Ch 15 - Glycogen metabolism Flashcards by Saskia Steltman

Which protein is involved in the synthesis of a glycogen granule?
a. Glycogen synthase
b. Glycogen phosphorylase
c. Glycogenin
d. Glycogen synthase kinase 3 (GKS3)

Glycogenin

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Which of the following is/are true for the enzyme Glycogen phosphorylase?
a. generation of glucose1P
b. generation of glucose6P
c. generation of UDP glucose
d. hydrolysis breaking of the α1-4 glycosidic bond
e. removal of the α1-6 branches

a: generation of glucose1P
d: hydrolysis of breaking the α1-4 glycocidic bond

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Glycogen synthesis can occur in the _ .
a. muscle.
b. liver.
c. muscle and liver.
d. saliva.
e. brain cells.

muscle and liver

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What are the two activities of the debranching enzyme?
a. transferase and glycosylase
b. phosphorylase and transferase
c. Phosphoglucomutase and phosphorylase
d. UDP-sugar-pyrophosphorylase and pyrophosphatase

phosphorylase and transferase

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What is the metabolic intermediate produced by the glycosylase activity of the debranching enzyme?

Glucose 1-phosphate

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The bond that is broken by the debranching enzyme is a(n)
a. α1-4 glycosidic bond
b. α1-6 glycosidic bond
c. β1-4 glycosidic bond
d. β1-6 glycosidic bond

α1-6 glycosidic bond

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Glycogen phosphorylase activity is regulated extensively. Among the regulatory mechanisms are (mark all that apply)
a. Sequestration
b. Hormonal control
c. Allosteric modification
d. Covalent modification
e. Activation by proteolysis

a. Sequestration
b. Hormonal control
c. Allosteric modification
d. Covalent modification

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The Glucose 1-phosphate formed from glycogen breakdown in skeletal muscle will , for muscle contraction, but will in the liver.
a. enter gluconeogenesis, be released into the bloodstream

b. enter glycolysis, enter gluconeogenesis.

c. enter glycolysis, be released as lactate into the blood.

d. enter glycolysis, be released as glucose into the blood.

e. enters gluconeogenesis; be released as lactate into the blood

enter glycolysis
enter gluconeogenesis

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Under which circumstances would glycogenesis (glycogen synthesis) be possible at somewhat elevated rates? Choose all that may apply.

a. When eating a high carbohydrate meal after 24 hours of fasting

b. When blood sugar levels are high

c. When proteins are used as carbon source

d. When blood sugar levels are low

e. After the secretion of insulin

a. When eating high carb meal after 24h fasting

b. when blod sugar levels are high

e. After secretion of insulin

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What is the product of the glycosylase activity of the debranching enzyme?
a. Glucose
b. Glucose1P
c. Glucose 6P
d. UDP-Glucose

Glucose 1P

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Predict under which circumstances the enzyme glucose-6-phosphatase is active in the muscle.
a. During starvation to provide glucose to the brain

b. When glucose is plentiful after a meal

c. Glucose-6-phosphatase is never active in the muscle

d. When the liver needs glucose for gluconeogenesis

c. Glucose-6-phosphatase is never active in the muscle

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Glycogen synthesis is driven by
a. the hydrolyzation of P~P into 2 Pi
b. the attachment of UDP to glucose1P
c. ATP hydrolysis
d. The generation of α1-4 glycosidic bonds

d. The generation of α1-4 glycosidic bonds

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Glycogen synthesis requires the input of
a. ATP
b. GTP
c. UTP
d. CTP
e. TTP

UTP

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Glycogenin activity is necessary for the
a. synthesis of the oligo-glucose primer in glycogen synthesis
b. linear addition of glucose molecules to polysaccharide chains
c. degradation of glycogen to glucose 1-phosphate
d. introduction of the α1-6 branches into the glycogen granule

d. introduction of the α1-6 branches into the glycogen granule

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The activity of glycogen phosphorylase is regulated by phosphorylation. This is an example of
a. Competitive inhibition
b. Covalent modification
c. Feedback inhibition
d. Hormonal control
e. Allosteric activation

