Glycogen Synthesis and Degradation
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- Where is glycogen found?
- In all cell types in tissues that respond to fuel hormones
- What two factors increase glycogen degradation?
- a) low fuel supplies b) response to stress or other metabolic need
- What factor increases glycogen synthesis?
- excess carbohydrates
- In glycogen, what type of linkage do you find in a) branching points⬦ b) linear polymer?
- a) ∂-1,6 linkage… b) ∂-1,4 linkage
- What is the starting point for glycogen synthesis?
- Glycogenin protein acts like a primer (autoglycosylation)
- What happens after glycogenin adds 5-7 glucose molecules to the growing poylmer?
- glycogen synthase starts elongating the polymer
- Where are UDP-glucose molecules added?
- At the reducing end
- What is the value in having glycogen branch?
- Degradation occurs through exoglycosylase, which means it starts at the ends (more branches = more ends = faster degradation)⬦ also more reducing ends = faster synthesis
- Which enzyme makes glucose synthesis possible (export)? And where is it found?
- a)glucose-6-phosphatase (G6Pase), b) only in the liver
- Which organ can dephosphorylate and export glucose?
- Only the liver
- What can organs, other than the liver, do with glucose?
- Use it
- What is the chain of events after low blood sugar occurs?
- decreased glucagon ratio > glycogenolysis > inhibitioin of glycogen synthesis
- What effect does epinephrine have on glycogen?
- epi activates glygenolysis to mobilize stored energy
- Can muscles make glycogen?
- Yes, they have GLUT4, insulin receptors⬦ thus they use glucose for immediate use and to make glycogen
- What is the rate limiting enzyme for glycogen degradation?
- glycogen phosphorylase
- What 3 things stimulate glycogen phosphorylation (glycogen degradation in muscles) during exercise?
- epinephrine, AMP, and calcium release during exercise
- What is the cost, in ATP, for adding another glucose molecule?
- 2 ATP
- What are the 3 reactive steps in adding another glucose molecule to glycogen (including the enzymes?
- glucose enters the cell...a) glucose + ATP -> glucose 6-phosphate (hexokinase or glucokinase) +ADP⬦ b) G6P -> G1P (phosphoglucomutase)⬦ c) G1P -> UDP-glucose (UDP-glucose pyrophosphorylase)
- What impact does the fact that hexokinase has a low Km and glucokinase has a high Km for the liver's role in the body?
- the liver is involved in homeostasis to generate G6P
- While the glycogenin protein can autoglycosylate, what 2 things does it require?
- UDP-glucose and Mg-Mn
- What are the 3 steps in the degradation of glycogen in the liver (and kidneys)?
- a) glycogen + Pi -> glycogen + G1P (no high energy bonds broken here) ⬦ b) G1P -> G6P (phosphoglucomutase)⬦ c) G6P -> Glucose (G6-phosphatase)⬦ leaves the liver (or kidney)
- What are the 3 steps in the degradation of glycogen in muscles?
- a) glycogen + Pi -> glycogen + G1P (no high energy bonds broken here) ⬦ b) G1P -> G6P (phosphoglucomutase)⬦ c) glycolysis
- When glucose is added to a growing glycogen polymer what enzyme catalyzes this reaction and what is lost?
- Glycogen synthase⬦ UDP
- Which enzyme takes a linear segment and moves it?
- Tranferase
- In terms of the linkage, what does the Tranferase do?
- It breaks a ∂-1-4 linkage, moves the strand and reattaches it using a ∂-1,6 linkage, forming a new branch.
- In glycogen degradation, from glycogen(n+1) + Pi --> glycogen (n) + glucose-1-P, are high energy P bonds broken?
- No
- In glycogen degradation, what converts glucose-1-P to G-6-P?
- phosphoglucomutase
- In the liver (or kidney) what is the fate of G6P upon glycogenolysis?
- glycolysis or cellular export
- In glycogen synthesis, which enzyme starts a new branch?
- 4,6-transferase
- In glycogen degradation, which enzyme breaks the 1,4 linkage? And what else is needed to make ~8 G1P?
- glycogen phophorylase⬦ 8 Pi
- In glycogen degradation, what is the role of transferase? What is the remaining 1,6 linked glucose is removed by?
- a) transferase removes about 3-4 residues and place them at the end of another polymer using a 1,4 linkage… b) ∂-1,6 glucosidase
- What is the product of ∂-1,6-glucosidase?
- glucose
- What is the product of transferase?
- G1P
- Which enzyme converts G6P to G1P?
- phosphoglucomutase
- What is special about G1P?
- It is the intermediate point for glycogen synthesis and glycogen degradation
- Which moiety is in the central position in carbohydrate metabolism (glycogen synthesis), and is also involved in the synthesis of proteoglycans, glycoproteins, and a precursor for lactose in mammary tissue?
- UDP-glucose
- What are the regulators of glycogen stores in the liver after exercise or stress? And what effect do they have on the liver?
- (+) blood epi⬦ (+) tissue cAMP⬦ (Ca2+ (+)⬦ b) they ALL cause degradation of glycogen and inhibit synthesis.
- What effect does decreased tissue cAMP have on glycogen stores in the liver?
- tissue degradation down⬦ synthesis up⬦ with increased cAMP the opposite would be true
- What effect do the increase in bloood epi, tissue AMP, Ca2+ calmodulin, and cAMP have on glycogen synthesis, degradation and glycolysis?
- glycolysis and degradation of glycogen are up⬦ synthesis of glycogen are down
- Is glycogen phosphorylase, which mediates glycogen degradation, active or not active when phosphorylated?
- Active
- Is glycogen synthase I, which plays a major role in glycogen synthesis, active or not active when phosphorylated?
- Inactive
- What does the fact that PKA can phosphorylate both glycogen synthase and glycogen phosphorylase imply?
- It has opposite effects on two different pathways
- What is the step between the allosteric activation of PKA and the activation of the a cellular protein, e.g., deactivation of glycogen synthase?
- Active PKA causes the activation (via phosphorylation) of phosphorylation kinase, which activates glycogen phosphorylase, and inactivates glycogen synthase.
- What is the role of the protein phosphatase in regulation of glycogen synthesis/degradation?
- It dephosphorylates glycogen synthase
- What effect do Ca2+ (in response to nerve impulse) and epinephrine have on glycogen synthase/degradation?
- It interacts with calmodulin and phosphorylates phosphorylase kinase and ultimately leads to the phosphorylation and deactivation of glycogen synthase.
- What effect does increased AMP levels (due to muscle) have on glycogen synthase/degradation? What percentage?
- It allosterically activates glycogen phosphorylase and ultimately leads to the phosphorylation and deactivation of glycogen synthase. 80%
- What are the fuel sources for muscle from first to last?
- muscle glycogen > glucose from blood (from liver glycogen) > fatty acid oxidation from muscle TAG > fatty acid from TAG in adipose tissue
- What will a defect in G6-phosphatase (von Gierke's) Type I cause? (in liver) Why? Treatment?
- a) enlarged liver, fasting hypoglycemia, growth failure⬦ b) glucose is not exported and G6P stimulates glycogen synthesis. C) treatment is continuous digestion of carbs
- What will a defect in amylo1,6 glucosidase (debrancher) Type II cause? (in liver)
- Fasting hypoglycemia
- What will a defect in muscle glycogen phosphorylase Type III cause? (in muscle)
- exercise-induced muscle pain, muscle weakness (muscle isozyme is defective)