Glycogen Metabolism and Its Regulation in Biochemistry 440, Fall 2008 - Prof. Rachel Klevi, Study notes of Biochemistry

Information on glycogen, its structure, metabolism, and regulation in the context of biochemistry 440, fall 2008 lecture 20. Topics include the role of glycogen as a short-term glucose storage form, its polymer structure, and the enzymes involved in glycogen breakdown and synthesis. The document also discusses the thermodynamics of glycogen metabolism and glycogen storage diseases.

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Biochemistry 440, Fall, 2008 Lecture 20
1
Glycogen Metabolism
and its regulation
Reading assignment:
Chapter 15.4-15.5: p. 594-604 (605-609 optional)
2
Lecture 20
Glycogen
• Storage form (short-term) of glucose in vertebrates
and many microbes (starch in plants)
• Mainly formed in liver and muscle to provide a
quick source of energy
• Glycogen in liver is a reservoir for other tissues
during fast (brain, muscles)
• polymer of α-D-glucose
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Glycogen Metabolism

and its regulation

Reading assignment:

Chapter 15.4-15.5: p. 594-604 (605-609 optional)

Lecture (^202)

Glycogen

• Storage form (short-term) of glucose in vertebrates

and many microbes (starch in plants)

• Mainly formed in liver and muscle to provide a

quick source of energy

• Glycogen in liver is a reservoir for other tissues

during fast (brain, muscles)

• polymer of α-D-glucose

Lecture (^203)

Structure of Glycogen

O

OH

OH

OH

OH

CH 2 OH

O

OH

OH

OH

OH

CH 2 OH

O

Most linkages in glycogen are α(1 --> 4)

Lecture (^204)

Structure of Glycogen

 1/10 of the linkages are α(1 --> 6).

O

OH

OH

OH

OH

CH 2 OH

O

OH

OH

OH

OH

CH 2 OH

O

H

Glycogen

breakdown

Figure 15-26 (^) ( α Unbranched1->4) polymer

Nonreducing ends

( α 1->4)

Lecture (^208)

O

OH

OH

OH

CH 2 OH

O

OH

OH

CH 2 OH

O O

O

OH

OH

CH 2 OH

O

O

OPO 3 2-

OH

OH

OH

CH 2 OH

Glucose 1P

O

OH

OH

OH

OH

CH 2 OPO 32 -

Glucose 6P

pyruvate

glycolysis

Glycogen breakdown - phosphorolysis

Lecture (^209)

Glycogen Breakdown

 What would be the product if the

α(1--->4) bonds were broken by hydrolysis

(i.e. if the bonds were attacked by H 2 O

instead of Pi)?

 Would this be as effective a use of glycogen

as an energy source?

Lecture (^2010)

O

OH

OH

OH

CH 2 OH

O

OH

OH

CH 2 OH

O O

O

OH

OH

CH 2

O

OH

OH

CH 2 OH

O

OH

OH

CH 2 OH

O O

O

OH

OH

CH 2 OH

O

Glycogen Debranching Enzyme

Lecture (^2013)

Thermodynamics of Glycogen Metabolism

 Glycogenn+1 + Pi --> Glycogenn + G 1-phosphate

 ΔG’^0 of the phosphorylase reaction is

+3.1 kJ/mole.

In the cell, the ratio of [G1P]/[Pi] ranges from

1/30 to 1/100, so this step is exergonic.

(Q < Keq)

==> Glycogen synthesis is NOT the

reverse of glycogen breakdown!

Lecture (^2014)

Comparison of

Breakdown and Synthesis

 Breakdown:

Glycogenn+1 + Pi -> glycogenn + Glucose 1-phosphate

 Synthesis:

 Glucose 1-phosphate + UTP ---> glucose-UDP + PPi

 PPi + H 2 O --> 2 Pi

 Glycogenn + UDP-glucose --> glycogenn+1 + UDP

Lecture (^2015)

Glycogen synthesis

 UDP-glucose is made

 Glucose is transferred from UDP-glucose

to glycogen

-> making (α1-->4) linkages

 α(1-->6) linkages are introduced

-> making branches

Lecture (^2016)

Synthesis of UDP-glucose

 G1P + UTP ---> glucose-UDP + PPi

 ΔG’^0 = ~ 0 kJ/mol

 PPi + H 2 O --> 2Pi

 ΔG’^0 = -25 kJ/mol

Lecture (^2019)

Glycogen Storage Diseases

 9 different types.

 VII: Lack PFK in muscle.

 I: lack of glucose 6-phosphatase, affects

gluconeogenesis and glycogen storage

 III: lack of debranching enzyme.

 IV: lack of branching enzyme.

Lecture (^2020)

Regulation of Glycogen Metabolism

 Phosphorylase is activated by

phosphorylation

-> regulated by hormonal control

 Glycogen synthase is INactivated by

phosphorylation

Figure 15-

Lecture (^2022)

Glycogen phosphorylase in liver

Figure 15-