Section 3: Glycogen Synthesis

What does UDP-Glucose Pyrophosphorylase activate

• It activates glucosyl units

  • takes glucose and activates it

What does glycogen synthase extend

• Extends glycogen chains

  • we need to have an existing glycogen primer to synthesize

What does glycogen branching enzyme transfer

Transfers seven-residue glycogen segments

Glycogen Synthesis & Degradation image

Is glycogen synthesis from G1P thermodynamically favorable or nonfavorable

Thermodynamically unfavorable

What are three enzymes that participate in glycogen synthesis

1. UDP-glucose pyrophosphorylase

2. glycogen synthase

3. glycogen branching enzyme

Describe UDP-Glucose Pyrophosphorylase function

• It activates glucosyl units

  • Uridine diphosphate glucose (UDPG)

• UDPG is “activated” compound

  • it can donate a glucosyl unit to the growing glycogen chain

• Formation of UDPG itself has ‘∆G˚’ = 0

What makes UDP-glucose pyrophosphorylase exergonic

Subsequent exergonic hydrolysis of PP_i by inorganic pyrophosphatase makes the overall reaction exergonic

What is the overall equation for UDP-glucose pryophosphorylase

UDP-Glucose Pyrophosphorylase reaction

Describe glycogen synthase function

• Extends glycogen chains

• It transfers glucosyl unit of UDPG to C4-OH group on one of glycogen’s non-reducing ends to form an α(1→4) glycosidic bond

• The ‘∆G˚’ for the glycogen synthase reaction is -13.4 kJ • mol^-1

Glycogen synthase reaction

Is glycogen synthase spontaneous or nonspontanoues

Spontaneoues

Describe how glycogen synthesis has an energetic price

• We have to put in energy that comes from UTP

  • UTP is the energy we require to activate our glucose unit before we can incorporate it into our glycogen

• 1 UTP is cleaved to UDP for each glucose residue incorporated into glycogen

• UTP is replenished using ATP as substrate through a phosphoryl-transfer reaction mediated by nucleoside diphosphate kinase

• UTP consumption is energetically equivalent to ATP consumption

Can glycogen synthase simply link 2 glycose residues together ?

NO! it can ONLY extend already existing α(1→4)-linked glucan chain

What is the 1st step in glycogen synthesis

Glycogenin acts as glycosyltransferase

— it attaches glucose residue donated by UDPG to OH group of its Tyr 194

What is the importance of glycogenin

• Glycogenin is responsible for building up initial glycogen

• Glycogenin extends the glucose chain by up to 7 additional UDPG-donated glucose residues

• Formation a glycogen “primer”

  • W/ a primer, only then do we see the activity of our glycogen synthase

• Glycogen synthase commence is extending the primer

Each glycogen molecule associated w/ …

• 1 molecule glycogenin

  • Responsible for initial glycogen primer composed up to 6 glucose subunits

• 1 molecule glycogen synthase

  • adds on to the primer

Describe the function of glycogen branching enzyme

• Transfers 7-residue glycogen segments

  • glycogen synthase generates only α-amylose

    • This would only allow to release one glucose molecule at a time

• Branching by amylo-(1,4→1,6)-transglycosylase (branching enzyme) distinct from glycogen debranching enzyme

• A branch is created byy transferring a 7-residue segment from chain end to C6-OH grpup of a glucose residue on the same or another glycogen chain

• Each transferred segment must come from a chain of at least 11 residues

How many residues are between 2 branches

4 resiudes

Branching pattern of glycogen has been optimized by evolution for the …

… efficient storage and mobilization of glucose