Last edited: 1/24/2022

GLYCOGENESIS
Glycogenesis: Glycogen and Reactions of Glycogenesis Medical Editor: Jona Frondoso

OUTLINE I) INTRODUCTION

I) INTRODUCTION ........................................................... 1 (1) Two main organs of glycogenesis

II) GLYCOGEN ................................................................. 1
Liver – Maximum glycogen storage capacity of 100g
(A) GLUCOSE ................................................................................. 1
(B) GLYCOSIDIC BOND ..................................................................... 1 Muscle – Maximum glycogen storage capacity of 300-400g
(C) GLYCOGEN ............................................................................ 1 (2) Glycogenesis occurs during Fed state
III) REACTIONS OF GLYCOGENESIS ........................... 2 ↑ Blood glucose levels (hyperglycemia)
(A) STEP 1: PHOSPHORYLATION OF GLUCOSE ............................. 2 o Not pathological
(B) STEP 2: ISOMERIZATION OF G6P TO G1P ............................... 2
o Still within normal glucose levels (80-120 mg/dL)
(C) STEP 3: ACTIVATION OF G1P .................................................. 2
(D) STEP 4: GLYCOGEN SYNTHESIS .............................................. 3 Enough to trigger the production of insulin
o Insulin – hormone produced by pancreatic beta cells
IV) APPENDIX .................................................................. 4
V) REVIEW QUESTIONS................................................. 4
VI) )REFERENCES .......................................................... 4

II) GLYCOGEN
(A) GLUCOSE (B) GLYCOSIDIC BOND
6-carbon molecule A bond is formed between C1 of one glucose and C4 of
Usually cyclic another glucose
o Water (H2O) is lost in the bond formation process
Must Know: Formed via a hemiacetal-alcohol reaction
General Structure of Glucose (Figure 1)
(1) 2 types of glycosidic bond (Figure 2)
Very important to remember is the number of carbons.
Carbons are numbered from 1 to 6 (i) α – glycosidic bond
Carbon 1 (C1) = carbonyl (-COOH) C = reducing end
If the bond formed is between a C1 and C4 which
Carbon 4 (C4) = non-reducing end
hydroxyl groups are both pointing upwards
Throughout the lecture notes, glucose will be represented
by a circle for simplicity. (ii) β – glycosidic bond
If the bond formed is between a C1 and a C4 which
hydroxyl groups are pointing in opposite directions.

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

Figure 2. Alpha and beta glycosidic bonds. [Association of the British

Pharmaceutical Industry, 2014]

(C) GLYCOGEN
Branched glucose polysaccharide composed of chains of
glucose units linked by α-1,4 bonds with α-1,6 branches
every 8-10 residues

GLYCOGENESIS METABOLISM: Note #1. 1 of 4

 III) REACTIONS OF GLYCOGENESIS
Location: cytosol [Harvey & Ferrier, 2011]

(A) STEP 1: PHOSPHORYLATION OF GLUCOSE (B) STEP 2: ISOMERIZATION OF G6P TO G1P

Glucose is brought into the cell via GLUT-2 transproter Reversible conversion of glucose-6-phsophate to the
(GLUT transporter in the liver) (Figure 3) isomer glucose-1-phosphate (Figure 4)
Addition of phosphate group from ATP to glucose Phosphoglucomutase catalyzes the shift of phsophate
producing glucose-6-phosphate (G6P) and ADP group from C6 to C1
Catalyzed by glucokinase
o Glucokinase (in liver)
o Hexokinase (in muscle)

Figure 3. Transport of glucose into the cell and its

phosphorylation to G6P.

Figure 4. Isomerization of G6P to G1P.

(C) STEP 3: ACTIVATION OF G1P

Glucose-1-phosphate is activated before addition to glycogen chain (Figure 5)
Energy is released when pyrophosphorylase catalyzes the reaction [Nelson & Cox, 2005]
High-energy compound uridine triphosphate (UTP) transfers UMP to G1P to give UDP-glucose and pyrophosphate (PPi)
o UTP – Nucleotide composed of uracil, ribose, and 3 phosphate groups
o UDP-glucose - Basic unit to make glycogen
Pyrophosphatase catalyzes the exergonic breakdown of PPi (-∆G)
o Energy released is used in the glycogen synthesis, an endergonic process (+∆G)

Figure 5. Activation of G1P by formation of UDP-glucose.

