Regulation of Glycogen Metabolism Flashcards
What is energy storage in animals? What about plants?
Animals: glycogen
Plants: starch
Where is glycogen primarily found? How is it stored?
- Liver (10%) and muscle (1-2%)
- Stored in granules
What are the two types of starch granules?
- a-rosettes (contain 20-40 B-particles)
- B-particles (contain glucose with many reducing ends)
Glycogen is depleted after _________ of fasting in the liver, and ______ of strenuous exercise in muscle
12 to 24 hours
1 hour
Is there more glycogen storage or fat storage?
More fat storage
What other tissues store glycogen?
Astrocytes (nervous system), heart, and adipose tissue
What is glycogenesis?
The synthesis of glycogen
Where does glycogenesis take place?
Can take place in any cells that store glycogen, but predominant in liver cells
What is the precursor for glycogenesis?
UDP-Glucose (sugar nucleotide)
What are the two steps to glycogenesis?
1) Formation of UDP-Glucose
2) Formation of the initial short-chains
What does the formation of UDP-Glucose require? Which enzyme catalyzes this step?
- UTP + Glucose
- NDP-Sugar pyrophosphorylase
What does NDP-Sugar pyrophosphorylase do?
- Removes 2 phosphate groups from the nucleotide triphosphate and adds a sugar
- Creates UDP-Glucose
What happens to the pyrophosphate created during the formation of UDP-Glucose?
The pyrophosphate is unstable and is quickly converted to an organic phosphate
What catalyzes the formation of initial short-chains?
Glycogenin (protein)
What does glycogenin contain at the 194th position?
Tyrosine, which has an OH- group
What does the OH- group of glycogenin attack? What does that form?
- OH- group of glycogenin attacks the 1st carbon of UDP-Glucose
- Glucosyltransferase activity adds a glucosyl group in the form of glucose, creating a glycogenin and glucose complex
OH- group of the __ carbon can attack the __ carbon on the next UDP-glucose, which creates a _____ glycosidic bond
4
1
1-4
The chain-extending activity of glycogenin can repeat itself ___ more times, and contain maximum __ carbons
6
8
The elongation of glycogen is catalyzed by what? What is the precursor?
- Glycogen synthase
- UDP-glucose
What does glycogen synthase require?
Requires a short-chain that contains at least 4 glucose molecules
What bond does glycogen synthase create?
- Bond between the 4th carbon of the non-reducing end
of the glycogen chain and the 1st carbon of UDP-Glucose - The 4th carbon of the new glucose now has a non-reducing end
The branching of glycogen is catalyzed by what?
Glycogen-branching enzyme
What does glycogen-branching enzyme do? What does it create?
- Attacks the 4th glycosidic bond and cleaves the long-chain, which reattaches from the 4th glucose
molecule of the new non-reducing end - Creates a 1-6 glycosidic bond
Branching (increases/decreases) water-solubility, and creates _______
increases
new non-reducing ends
Why are non-reducing ends important?
Non-reducing ends are important when glucose is synthesized from the breakdown of glycogen
What are the four steps to glycogenesis and their enzymes?
- Formation of UDP-Glucose (NDP-sugar pyrophosphorylase)
- Initial short-chain synthesis (Glycogenin)
- Elongation (Glycogen Synthase)
- Branching (Glycogen-Branching Enzyme)
What is glycogenlysis? What is the end-product?
- Breakdown of glycogen to yield glucose
- Creates Glucose 1-phosphate as an end-product
What catalyzes glycogenolysis?
Glycogen phosphorylase
Glycogen phosphorylase can only act where?
At the non-reducing end of glycogen
What does glycogen phosphorylase do?
Breaks the 1-4 glycosidic bond and adds a free inorganic
phosphate group
Where does the free inorganic phosphate for glycogen phosphorylase come from?
The free inorganic phosphate comes from a store, and
NOT from ATP; does not require additional energy
What acts as a cofactor for glycogen phosphorylase?
