of skeletal muscle glycogen during exercise?
During exercise, epinephrine and muscle contraction stimulate the breakdown of glycogen in skeletal muscle. Glycogen undergoes glycolysis in order to generate ATP.
What two enzymes are required for the synthesis of glycogen from UDP-glucose?
Glycogen synthase: adds glucosyl units in an alpha-1,4 linkage
Branching enzyme: starts new branches of the glycogen at the specific angles (an alpha-1,6 linkage)
Compare the osmolality of glucose vs. glycogen
Glucose is osmotically active, whereas glycogen is not
What two enzymes are required for the breakdown of glycogen back into glucose 1-P ?
Glycogen phosphorylase: removes glycogen units from the long strands (breaks alpha-1,4 linkages)
Debranching enzyme: removes the alpha-1,6 linkages that start new branches, along with transferase activity
Glycogen phosphorylase, the enzyme responsible for breaking the alpha-1,4 linkages in the breakdown of glycogen back to glucose 1-P, is regulated by multiple second messenger pathways. What are they?
cAMP (through PKA)
PI (through DAG and PI3)
All three second messenger systems activate glycogen phosphorylase through activation of phosphorylase kinase. This stimulates glycogen breakdown.
How does phosphorylation affect the activity of glycogen phosphorylase?
Phosphorylation of glycogen phosphorylase converts it to its active form (phosphorylation activates glycogen degradation)
Dephosphorylation deactivates glycogen phosphorylase.
How does insulin inhibit glycogen phosphorylase?
Insulin inhibits glycogen phosphorylase by promoting dephosphorylation of the enzyme, which inactivates it. This aids in the promotion of glycogen synthesis during times of high glucose.
Insulin promotes glycogen storage.
What are the two forms of glycogen phosphorylase?
Phosphorylase a: phosphorylated and active
Phosphorylase b: dephosphorylated and inactive
How do allosteric regulators of glycogen phosphorylase affect its activity?
Under times of high AMP (exercise), AMP binds directly to the b-form, activating it, and promoting glycogen degradation
Similiarly, when Glucose and ATP are high (high energy state), they may bind directly to glycogen phosphorylase A and inhibit it. This promotes glycogen storage during times of high energy
How is glycogen synthase activity affected by phosphorylation?
Glycogen synthase is activated by DEPHOSPHORYLATION
How does insulin affect glycogen synthase?
Insulin promotes the dephosphorylation and therefore activation of glycogen synthase
How does glucagon affect glycogen synthase?
Glucagon promotes the phosphorylation and consequent inhibition of glycogen synthase
How is glycogen synthase allosterically regulated?
Under certain pathologic conditions, when glucose-6-phosphate is high, it binds to glycogen synthase b form and allosterically activates it
(high glucose-6-phosphate --> allosteric activation of glycogen synthase b)
Can both glycogen synthase and glycogen phosphorylase be allosterically inhibited AND stimulated?
No- only phosphorylase can be both inhibited and stimulated allosterically
Glycogen synthase is only stimulated allosterically by high concentrations of glucose-6-phosphate
Briefly describe the overall theory of glycogen phosphorylase and synthase allosteric vs covalent modification regulation
Covalent modifications: phosphorylation activates synthase and dephosphorylation activates phosphorylase, changing them from their "b" forms to their "a" forms.
Allosteric regulation: binding of allosteric regulators to the "b" forms activates both synthase and phosphorylase. Binding of allosteric regulators to phosphorylase "a" inhibits its activity
What reaction is catalyzed by glucose 6-phosphate dehydrogenase?
Glucose 6-phosphate --> 6-phospho gluconate
This enzyme is a part of the pentose phosphate pathway, important for the generation of NADPH.
What clinical manifestation is genetic deficiency of glucose 6-phosphate dehydrogenase associated with?
When G6PD is not working, the pentose phosphate pathway is inhibited. This leads to a decrease in available NADPH.
NADPH is necessary for the reduction of glutathione. Reduced glutathione is required for protection against ROS. This is especially important in RBCs, where there is no other pathway to generate NADPH (because there is no mitochondria to generate NADPH)
What is the protective role of NADPH in red blood cells?
NADPH maintains glutathione in a reduced state that helps protect red blood cells against oxidative damage.
When NADPH is low in RBCs, levels of ROS rise, causing damage to the cells.