Glycogen Regulation (Ben) Flashcards

1
Q

What two main enzymes control glycogen metabolism?

And VERY generally what activates/deactivates them?

A
  • Glycogen Synthase - deactivated by phosphorylation
  • Glycogen Phosphorylase - activated by phosphorylation
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2
Q

What common signalling molecule increases phosphorylation of glycogen regulating enzymes?

A

cAMP

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3
Q

How is cAMP formed?

And via what hormonal messengers?

A

cAMP is formed from ATP via adenylyl cyclase (producing also PPi)

  • Glucagon, Epinephrine, Norepinephrine all stimulate cAMP synthesis
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4
Q

How is cAMP broken down?

Into what?

A

Phosphodiesterase

  • breaks cAMP down into 5’ AMP
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5
Q

What hormone stimulates cAMP breakdown?

And what other hormones’ effects are thereby inhibited?

A
  • stimulated by insulin in the liver
  • stops the [cAMP] increase —> phosphorylation-increasing effects of nor-/epinephrine and glucagon
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6
Q

What enzyme catalyzes activation of the main glycogenolysis-performing enzyme?

How?

A

Phosphorylase Kinase

  • phosphorylates inactive Phosphorylase B into active Phosphorylase A
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7
Q

What 2 things allosterically inhibit the main glycogen breakdown enzyme in both liver and muscle tissue?

A

ATP + Glucose-6-phosphate both inhibit active Phosphorylase A

  • because both indicate plenty of free, usable energy in the cell and no need for glycogenolysis
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8
Q

What allosteric effector molecule binds only to muscle-type phosphorylase?

How does it effect the enzyme?

A

5’ AMP binds to muscle phosphorylase

  • it activates the inactive phosphorylase b
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9
Q

How is 5’ AMP formed (enzyme + products)?

What does an increase in its concentration indicate?

A
  • formed when increased [ADP] is altered by Adenylate Kinase to form ATP and 5’AMP
  • it indicates a need for increased substrate metabolism (and thus activates glycogenolysis to free up glucose) for ATP formation
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10
Q

What is the regulatory chain of events leading to glycogenolysis, starting from hormonal messengers?

A
  1. Glucagon (liver, due to low [Glc]) Norepinephrine (muscle)
  2. Increase in concentration of cAMP
  3. Activation of cAMP-Dependent Protein Kinase (PKA)
  4. Phosphorylation of Phosphorylase Kinase > A form
  5. Phosphorylation of Phosphorylase B > A form
  6. Glycogenolysis
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11
Q

How are muscle contraction and glycogenolysis synchronized?

A

Ca2+

  • increased intracellular [Ca++] during contraction also activates muscular phosphorylase kinase
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12
Q

How does Ca++ activate glycogenolysis?

(Including info about the structure of the enzyme it affects.)

A

Phosphorylase kinase is a tetramer:

Subunits:

  • Alpha/Beta: Serinesphosphorylated byPKA
  • Delta: Calmodulin - binds 4 Ca++ + activates gamma
  • Gamma: Catalytic site
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13
Q

How does cAMP-independent glycogenolysis work and in what tissue?

Start with the receptor…

A

Alpha-1 Adrenergic Receptors in the liver

  • activated by nor-/epinephrine
  • activate Gq > IP3 ^ > ER Ca++ release
  • activation of Phosphorylase Kinase, etc.
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14
Q

What other (non-adrenergic) hormones activate cAMP-independent glycogenolysis?

A
  • Vasopressin
  • Oxytocin
  • Angiotensin II
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15
Q

What enzyme can inactivate both phosphorylase + phosphorylase kinase?

How?

A

Protein Phosphatase-1

  • dephosphorylates both enzymes to inhibit glycogenolysis
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16
Q

What specifically inhibits protein phosphatase-1 and how is it activated?

Why is its activation unique?

A

Inhibitor-1

  • activated by PKA
  • PKA therefore controls both activation and inhibition of phosphorlyase
17
Q

What hormone reinforces the effect of protein phosphatase-1 and how?

A

Insulin

  • increases glucose uptake thereby increasing [G6P] which inhibits phosphorylase kinase
18
Q

Generally, how is glycogen synthase activated/inactivated?

What does this mean for the effect of the following molecules on it….

Phosphorylase Kinase?

PKA?

Insulin?

Protein phosphatase-1?

A

Dephosphorylation activates glycogen synthase, so…

  • Phosphorylase Kinase: phosphorylates + deactivates
  • PKA: phosphorylates + deactivates
  • Insulin: Raises G-6-P, stimulates dephosphorylation + activates
  • Protein Phosphatase-1: Dephosphorylates + Activates