Glycogen Synthesis

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Glycogen Synthesis
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Topics Glycogen Synthesis

• Glycogen convenient condensed energy source
• Glycogen synthesis pathway
• Tissue differences in glycogen synthesis

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Why store fuel as Glycogen rather than Fat?

• Fat is not mobilized as quickly
• Fat cannot provide energy under anaerobic
  conditions
• Fat cannot (easily?) be converted to glucose to
  buffer blood glucose (brain/neurons)

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Why not store glucose monomer?

• Same amount of reserve would require 0.4 M
  glucose in cells! Cells would burst from osmotic
  pressure
• Reserve in glycogenintracellular is only 0.01
  uM, Causing no osmotic pressure problem

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Glycogen Facts.

• A branched-chain of D-glucose
• 400 g glycogen in resting muscle
• (1-2 wet weight)
• 100 g glycogen in fed liver
• (6-8 wet weight)
• Single glycogen molecule up to 100,000,000 Da
• Exists as granules in cell cytoplasm. Granule
  contains enzymes for both glycogenesis
  glycogenolysis

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Gluconeogenesis can feed into synthesis of
glycogen
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Glycogen synthesis pathway
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Overall glycogen synthesis
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• Steps
• Isomerization G6P -gt G1P
• Activation by UTP
• Glycogenin priming
• Extension by Glycogen Synthase
• Branching
• Repeat 4 5

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The enzymes
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Reactions of glycogen synthesis

• Investment of
• 1 mole UTP
• 1 mole ATP

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Activation of glucose by UTP is necessary for
synthetic reactions
1 mole of ATP invested
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Reaction is driven by subsequent hydrolysis of
pyrophosphate
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Glycogen Synthase reaction
can make 1-gt4 but not 1-gt6 (branch) linkages
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The branching reaction

• Glycosyl-transferase moves a large linear
  chunk to a branch position (C6)
• Increases density of polymer
• Increases solubility of polymer (e.g vs.
  cellulose)

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Tissue differences in glycogen synthesis
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Glycogen serves different purposes in liver and
muscle
Liver blood sugar buffering (free glucose is
made, exported) Muscle stored fuel (no free
glucose intermediate G6P is used)
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Muscle fibers synthesize and store glycogen
during inactivity

• During activity uses
• free glucose
• stored glycogen
• glucose from the liver (mobilized glycogen)

Fasting does NOT deplete muscle glycogen for
many weeks, whereas exercise depletes it in
hours!
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Brain cells/neurons do not store glycogen
Get glucose from the liver glycogen
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Liver responds to high blood glucose by
synthesizing glycogen
Exports glucose to brain, muscle, RBCs Liver
glycogen is depleted during a fast (gt 24
h) Purpose of glycogen is for blood glucose
buffering
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Glycogen synthesis and degradation are regulated
by enzyme phosphorylation(Insulin vs. Glucagon)
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liver
muscle
Insulin signalling pathway stimulates glycogen
synthesis in both muscle and liver cells
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• You should know
• Advantages of glycogen as a stored fuel source
• Reactions of glycogen synthesis
• Roles of key enzymes involved
• How tissues differ in synthesis and utilization