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79 terms

Glycogenesis and Glycogenolysis

Handout 12
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Glycogenesis
the conversion of glucose to glycogen when the glucose in the blood exceeds the demand
Glycogenolysis
breakdown of glycogen to glucose
What is the preferred energy source for brain and erythrocytes?
Glucose
What is essential in exercising muscles?
Glucose
What is the three primary sources of Glucose
Diet
Gluconeogenesis
Glycogen degradation
What is not the most reliable source to get glucose
Diet (Sporadic)
What is a sustained but slow glucose source?
Gluconeogenesis
What glucose source that is in rapidly mobilizable form?
Glycogen Degradation
Where are the main storage of glycogen?
Muscle and liver
How much glycogen is stored in the muscle
400 g: 1-2% weight of muscle (limited source)
How much glycogen is stored in the Liver
100 g: 6-10% weight of the liver
Which source of glycogen is reserve for muscle contraction?
Muscle
Which source of glycogen is used during early stages of fasting?
Liver
Where in the Liver is glycogen stored?
In the cytoplasmic granules containing most of enzymes required for synthesis and degradation
What is another word for glycogenesis?
Glycogen synthesis
What is another word for glycogenolysis
glycogen breakdown
Does glycogenolysis use the same enzymes as glycogenesis?
No, it uses an independent set of enzymes
What type of bond does glycogen have?
linear α-1,4 and branched α-1,6
How many times does branching occur in glycogen?
every 10-14 glucose unit
What are the primary degration products of glycogenolysis?
Glucose 1-Phosphate and Free glucose
Glucose-1-Phosphate are the result of
Breakage of α-1,4 glycosidic bonds
Free glucose comes from _____.
Released from each α-1,6 linked glucosyl residue
In glycogenolysis, what enzymes is used to cleave α-1,4 glycosidic bonds
Glycogen phosphorylase
Where is the α-1,4 glycosidic bonds cleaved at?
Between glucose residues @ the nonreducing ends
How many enzymes are used in the removal of branches during glycogenolysis?
there are 2:
Glucotransferase and glucosidase
Glucotransferase
Debranching enzyme, transfers the 3 of the 4 remaining glucoses to another branch after the glucose was cleaved
In glycogenolysis: When 3 of the 4 remaining glucose are debranched, what happens to them?
Glucotransferase enzyme is the one that removes them and then it transfers it to the nonreducing end of another chain
Glucosidase
Cleaves off the last glucose on the α-1,6 branch as a free glucose molecule
What happens to the single residue that is broken off from the glycogen?
The single residue is called Glucose 1-Phosphate. The Glu 1-P turns into Glucose 1,6-Phosphate, and then to Glucose 6-Phosphate
Glycogen phosphorylase
breaks down glycogen (n) and Pi into glycogen (n-1) and glucose-1 phosphate - cleaves at the alpha (1-4) bonds. Cannot break alpha (1-6) bonds
What is the pathway to go to Gluc-6-P? Name the enzymes also.
From Glycogen→ (glycogen phosphorylase, glucotransferase, and glucosidase) → Glu-1-P → (Phosphoglucomutase) → Glu-1,6-P → (Phosphoglucomutase)
phosphoglucomutase
An enzyme that transfers a phosphate group on a glucose monomer from the 1' to the 6' position in the forward direction or the 6' to the 1' position in the reverse direction.

To be specific, it facilitates the interconversion of Glucose 1-phosphate and Glucose 6-phosphate.
What enzyme is common in glycogenolysis and glycogenesis?
phosphatase
Glycogen in the liver and muscle.. Explain
Glucose-1-phosphate is converted to G6P - in muscle this enters the glycolytic pathway (first reaction is bypassed - Extra ATP), in the liver glucose 6-phosphatase is used to produce free glucose which can leave the liver and enter the bloodstream
Does the Glu-6-P turns into glucose in the muscle? Explain
No. It stays in the muscle. Gluc-6-P turns straight to energy. Glucose stays in muscles
Does Glu-6-P turns to glucose in the Liver? Explain
Yes. glucose 6-phosphatase is used to produce free glucose which can leave the liver and enter the bloodstream
What kind of reaction is Glycogenesis?
Uphill reaction ( +∆G) requires ATP and UTP
Where does Glycogenesis takes place?
in the cytosol of mitochondria
Where is glycogenesis synthesized from?
molecules of α-D-Glu
What type of energy is used in Glycogenesis?
ATP and UTP
What is α-D-Glu attached to?
UDP (UDP-Glu)
UDP-Glu turns to what?
UDP
What is the source of glycogen synthesis?
UDP-Glu (activated glucose molecule, it is the source of growing glycogen chain)
pyrophosphatase
Removal of 2 Pi from UTP + Glu-1-P and drives the reaction forward
UDP-Glu does what
Adds the glucose residues to growing glycogen chain and transfers glucose to protein primer (base).
Pyrophosphatase is equal to ???
hydrolyze same energy as ATP. Same amount in calories and drives the reaction
Glucose molecules can be added on other existing glycogen molecules.
True
glycogen synthase
Catalyzes the following reaction needed for glycogenesis: primer + UDPG → Primer + 1 glucose + UDP
Essentially adds glucose to the growing glycogen chain

