Glycogenesis and Glycogenolysis

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Handout 12


the conversion of glucose to glycogen when the glucose in the blood exceeds the demand


breakdown of glycogen to glucose

What is the preferred energy source for brain and erythrocytes?


What is essential in exercising muscles?


What is the three primary sources of Glucose

Glycogen degradation

What is not the most reliable source to get glucose

Diet (Sporadic)

What is a sustained but slow glucose source?


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?


Which source of glycogen is used during early stages of fasting?


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


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


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)


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?


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?


What is α-D-Glu attached to?


UDP-Glu turns to what?


What is the source of glycogen synthesis?

UDP-Glu (activated glucose molecule, it is the source of growing glycogen chain)


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.


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?


What hormone regulates glycogenolysis in the liver?


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?


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 ___.


glycogen synthesis is down regulated by ___.


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

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