Pyridoxal phosphate
What are the three enzymes of glycogenolysis?
- Glycogen phosphorylase: breaks the 1-4 glycosidic bond
- Glycogen debranching enzyme: breaks the 1-6 glycosidic bond
- Phosphoglucomutase
Glycogenolysis debranching enzyme has two types of activities. What are they?
- Transferase activity
- Glucosidase activity
What is the transferase activity of the debranching enzyme?
Removes the 3 glucose units, and attaches it to the non-reducing end of the longer branch (yellow), leaving one glucose attached with a 1-6 glycosidic bond
What is the glucosidase activity of the debranching enzyme?
- Cleaves the 1-6 glycosidic bond, which removes a glucose
- The long-chain no longer has a branch, and is available for
glycogen phosphorylase to continue
What is the role of phosphoglucomutase?
- Catalyzes the formation of Glucose 6-Phosphate from Glucose 1-Phosphate
- Transfers the phosphate group from carbon 1 to carbon 6
Phosphoglucomutase must be _______ to function
phosphorylated
How does phosphoglucomutase work?
- The phosphorylated serine donates its phosphate groups to the 6th carbon, which now contains two phosphate groups: Glucose 1,6-bisphosphate
- The phosphate group at the 1st carbon is given back to the serine (recycling), leaving behind Glucose 6-Phosphate, which is a metabolite for glycolysis
Where is glucose-6-phosphate dephosphorylated?
In the liver
Glucose 6-phosphate is created in the _______, and is brought to the ___ through the ________ transporter
cytoplasm
ER
G6P transporter (T1)
In the ER, what dephosphorylates G6P? What does that create?
- Glucose-6-phosphatase
- Creates a free glucose and an inorganic phosphate, which can be thrown out of the ER
______ glucose cannot pass through GLUT transporters
phosphorylated
Does muscle contribute to blood glucose concentration? Why?
No since it does not express Glucose 6-phosphatase
Phosphorylase a is the _____ form, which happens when it is ________
active
phosphorylated
Phosphorylase b is the ______ form, which happens when it is _______
inactive
dephosphorylated
What is the role of phosphorylase a?
Cleaves individual glucose molecules from glycogen
What enzyme transforms phosphorylase b to phosphorylase a? What enzyme transforms phosphorylase a to phosphorylase b?
b –> a: phosphorylase b kinase
a –> b: phosphorylase a phosphatase (PP1)
What is phosphorylase b kinase activated by?
- Epinephrine
- Ca2+
- AMP (muscle)
- Glucagon (liver)
What is phosphorylase a phosphatase activated by?
Insulin
Glucagon receptors are present in ______, while epinephrine receptors are present in _______
hepatocytse
myocytes
The activation of glycogen phosphorylase a through GPCR receptors leads to an increase in what?
G1P, and eventually G6P and glucose
Glycogen synthase is active when it is (phosphorylated/dephosphorylated)
dephosphorylated
Phosphorylation of glycogen synthase occurs where?
At 3 serine residues
What activates glycogen synthase?
- Insulin
- G6P
- Glucose
How does insulin activate glycogen synthase?
Inhibits GSK3, which inhibits the phosphorylation of GS
What inactivates glycogen synthase?
- Glucagon
- Epinephrine
Glucagon is only present in _______, while epinephrine is present in ______ and _______
- liver cells
- liver cells
- muscle cells
Glycogenolysis is promoted in which cell type(s)?
Both (liver and muscle cells)
Glycolysis is promoted in which cell type(s)?
- Promoted in muscle cells
- Inhibited in liver cells by PKA
Why is glycolysis promoted in muscle cells, but inhibited in liver cells?
- Muscle cells lack the glucagon receptor
- Muscle cells do NOT produce F26BP, which is involved in the inhibition of glycolysis
Glucogeogenesis is promoted by ______, which can only happen in _____ cells
glucagon
liver
