Glycogen Metabolism Flashcards
Main stores of glycogen?
Which stores larger amount of glycogen?
What does each of these stores use it for?
Muscle and liver
Muscle
Muscle=energy; liver= maintains blood glucose for liver and kidney
All straight chains have what kind of linkages?
1->4 glycosidic linkages
Difference between gluconeogenesis and glycogenesis
Gluconeogenesis= slow to react but reliable Glycogenesis= significant storage with a fast response but only lasts 12-14 hours
Two parts of your body that are dependent on glucose
Brain and RBC
Why can’t muscle glycogen provide blood glucose maintenance?
Due to absence of glucose-6-phosphatase
Where does glycogenesis take place?
What enzymes does glycogenesis require?
Cytosol
Requires glycogen synthase and branching enzyme
What is the rate limiting enzyme for synthesis of glycogen?
Glycogen synthase
What is needed to initiate glycogen synthesis?
Glycogen fragment/glycogenin - has tyrosine attached which auto-glycosylates (meaning it adds glucose molecules)
Give an example of glycosylation
HbA1C
In order to enter glycogenesis, why does glucose need to be activated to UDP glucose?
This activation is necessary so glucose does not enter glycolysis; enters glycogenesis instead (needed for branching enzyme and glycogen synthase to act)
So once you have UDP glucose- glycogen synthase comes and does what?
Elongation- can only act if you have glycogenin or other small chain of glucose. Also, only works on non-reducing ends
- What does it mean to be a nonreducing sugar?
2. Explain which sugars are reducing/nonreducing?
- Anomeric carbon is involved in formation of bond so it cannot oxidize/react (does not have an OH group)
- First sugar is reducing end; all other sugars are nonreducing (remember: nonreducing is important for synthesis of glycogen) Nonreducing ends are the very ends of branches in this case
When does branching enzyme come in?
What does it do?
When glucose chain is long enough
Forms new alpha 1->6 branch and breaks an old alpha 1->4 branch
Importance of what branching enzyme is doing?
Branching enzyme is making multiple branches. Branches are helpful because they are easier to digest and take up a smaller area (liver and muscle are unable to hold long, straight chains)
- Glycogen synthase makes what kind of bonds?
2. Branching enzyme makes what kind of bonds?
- Alpha (1->4) bonds (by further elongation at nonreducing ends)
- Alpha (1->6) bonds (by further branching)
~this eventually makes the branched structure that is glycogen
Glycogenolysis is not reverse of glycogenesis; separate pathway.
- Site?
- What two enzymes does it require?
- Liver and muscle
2. Glycogen phosphorylase and debranching enzyme
Function of glycogen phosphorylase
What is significant about this enzyme
Requres Pi to remove terminal sugars (nonreducing ends) one at a time. Works its way down until it gets to last 3-4 sugars from the branch point. Releases glucose as glucose-1-PO4
It is rate limiting enzyme for glycogen degradation
Function of debranching enzyme?
Once you are down to terminal 3-4 sugars, debranching enzyme removes them to expose branching point
90% of glucose is releases as glucose-1-PO4. What happens to other 10%
Glucose-1-PO4 converts to glucose-6-PO4. This is translocated by translocase into ER lumen where it is converted to free glucose by glucose-6-phosphatase (in liver and kidney).
GLUT2 then transports this free glucose out
Allosteric regulation:
- Glycogen synthesis
- Glycogen degradation
- High levels of energy and substrate
2. Low levels of energy and glucose
Liver: would you make glycogen or degrade it if you have high levels of Glucose-6-phosphate
Make glycogen (check notes app)
Muscle (this part is different than liver): high levels of what two additional things would lead to glycogenolysis
High Ca2+ (which would be during strenuous exercise) and high AMP (because that means low energy)
- Hypoglycemia would initiate what 3 hormones?
- Hyperglycemia would initiate what hormone?
- Stress would initiate what hormones?
- Glucagon, epinephrine and GH
- Insulin
- Cortisol and epinephrine
Insulin does what to key enzyme in glycogenesis?
Glucagon/epinephrine?
Insulin dephosphorylates key enzyme to make it glycogen synthase
Glucagon/epi phosphorylate it to make it glycogen phosphorylase
Breakdown of glycogen is quicker with Ca or with AMP?
Ca
Role of Ca2+ in muscle for glycogen degradation (think cell signaling lecture)
Ca is released from SR during exercise, binds to calmodulin subunit of phosphorylase kinase (activating with w/o phosphorylation) phosphorylase kinase activates glycogen phosphorylase to degrade glycogen
Role of AMP in muscle
Protein kinase A phosphorylates phosphorylase which activates glycogen phosphorylase (has more steps than Ca)
Glycogen storages diseases (GSDs) are mostly autosomal recessive conditions except
Liver phosphorylase kinase deficiency (GSD IX)
Origin and consequences of GSDs
Type 1: Von Gierkes
Liver
G6Pase deficiency (glycogen not broken down normally)
Severe postabsorptive hypoglycemia, lactic acidemia, hyperlipidemia
Round face, hepatomegaly
Origin and consequences of GSDs
Type II: Pompes
Lysosomal alpha glucosidase (Acid maltase) deficiency - accumulation of glycogen vacuoles in cytosol
Affects muscle, liver and heart
Cardiomegaly (floppy baby)
Die before 18 months usually (if doesn’t affect heart its not as severe)
Origin and consequences of GSDs
Type III: Coris
Debranching enzyme deficiency
Very large liver with large stores of glycogen (limit dextrin is type of glycogen deposit in liver and muscle)
Origin and consequences of GSDs
Type IV: Andersons
Branching enzyme deficiency-very severe but very rare
*problem with synthesis, not breakdown
Liver: cirrhosis/heart involvement
Usually die before age 2 (need liver transplant)
Origin and consequences of GSDs
Type V: McArdles
Muscle glycogen phosphorylase deficiency so glycogen in muscle not broken down
Extreme fatigue/muscle damage causing myoglobinuria
Second wind - temporary shift from glycogen to lipids for energy
Origin and consequences of GSDs
Type IV: Hers
Liver
Liver glycogen phosphorylase deficiency
Mild hypoglycemia/hepatomegaly
(Similar to type I but not as severe)