Covalent modification

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In the liver, glucose is an allosteric regulator of glycogen phosphorylase. This allows _(choose all that apply)
a. glycogen degradation to cease when glucose levels are high

b. glycogen synthesis to increase when glucose levels are high

c. glycogen degradation to increase when glucose levels are low

d. glycogen synthesis to increase when glucose levels are low

glycogen degradation to cease when glucose levels are high

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Sigmoidal activity plots of enzymes are usually associated with

a. Allosteric modification
b. Competitive inhibition
c. Covalent modification
d. Sequestration of the enzyme in alternative cell compartments
e. UDP addition to regulate substrate specificity

Allosteric modification

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Glycogen phosphorylase activity is regulated by all of the following mechanisms EXCEPT
a. allosteric modification
b. hormonal regulation
c. covalent modification
d. sequestration into alternate membrane bound organelles

sequestration into alternate membrane bound organelles

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cAMP binding to G-protein activates a(n)
a. enzyme cascade that enhances a regulatory signal

b. enzyme cascade that transfers a regulatory signal

c. catalyst that activates a substrate

d. inhibitor of signal transduction

enzyme cascade that transfers a regulatory signal

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In the muscle, glycogen phosphorylase is activated by
a. Mg2+ and ATP
b. Ca2+ and AMP
c. fructose-2,6-bisphosphate and citrate
d. AMP and glucose
e. AMP and acetylCoA

b. Ca2+ and AMP

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A sigmoidal enzyme activity curve indicates that the enzyme is probably (select all that apply):
a. a multimeric protein
b. regulated allosterically
c. subject to feedback inhibition
d. regulated by competitive inhibition
e. temperature sensitive

a. multimeric protein
b. regulated alllosterically
c. subject to feedback inhibition
d. regulated by competative inhibition

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Glycogen degradation is induced when (select all that apply):
a. Insulin levels are high
b. Blood glucose is low
c. Lactate concentrations are low
d. The body is at rest
e. Muscle activity is high

b. Blood glucose is low
c. Lactate concentrations are low

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What are the two activities of the debranching enzyme?

Transferase activity
Glycosylase activity

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Would you expect to find the gluconeogenesis-related enzyme glucose6Pase in the muscle cell? Explain

NO –> glucose is not exported from the muscle. They break down glycogen to glucose-6-phosphate to burn it themselves thru glycolysis
* Glucose-6-phosphatase is an enzyme that removes phosphate group from glucose-6-phosphate allowing free glucose to be released into blood
* Only liver expresses G6P b/c livers job to regulate blood sugar levels

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You have been hiking in the Wallowa mountains and have not eaten for several hours. Describe the sequence of events (metabolic pathways) that assure that your blood glucose does not dip below 5 mM

1. **Glycogenolysis** (breakdown of stored glycogen for glucose) 2. **Gluconeogenesis** (synthesis of glucose from non-carbohydrate sources) 3. **Lipolysis and Ketogenesis** (use of fats and ketones for energy) 4. **Hormonal regulation** (glucagon release to increase blood glucose) 5. **Muscle and tissue adaptation** to preserve glucose 6. Continuous monitoring and feedback to maintain blood glucose above 5mM. | **explained more on different document

Different tissues contain different signal receptors. For example, liver cells have receptors for glucagon and epinephrine whereas muscle cells only have receptors for epinephrine. Explain why this might make metabolic sense. | **explained more on different document

Epinephrin (from vigerous muscle activity) and glucagon (starvation in the liver) trigger phosphorylation of phosphorylase b (less active) to phosphorylase a (more active) so more glucose is needed.

