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SMP - MNE Exam 2 > Lecture 21: Glycogen Coordination & Fuel Metabolism > Flashcards

Lecture 21: Glycogen Coordination & Fuel Metabolism Flashcards

1
Q

Can the brain use fats for fuel? Why/Why not?

A

Only very few FAs can cross the BB (essential ones like omega-3 and 6s), but even then they are too slow to be a steady supply for the brain

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2
Q

Are ketone bodies hydrophilic or hydrophobic?

A

Hydrophilic (very negative!)

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3
Q

Which are more oxidized: fats or proteins?

A

Proteins

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4
Q

How much more energy does fat provide compared to glycogen?

A

6x the metabolic energy

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5
Q

Why do the high levels of blood glucose in diabetes cause damage to vascular and neurological systems?

A

Because glucose can be deprotonated and act as a Nu attacker on various macromolecules like collagen

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6
Q

What is the maintained physiological concentration of blood glucose?

A

5 mM = 100 mg/100ml

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7
Q

Why can’t glucose be stored as is in cells?

A

Because it’s very hydrophilic and individual molecules attain entropy so it would pull water into the cells which would then lyse

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8
Q

Describe glycogen’s structure.

A

α-1,4 glycosidic bonds with branching α-1,6 linkages every 8-10 residues

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9
Q

What is the purpose of glycogen’s branching?

A

To increase the number of non-reducing ends that are accessible for rapid glucose mobilization

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10
Q

How many glucose units does each glycogen granule include?

A

Up to 120,000

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11
Q

What % of skeletal muscle cell mass is comprised of glycogen?

A

0.5% on average

1-2% at most

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12
Q

What % of liver cell mass is comprised of glycogen?

A

4% on average

10% at most

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13
Q

Order of preferred heart metabolism?

A
  1. Aerobic FA metabolism
  2. Aerobic ketone bodies metabolism
  3. Aerobic glucose bodies metabolism
  4. Anaerobic glucose bodies metabolism
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14
Q

What are the 4 main purposes of glycogen?

A
  1. Glucose homeostasis
  2. Reduces osmotic pressure in the cell
  3. Rapid energy release
  4. Massive energy release thanks to many non-reducing ends
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15
Q

How does glycogen reduces osmotic pressure inside the cell?

A

By reducing the number of molecules of glucose floating around (osmotic pressure directly related to # of solutes)

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16
Q

What are the 2 molecules that starch is made of?

A
  1. Amylose

2. Amylopectin

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17
Q

Describe the structure of amylose

A

α-1,4 linkages

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18
Q

Describe the structure of amylopectin

A

α-1,4 linkages and α-1,6 branching linkages every 24-30 residues

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19
Q

Why do potatoes go bad?

A

Because they are made of amylose which non-reducing ends are accessible to bacteria

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20
Q

What are 4 advantages of glycogen compared to TAGs?

A
  1. Faster mobilization and metabolism
  2. Both aerobic and anaerobic metabolisms are options
  3. Ability to maintain glycemic levels
  4. Cori cycle
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21
Q

What are 2 disadvantages of glycogen compared to TAGs?

A
  1. Limited storage quantity because glycogen is hygroscopic: it binds 3-4 times its weight in water
  2. Limited storage time
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22
Q

After how many hours of fasting are liver stores functionally depleted? Meaning they are not the main contributors to blood glucose levels

A

12 hrs

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23
Q

Describe the glycogenolysis pathway before the enzyme gets close to the branching. 4 steps

A
  1. Glycogen phosphorylase phosphorylates C1 = G1P
  2. Phosphoglucomutase (using Ser) = G6P
    3a. Glycolysis
    3b. IN LIVER: G6P transported to ER lumen by G6P transporter: G6P phosphatase = glucose + Pi
    4b. Glucose transported to cytosol by glucose transporter/Pi transported to cytosol by Pi transporter
    4c. Glucose exits cell via GLUT2
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24
Q

Why can’t glycosidic linkages simply be hydrolyzed to mobilize glucose?

A

Because the energy in the bond would be released and lost as heat

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25
Q

Which are the only 2 organs that have the enzyme G6P phosphatase? Why?

A

Liver and kidneys because only organs able to break down glycogen for glucose homeostasis and perform gluconeogenesis

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26
Q

Describe the glycogenolysis pathway when the enzyme gets close to the branching. When does this happen exactly? 2 steps

A

Once it reaches the 4th glucose from the branching point:

  1. Transferase activity of debranching enzyme: transfers 3 glucose from the branch and adds it to the non-reducing end of another chain
  2. Glucosidase activity of debranching enzyme: hydrolyzes α-1,6 branching linkage
27
Q

Which bonds have more energy: α-1,6 branching linkages or α-1,4 glycosidic linkages ?

A

α-1,4 glycosidic linkages

28
Q

Which enzyme is faster: glycogen phosphorylase or debranching enzyme?

A

Glycogen phosphorylase

29
Q

What is the rate-limiting step of glyceogenolysis?

A

The debranching

30
Q

Describe the pathway of adding glucose monomers to glycogen. 2 steps

A
  1. UDP-glucose phosphorylase: G1P (attacking Nu) + UTP = UDP-glucose + PPi (= P + P by pyrophosphatase)
  2. Glycogen synthase: UTP-glucose + C4 of non-reducing end of glycogen (Nu) = glycogen + UDP (=>UTP)
31
Q

What is the NTP usually used in glycogen synthesis? Which phosphoanydride bond is attacked?

A

UTP

The α one

32
Q

Describe the de novo glycogen synthesis pathway.