2 of 4 METABOLISM: Note #1. GLYCOGENESIS

 (D) STEP 4: GLYCOGEN SYNTHESIS
Glycogenin (2) Chain Extending Activity
Base molecule used to build glycogen (homodimer protein) Glycogen synthase catalyzes the transfer of glucose
Already present in the liver or muscle cell residue from UDP-glucose to the non-reducing end of an
Has tyrosine coming off its surface (Figure 6) initially added glucose molecule (Figure 8)
o Tyrosine – amino acid containing hydroxyl group Glucose units are connected to each other by α-1,4
glycosidic bond.

Figure 6. Hydroxyl group of the tyrosine of glycogenin.

(1) Autoglycosylation
Reaction is catalyzed by glycogenin itself
C1 of an initial glucose unit, in the form of UDP-glucose, is
attached to the hydroxyl group of a specific tyrosine in
glycogenin
o In the process, the bond between UDP and glucose of
UDP-glucose is broken.
o UDP can combine to an inorganic phosphate to
regenerate UTP
Autoglycosylation stops once a third glucose unit has been
added Figure 8. Chain extending activity of glycogen synthase.
Bond formed between glycogenin and an initial glucose (3) Branching
unit is NOT a glycosidic bond
Glycogen branching enzyme has a glucosyltransferase
activity, it cuts the bond and transfers 5 glucose residues
from non-reducing end of a glycogen having at least 10
residues to OH group of C6 of interior glucose of the same
branch to form a new branch (Figure 9)
Has α-1,4 glucosidase activity and α-1,6 glycosidic
bond activity

Figure 9. Alpha-1,4 glucosidase activity and alpha-1,6

glycosidic bond activity of glycogen branching enzyme.

Figure 7. Autoglycosylation of glycogenin.

GLYCOGENESIS METABOLISM: Note #1. 3 of 4

 IV) APPENDIX

Table 1. Summary of the Reactions in Glycogenesis and the Enzymes Catalyzing Them
Reaction Enzyme
1. Phosphorylation of glucose Glucokinase (if liver) ; Hexokinase (if muscle)
2. Isomerization of G6P to G1P Phosphoglucomutase
3. Activation of G1P Pyrophosphorylase
4. Autoglycosylation Glycogenin
5. Glycogen chain elongation Glycogen synthase
Glycogen branching enzyme (with α-1,4 glucosidase activity and α-1,6 glycosidic
6. Branching
bond activity)

V) REVIEW QUESTIONS
Which of the following is correct about
glycogenesis?
a. It occurs in the mitochondria.
b. Maximum glycogen storage of the liver is 100g.
c. Fasting state favors glycogenesis.
d. Insulin does not favor glycogenesis.

Glucose residues are added to the glycogen chain as:

a. UTP-glucose
b. UDP-glucose
c. Glucogenin
d. Glucose-1-phosphate

Arrange the following statements sequentially:

1. Activation of G1P
2. Autoglycosylation
3. Glycogen chain elongation
4. Phosphorylation of glucose
5. Isomerization of G6P to G1P
6. Branching

a. 4-5-1-2-3-6
b. 4-5-1-3-2-6
c. 2-4-5-1-3-6
d. 2-4-5-1-6-3

Which of the following statements about

autoglycosylation is correct?
a. Bond between UDP and glucose is formed.
b. C1 of an initial glucose unit is attached to the hydroxyl
group of a specific serine in glycogenin
c. Bond formed between glycogenin and an initial
glucose unit is a glycosidic bond
d. Reaction is catalyzed by glucogenin itself.

Which of the following statements glycogen

branching enzyme is correct?
a. It has a α-1,4 glucosidase activity.
b. It has a α-1,6 glycosidic bond activity.
c. It transfers glucose residues to an OH group.
d. All of the statements are correct.

VI) )REFERENCES

Association of the British Pharmaceutical Industry. (2014).

Carbohydrates: monosaccharides, disaccharides, and
oligosaccharides. Retrieved from ABPI:
https://www.abpischools.org.uk/topic/chemistryoflife/5
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.

4 of 4 METABOLISM: Note #1. GLYCOGENESIS