Explain how glucose6P released during glycogen degradation can cross the hepatocyte membrane to enter the blood

- The catalytic site of glucose-6-phosphatase faces the lumen of the ER - A glucose 6-phosphate (G6P) transported (T1) carries the substrate from cytosol to the lumenm where glucose 6-phosphatase releases Pi. - The products (glucose and Pi) pass to the cytosol on specific transporters (T2 and T3). - Glucose leaves the cell via GLUT2 transporter in the plasma membrane | **explained further in separate document

**When glucose levels are high, glycogen phosphorylase should be** a. Sequestered b. Unaffected c. activated d. inactivated

d. inactivated

**Glucose acts as a regulator for glycogen phosphorylase. Choose the correct one for each pair of characteristics.** Negative / Positive Allosteric / Covalent Heterotrophic / Homotrophic

**negative** (glucose inhibits glycogen phosphorylase) **allosteric** (glucose binds to a site other than the active site) **heterotropic** (glucose is different from the substrate glycogen phosphorylase normally acts on)

Glycogen phosphorylase in the liver serves as a sensor for glucose levels. Explain how glucose regulates the activity of this enzyme

1. Glucose binding to an allosterically (not at active site) to **phosporylase a** form (active, phosphorylated form) 2. This causes a conformational change that exposes its phosphorylated Ser residues to the action of phophoprotein phosphatase 1 (PP1) 3. This phosphatase converts phosphorylase a to phosphorylase b --> sharply reducing the activity of phosphorylase and slowing the glycogen breakdown in response to high blood glucose. 4. Insulin also acts indirectly to stimulate PP1 and slow glycogen breakdown

What is the effect of GSK3 on glycogen synthase? _______________

**inhibits glycogen synthase** (*phosphorylates* glycogen synthase, which inactivates it)

What is the effect of insulin on glycogen synthase? How does this signal progress?

**Insulin activates glycogen synthase** (promotes glycogen synthesis) 1. Insulin binds to its receptor on the cell surface (tyrosine kinase) 2. Triggers a signaling cascade that activates protein phosphatase-1 (PP1) 3. PP1 depohosphorylates glycogen synthase, which activates glycogen synthase 4. At the same time, insulin signaling inhibits GSK3 (the enzyme that would otherwise inactivate glycogen synthase by phosphorylation) 5. Result = glycogen stays active --> glucose is stored as glycogen

What is the function of CKII (casein kinase II)?

- Phosphorylates glycogen synthase at specific sites - primes glycogen synthase for inhibition

Explain the effect of glucagon on glycogen synthase

Glucagon inhibits glycogen synthase - glucagon released when blood sugar is low - binds to receptors (mainly on liver cells), activating a signaling pathway involving cAMP and protein kinase A (PKA) - PKA phosphorylates glycogen synthase = inactivates it - As a result, glycogen synthesis stops (liver doesn't store glucose, releases glucose to raise blood sugar instead) | Glucagon -> activates PKA -> phosphorylates glycogen synthase -> inactiv

Erythrocytes run glycolysis, just like all other cells. Glucose enters erythrocytes from the blood via **facilitated diffusion / active transport**. Why is the activity of hexokinase required for this transport to function?

faciliated diffusion

**After eating a bowl of ice cream, what will happen to the blood sugar levels of a lactase-deficient (lactose-intolerant) individual?** a. Blood lactose levels will increase b. Blood glucose levels will decrease c. Blood galactose levels will increase d. Blood glucose levels will stay about the same

d. Blood glucose levels will stay about the same

After eating a loaf of bread, blood glucose levels are elevated. This induces **glucagon / insulin** signaling in the body, which promotes the fusion of GLUT 4 transporters to the cell membrane in the **muscle / liver**. This signaling also activates a cascade that activates** glycolysis /gluconeogenesis** via **FBPase-1 / PFK-2** in the **muscle / liver**.

* insulin * muscle * FBPase-1 * Liver

**Which of these enzymes would you expect to be active during an anaerobic “sprint” in the muscles? Select all that apply** a. Glucose-6-phosphatase b. Phospho-fructo-kinase 2 c. Lactate dehydrogenase d. Pyruvate dehydrogenase

* Lactate dehydrogenase * Phospho-fructo-kinase 2

**While you are sleeping, your body is under fasting conditions. What is true under these conditions?** a. Epinephrine signals the release of glucose from the liver b. Glucagon signals the breakdown of glycogen in the liver c. Insulin signals the uptake of glucose by the muscles d. Glucagon signals the synthesis of glycogen in the muscles

