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1. GLYCOGENOLYSIS
Glycogenolysis: Glycogen and Reactions of Glycogenolysis Medical Editor: Jona Frondoso

OUTLINE III) REACTIONS OF GLYCOGENOLYSIS

I) INTRODUCTION Location: cytosol [Harvey & Ferrier, 2011]

II) GLYCOGEN
III) REACTIONS OF GLYCOGENOLYSIS
IV) APPENDIX (A) STEP 1: PHOSPHOROLYSIS
V) REVIEW QUESTIONS Glucose molecules are removed from the glycogen chain
(Figure 2)
I) INTRODUCTION Glucose molecules are phosphorylated by glycogen
phosphorylase at α-1,4 glycosidic bond until only four
Glycogen is broken down to glucose (opposite of glucose residues remain bonded to the main chain.
glycogenesis) o Not capable of cleaving beyong the fourth glucose
(1) Two main organs of glycogenesis residue
o Cofactor: pyridoxal phosphate (derivative of Vitamin
Liver B6)
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Muscle – only up to a certain point
Reaction yields glucose-1-phosphate (G1P)
(2) Glycogenesis occurs during Fasting state o At least five G1P are formed
↓ Blood glucose levels (hypoglycemia)
o Not pathological
o Still within normal glucose levels (80-120 mg/dL)
Enough to trigger the production of the following
hormones:
o Glucagon
o Epinephrine (Epi)
o Norepinephrine (NE)
o Growth hormone (GH)

II) GLYCOGEN
Glycogenin - base protein molecule that is holding on the Figure 2. Phosphorolysis of glucose at alpha-1,4-glycosidic
entire glycogen polymer bond.
Glycogen - Branched glucose polysaccharide composed
of chains of glucose units linked by α-1,4 bonds with α- (B) STEP 2: HYDROLYSIS
1,6 branches every 8-10 residues
(1) Debranching Enzyme (Figure 3)
Remember:
(i) α-1,4-glucosidase activity
General Structure of Glucose (Figure 1)
Cleaves the α-1,4 bonds of the remaining glucose
Very important to remember is the number of carbons. residues until only one glucose remains bonded to the
Carbons are numbered from 1 to 6 main chain
Carbon 1 (C1) = carbonyl (-COOH) C = reducing end
Carbon 4 (C4) = non-reducing end (ii) 3-glucose transfer
Throughout the lecture notes, glucose will be
represented by a circle for simplicity. Also takes three glucose molecules and transfers them to
the next glycogen chain

(iii) α-1,6 glycosidic bond activity

A debranching enzyme breaks α-1,6 glycosidic bonds so
branches of glucose molecules can be hydrolyzed by
reaction 1.
o Yields one free glucose
 Can go right out of the cell into the bloodstream,
increasing the blood glucose levels (insignificant
amounts)

Figure 1. Structure of glucose. [Nelson & Cox, 2005]

GLYCOGENOLYSIS METABOLISM: Note #1. 1 of 3

Figure 3. Alpha-1,4-glucosidase, 3-glucose transfer, and alpha-
1,6-glcyosidic bond activity of the debranching enzyme.

(C) STEP 3: ISOMERIZATION OF G1P TO G6P

Catalyzed by the reversible enzyme, Figure 5. Hydrolysis of G6P to glucose and the transport of the
free glucose to the blood.
phosphoglucomutase
Glucose-1-phosphate molecules are converted to
glucose-6-phosphate molecules that enter the glycolysis (1) Glucose-6-phosphatase
at reaction 2
Only found in the cells of:
o G6P – cannot be transported out of the liver
o Liver
o Kidney – specifically, the proximal convoluted tubule
o GIT – specifically, the duodenum
Absent in the muscle
o Can do glycogenolysis but does not have glucose-6-
phosphatase → Cannot release free glucose into the
blood
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Figure 4. Isomerization of G1P to G6P. o Get stuck at glucose-6-phosphate
o Utilizes an indirect mechanism to convert G6P to free
(D) STEP 4: DEPHOSPHORYLATION glucose – Cori Cycle and Glucose-Alanine Cycle
Brought into the smooth endoplasmic reticulum (SER) via
the GLUT (T1) transporter (Figure 5)
Glucose-6-phosphatase hydrolyzes the glucose-6-
phosphate to yield free glucose
Free glucose is transported out of the SER via GLUT (T2)
transporter, and finally out of the cell into the bloodstream

IV) APPENDIX

Figure 6. Overview of glycogenolysis.

2 of 3 METABOLISM: Note #1. GLYCOGENOLYSIS

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 Table 1. Summary of the Reactions in Glycogenolysis and the Enzymes Catalyzing Them
Reaction Enzyme
1. Phosphorolysis Glycogen phosphorylase
2. Hydrolysis Glycogen phosphorylase
3. Isomerization of G1P to G6P Phosphoglucomutase
4. Dephosphorylation Glucose-6-phosphatase

V) REVIEW QUESTIONS
Which of the following statements describe
glycogenolysis?
a. It is activated by low levels of blood glucose.
b. It converts glucose-6-phosphate to glucose-1-
phosphate
c. It is activated by high levels of glucose-6-phosphate
d. Glucose + UTP → UDP-glucose + PPi

Which of the following does not stimulate

glycogenolysis?
a. Norepinephrine
b. Growth hormone
c. Epinephrine
d. Insulin

Arrange the following statements sequentially:

1. Isomerization
2. Phosphorolysis
3. Hydrolysis
4. Dephosphorylation

a. 1-2-4-3
b. 2-3-1-4
c. 3-1-4-2
d. 4-3-2-1 AfraTafreeh.com
Which of the following statements about glucose-6-
phosphatase is correct?
a. Its substrate is glucose-1-phosphate
b. It is found in the liver kidney, and the GIT
c. It catalyzes a reaction that occurs in the rough
endoplasmic reticulum.
d. Its inactive form is present in the muscle.

CHECK YOUR ANSWERS

VI) REFERENCES

Harvey, R., & Ferrier, D. (2011). Lippincott's Illustrated

Reviews - Biochemistry (5th ed.). Philadelphia: Lippincott Williams &
WIlkins.
Nelson, D., & Cox, M. (2005). Lehninger Principles of
Biochemistry (4th ed.). New York: W.H. Freeman and Company.

GLYCOGENOLYSIS METABOLISM: Note #1. 3 of 3

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