A

PRIMER SYNTHESIS catalyzed by glycogenin:

  1. Tyr residue attacks C1 of NDP-glucose (NDP released)
  2. Glucosyltransferase activity: (-OH) on C4 attacks C1 of another NDP-glucose (NDP released)
    - -> done until primer has 8-10 glucose

BRANCHING catalyzed by glycogen branching enzyme:
1. Straight-chain series cleaved off
2. Energy released from
α-1,4 bond used to make α-1,6 linkage and heat released

33
Q

Is glycogen branching enzyme regulated by hormones?

A

NOPE

34
Q

Describe the activation of glycogen phosphorylase.

A

Phosphorylase kinase phosphorylates glycogen phosphorylase b with 2 ATP = glycogen phosphorylase a + 2 ADP

35
Q

Describe the deactivation of glycogen phosphorylase.

A

Phosphoprotein phosphatase-1 (PP1) hydrolyzes the 2 phosphate groups on glycogen phosphorylase a with 2 H2O = glycogen phosphorylase b + 2 Pi

36
Q

What are the 4 stimulators of phosphorylase kinase in liver and muscle? How does each work?

A

LIVER:

  1. Glucagon (through PKA)
  2. Epinephrine (through PKA)

MUSCLES:

  1. Epinephrine (through PKA)
  2. Ca2+ (allosteric)
  3. AMP (allosteric)
37
Q

Describe the activation of phosphorylase kinase by glucagon/epi.

A

Protein kinase A (PKA) phosphorylates phosphorylase kinase b with 2 ATP = phosphorylase kinase a + 2 ADP

38
Q

Describe the deactivation of phosphorylase kinase.

A

Phosphoprotein phosphatase-1 (PP1) hydrolyzes the 2 phosphate groups on phosphorylase kinase a with 2 H2O = phosphorylase kinase b + 2 Pi

39
Q

How is PKA regulated?

A

Hormonally via cAMP -
activated by:
1. Glucagon
2. Epinephrine

40
Q

Describe the activation of glycogen synthase.

A

Phosphoprotein phosphatase-1 (PP1) hydrolyzes the 2 phosphate groups on glycogen synthase b with 2 H2O = glycogen synthase a + 2 Pi

41
Q

Describe the deactivation of glycogen synthase.

A

Glycogen synthase kinase-3 (GSK-3) using 3 ATP/PKA using 1 ATP/CKII using 1 ATP/phosphorylase kinase using 2 ATP, can ALL phosphorylate glycogen synthase a = phosphorylase kinase a + 2 ADP

42
Q

What inhibits GSK-3?

A

Insulin

43
Q

What is phosphoprotein phosphatase-1 (PP1) stimulated by? Explain the last 2

A
  1. Insulin
  2. G6P (from G1P broken down by glycogen phosphorylase)
  3. Glucose (from glucose broken down by debranching enzyme)
44
Q

What is dephosphorylation of glycogen synthase by phosphoprotein phosphatase-1 (PP1) inhibited by?

A
  1. Glucagon

2. Epinephrine

45
Q

What are the 3 fuels that skeletal muscle can use?

A
  1. Glucose
  2. FAs
  3. Ketone bodies
46
Q

Main fuel source of adipose tissue?

A

Glucose

47
Q

Where are FAs mainly synthesized?

A

The liver

48
Q

At what glucose blood concentration does neural dysfunction occur?

A

Below 2.5 mM

49
Q

What fuel does the liver use?

A

α-Ketoacids

50
Q

How does the liver avoid using glucose? What other purpose does this serve?

A

It uses glucokinase (hexokinase 4) instead of hexokinase, which has a high Km and lowe Vmax, so it does not compete with other organs for glucose when glucose is low

Also allows prevention of glucose phosphorylation before it goes through GLUT2

51
Q

What is necessary to cross the BBB?

A

Hydrophilicity!

52
Q

What are the 2 places where we find glycogen?

A
  1. Muscles

2. Liver

53
Q

Can muscles break down glycogen for glucose homeostasis?

A

NOPE

54
Q

After how many hours are glycogen stores COMPLETELY depleted?

A

24 hrs

55
Q

After how long are the muscle glycogen stores depleted?

A

Depends on level activity, but after enough starvation hours it’s broken down so that the lactate can be converted to alanine for gluconeogenesis

56
Q

Which phosphate linkage contains more energy: G1P or G6P?

A

G1P

57
Q

Is the conversion of G1P to G6P reversible? Why?

A

Yes because the difference in energy between G1P and G6P is small

58
Q

How much of the muscle glycogen can be RAPIDLY mobilized?

A

About 50% before branching

59
Q

Why does debranching enzyme transfer a triose and then hydrolyze the 1,6 bond instead of debranching the whole 4 glucose?

A

Thermodynamics: alpha 1,4 bonds contain more energy than alpha 1,6 so it would be endothermic to cleave the 1,6 to form a new 1,4 bond

60
Q

Is energy released or consumed to make glycogen 1->4 linkages? How is this made up for in skeletal muscle?

A

Consumed but made up in skeletal muscle because the first step of glycolysis will be bypassed (usually uses 1 ATP)

61
Q

What are the non-reducing ends?

A

(-OH) at C4

62
Q

Is the conversion of G1P by G6P by phosphoglucomutase reversible?

A

YUP

63
Q

What is good about using glycogen to make G6P for entry into glycolysis?

A

We bypass the first step of glycolysis, thereby saving energy

SMP - MNE Exam 2 (17 decks)

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