* Glucagon signals the brrakdown of glycogen in the liver

**During aerobic exercise (such as a light jog), which of these pathways would you expect to be active? Select all that apply and provide and explanation.** a. Glycolysis b. The Cori cycle c. Glycogen degradation d. Glycogenesis e. The Krebs cycle/TCA cycle f. Gluconeogenesis

a. **Glycolysis** (break down glucose -> pyruvate for energy. Glycolysis always active when muscles are working- even if O2 available) c. **Glycogen degradation**(break down muscle glycogen to supply glucose for glycolysis) e. **Krebs/TCA** cycle (pyruvate from glycolysis gets converted to acetyl-CoA, which enters TCA cycle to generate ATP aerobically)

**After muscle cells deplete their short-term glycogen stores, they can acquire more glucose via:** a. Gluconeogenesis b. Their long-term glycogen stores c. The liver’s glycogen stores d. They do not acquire new glucose; they only ferment pyruvate

c. Liver's glycogen stores (muscles cannot perform gluconeogenesis themselves)

**Glycogenolysis (glycogen degradation) releases a form of glucose that cannot enter glycolysis.Which enzyme transforms the first breakdown product into a form of glucose that can enter glycolysis?** A. Glycogen phosphorylase B. Phosphoglucomutase C. NDP-sugar pyrophosphorylase D. Transglycosylase E. Glycogenin

B. Phosphoglucomutase * glycogenolysis - breakdown of glycogen - released glucose-1-phosphate as the first product, but glucose-1-phosphate cannot directly enter glycolysis. * Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate * Glucose-6-phosphate can enter glycolysis

Which form of glucose can enter glycolysis to produce ATP?

glucose-6-phosphate

**Predict under which circumstances the enzyme glucose-6Pase is active in the muscle?** A. During starvation to provide glucose to the brain B. When glucose is plentiful C. Never, since glucose is not exported from the muscle D. When the liver need glucose 14

C: never In muscle cells, glucose-6-phosphate is used for energy production (via glycolysis) or stored as glycogen. Since muscle cells do not release glucose into the bloodstream, they lack glucose-6-phosphatase. Therefore, muscle cells do not convert glucose-6-phosphate back to glucose for export.

What is the role of glucose-6-phosphate?

Glucose-6-phosphatase is responsible for converting glucose-6-phosphate (G6P) into free glucose. This process happens in the liver and kidneys, where glucose is released into the bloodstream to maintain blood sugar levels, especially during fasting or starvation.

**Which nucleotide is required for glycogen synthesis?** A. ATP B. UTP C. CTP D. GTP E. cAMP

UTP Uridine triphosphate (UTP) reacts with glucose-1-phosphate (formed from phosphoglucomutase reaction with glucose-6-phosphate) --> glucose-1-p reacts with UDP-glucose pyrophosphorylase to form UDP-glucose and PPi The formed PPi is immediately hydrolyzed into Pi to form ATP which makes the reaction very favorable

**Glycogenesis (glycogen synthesis)** A. Begins with the reactions of glycogenin which produces the primer B. Involves the action of glycogen debranching enzyme. C. Involves transfer of glucose from CDP-glucose to a nonreducing end of a glycogen chain. D. Only occurs in the liver and muscle

**Glycogen phosphorylase a is regulated by phosphorylation. This covalent modification regulates the enzyme’s activity but does not completely inhibit it. The velocity plot of the enzyme is sigmoidal. What statement can be made about this enzyme?** A. It likely follows a Michaelis-Menten kinetic. B. Its reaction mechanism is likely exergonic. C. Its reaction mechanism includes covalent catalysis. D. It is probably an allosteric enzyme. Glycogen phosphorylase a is regulated by phosphorylation. This covalent modification regulates the enzyme’s activity but does not completely inhibit it.

What 3 enzymes are involved in the degradation of glycogen?

- Glycogen phosphorykase - Glycogen debranching enzyme - Phosphoglucomutase

What is the product of the reaction of glycogen phosphorylase?