Turned on by insulin and removing phosphate group
Turned off by epinepherine and glucagon and by protein kinase (adding phosphate group)
what enzyme builds bridges in glycogenesis?
branching enzymes
branching enzymes
Fragments from alpha (1,4) glucose chain to C6 of another chain, glycogen synthase - branch elongation (glycogen synthesis)
Where is glucose added to?
nonreducing end (C-4). 4th Carbon always goes for the bonding
What regulates glycogenolysis both covalently and allosterically
glycogen phosphorylase (a and b)
In Glycogenolysis: covalent regulation is stimulated by ____ and ____.
ephinephrine and glucagon
What hormone regulates glycogenolysis in the muscle and liver?
Epinephrine
What hormone regulates glycogenolysis in the liver?
Glucagon
Glycogen phosphorylase is covalently regulated by how?
Addition and removal of a phosphate group
What is a phosphorylated active form in glycogenolysis?
glycogen phosphorylase a
What is a dephosphorylated inactive form in glycogenolysis?
glycogen phosphorylase b
glycogen phosphorylase kinase and glycogen phosphorylase phosphatase
Key enzymes in regulations
What is another secondary messenger other than cAMP?
Ca⁺²
What does glucagon and epinephrine do as regulating hormone for glycogen?
it promotes glycogenolysis:
glucagon → g protein → active adenylyl cyclase → cAMP (+) → activates glycogen phosphorylase kinase b → glycogen phosphorylase kinase a → activates glycogen phosphatase a → glycogen is degraded
What does insulin do as a regulating hormone for glycogen?
It promotes glycogenolysis:
insulin → deactivates glycogen phosphorylase a → glycogen phosphorylase b→ which deactivates glycogen phosphorylase kinase a → glycogen phosphatase kinase b → glycogen
What type of reaction happens when cAMP activates glycogen phosphorylase b to glycogen phosphorylase a?
phosphorylation (adds P)
What is the role of calcium?
it acts as a secondary messenger and causes glycogen degration
Where is calcium released from?
it is released when the muscle contracts and comes from the endoplasmic reticulum.
How does calcium promote glycogenolysis?
Once it is released, it binds to calmodulin subunit of phosphorylase kinase and activates glycogen phosphorylase b without phosphorylation.Then it activates glycogen phosphatase.
howHow is gycogenesis regulated?
1. by the addition and removal of phosphate group in glycogen synthase.
2. insulin and glucagon
How is glycogen synthase covalently modified?
by addition and removal of a phosphate group:
Glycogen synthase a and b:
Dephosphorylated (a) active
Phosphorylated (b) inactive
Glycogen synthase a and b are regulated by
cellular level of cAMP which is regulated by glucagon
glycogen synthesis is upregulated by ___.
Insulin
glycogen synthesis is down regulated by ___.
glucagon
Explain how glucagon down regulates glycogenesis/
Glucagon activates cAMP, activates protein kinase, adds Phosphate to glycogen synthase and it inactivates it to glycogen synthase b (phosphorylated form)
Explain how insulin up regulates glycogenesis
activates glycogen synthase b to glycogen synthase a ( dephosphorylated form)
what down regulates glycogen phosphorylase in the liver?
Glucose-6-P, ATP, and Glucose (means their's a lot of energy in the liver so there's no need to break down glycogen)
What up regulates glycogen phosphorylase in the liver?
Glucose 6-P
What down regulates glycogen phosphorylase in the muscle?
Glucose-6-P and ATP
Why doesn't glucose down regulates glycogen phosphorylase in the muscle?
because it doesn't have to leave the muscle it turns straight to energy
What up regulates glycogen phosphorylase in the muscle
Calcium and AMP (low energy and contraction of muscle)
what up regulates glycogen synthase in the muscle?
glucos 6-P