Glucose-1-phosphate

**A G-protein coupled receptor binds its ligand, activating a heterotrimeric G-protein that stimulates a two-fold increase in cAMP. What is the end result on carbohydrate metabolism of the glycagon/epinephrine induced enzyme cascade via cAMP?** A. They increase glycogen synthesis. B. They increase gluconeogenesis and decrease glycolysis. C. They inhibit hexokinase, especially in liver and muscle. D. They activate anaerobic metabolic pathways. E. They increase blood glucose concentration

E The rise in [cAMP] activates cAMP-dependent protein kinase, also called protein kinase A (PKA). PKA then phosphorylates and activates phosphorylase b kinase, which catalyzes the phosphorylation of glycogen phosphorylase b, activating it (into its form phosphorylase a) which stimulates glycogen breakdown.

**Glycogen synthase kinase 3 (GSK3)** A. functions only in regulation of glycogen synthase. B. phosphorylates glycogen synthase only after glycogen synthase has been phosphorylated by another kinase. C. is directly stimulated by insulin. D. phosphorylates casein kinase II.

B First needs to be phosphorylated by CKII in an event called priming.

**Which enzyme involved in glycogenesis and glycogenolysis is allosterically regulated?** A. glycogen phosphorylase B. glycogen synthase C. phosphoprotein phosphatase 1 (PP1) D. All of the answers are correct.

D In the liver, glucose acts allosterically to make phosphorylase a more susceptible to dephosphorylation/inactivation by phosphoproteinPP1. Glucose 6-phosphate allosterically activates PP1. Glycogen synthase is inactive unless its allosteric activator, glucose 6-phosphate, is present.

**Which statement describes a major difference between muscle and liver glucose regulation?** A. Muscle uses stored glycogen only for its own needs. B. During exercise, muscle undergoes very large changes in need of ATP. C. Muscle lacks the enzyme machinery for gluconeogenesis. D. Muscle cells lack a receptor for glucagon. E. All of the answers are correct

When glycogen synthase is phosphorylated, glycogen phosphorylase is...

Phosphorylated

Low blood glucose increases / decreases the breakdown of glycogen and increases / decreases the rate of glycogen synthesis. We would expect enzymes like PKA and glycogen phosphorylase to be active / inactive. The presence of glucagon would be increased / decreased, and the presence of insulin would be increased / decreased. This will overall increase / decrease the rate of glycolysis.

**Glycogen synthase (GS) is activated by phosphorylation via glycogen synthase kinase 3 (GSK3). However, GSK3 needs** a. a priming phosphorylation by casein kinase II (CKII) to add the initial phosphate to GS b. an initial phosphorylation of the GSK3 active site c. to be transported to the nucleus for activation by CKII d. allosteric binding by Ca2+ to become active

b. an initial phosphorylation of the GSK3 active site

**Which of these conditions is associated with glycogen synthesis in the muscle? Select all that apply.** a. Insulin b. Epinephrine c. Glucagon d. Active glycogen phosphorylase e. Active glycogen synthase f. Glucose-6-phosphate

a. insulin e. Active glycogen synthase f. Glucose-6-phosphate

**During aerobic exercise (such as a light jog) which of these pathways would you expect to be active? Select all that apply.** a. Glycolysis b. The Cori cycle c. Glycogen degradation d. Glycogenesis e. The Krebs cycle/TCA cycle f. Gluconeogenesis

a. Glycolysis e. Krebs cycle/TCA cycle

**Why are muscle and liver glycogen phosphorylase regulated differently?** A. Muscle only consumes glucose, and liver both consumes and secretes glucose. B. They are isozymes and are encoded by different genes. C. Muscle and liver have different glucose transporters. D. Muscle has no glycogen phosphorylase a isoform. E. Liver has no glycogen phosphorylase kinase.

A Glycogen stores in myocytes and liver have different roles. In myocytes phosphorylase supplies glucose for the tissue's own needs. In the liver phosphorylase supplies glucose to the blood for use by other tissues.

Ch 15 - Glycogen metabolism Flashcards

(60 cards)