Na

1. • It’s a storage form of glucose
• It’s a 1,4-glycosidic large branched polymer of
glucose residues
• Most of the glucose residues are linked by
-bondsα
• Branches at about every tenth residue are
created by α-1,6-glycosidic bonds.
• α-glycosidic linkages form open helical polymers,
whereas β linkages produce nearly straight
strands
Glycogen metabolism

3. Why store glucose as glycogen?
• Serves as a buffer to maintain blood-glucose
levels between meals
• the glucose from glycogen is readily mobilized
and is therefore a good source of energy for
sudden, strenuous activity
• Unlike fatty acids, the released glucose can
provide energy in the absence of oxygen and
can thus supply energy for anaerobic activity

4. • Glycogen is stored in the liver and muscle
• Large amounts in the liver(10%) compared to
the muscle stores(2%)
• Glycogen is present in the cytosol in form of
granules varying in diameter
• Break down in the liver is regulated to
maintain glucose needs of the whole organism
while that in the muscle meets energy
requirements of the muscle itself

5. • Glycolysis degradation consists of three steps
– the release of glucose 1-phosphate from glycogen
– the remodeling of the glycogen substrate to
permit further degradation
– the conversion of glucose 1-phosphate into
glucose 6-phosphate for further metabolism

6. • The glucose 6-phosphate derived from the
breakdown of glycogen has three fates
• It is the initial substrate for glycolysis
• it can be processed by the pentose phosphate
pathway to yield NADPH and ribose derivatives
• it can be converted into free glucose for release
into the bloodstream. This conversion takes place
mainly in the liver and to a lesser extent in the
intestines and kidneys.

7. • Phosphorylase Catalyzes the Phosphorolytic
Cleavage of Glycogen to Release Glucose 1-
phosphate
• Glycogen phosphorylase is the key enzyme in
glycogen breakdown
– cleaves its substrate by the addition of
orthophosphate (Pi) to yield glucose 1-phosphate
– The cleavage of a bond by the addition of
orthophosphate is referred to as phosphorolysis

8. • Phosphorylase catalyzes the sequential removal
of glycosyl residues from the nonreducing ends of
the glycogen molecule (the ends with a free 4-OH
groups)
• Orthophosphate splits the glycosidic linkage
between C-1 of the terminal residue and C-4 of
the adjacent one
• it cleaves the bond between the C-1 carbon atom
and the glycosidic oxygen atom, and the a
configuration at C-1 is retained

9. • Glucose 1-phosphate released from glycogen can be
readily converted into glucose 6-phosphate an
important metabolic intermediate, by the enzyme
phosphoglucomutase
• phosphorolysis proceeds far in the direction of glycogen
breakdown in vivo because the [Pi]/[glucose 1-
phosphate] ratio is usually greater than 100,
substantially favoring phosphorolysis
• The phosphorolytic cleavage of glycogen is energetically
advantageous because the released sugar is already
phosphorylated. In contrast, a hydrolytic cleavage would
yield glucose, which would then have to be
phosphorylated at the expense of the hydrolysis of a
molecule of ATP to enter the glycolytic pathway.
• An additional advantage of phosphorolytic cleavage for
muscle cells is that glucose 1-phosphate, negatively
charged under physiological conditions, cannot diffuse
out of the cell

10. Debranching enzyme
• The a-1,6-glycosidic bonds at the branch points
are not susceptible to cleavage by phosphorylase
• phosphorylase stops cleaving a-1,4 linkages when
it reaches a terminal residue four residues away
from a branch point
• Because about 1 in 10 residues is branched,
glycogen degradation by the phosphorylase alone
would come to a halt after the release of six
glucose molecules per branch.

11. • Two additional enzymes, a transferase and α-1,6-
glucosidase, remodel the glycogen for continued
degradation by the phosphorylase
• The transferase shifts a block of three glycosyl
residues from one outer branch to the other
• This transfer exposes a single glucose residue
joined by an a-1,6-glycosidic linkage. a-1,6-
Glucosidase, also known as the debranching
enzyme, hydrolyzes the a-1, 6-glycosidic bond,
resulting in the release of a free glucose
molecule.

12. Conversion of Glucose 1-phosphate
into Glucose 6-phosphate
• Glucose 1-phosphate formed in the
phosphorolytic cleavage of glycogen must be
converted into glucose 6-phosphate to enter
the metabolic mainstream.
• This is done by phosphoglucomutase

13. Glucose 6-phosphatase
• the phosphorylated glucose produced by
glycogen breakdown, in contrast with glucose,
is not readily transported out of cells
• Glucose 6-phosphatase found in the liver
cleaves the phosphoryl group to form free
glucose and orthophosphate
• This reaction occurs in the lumen of the
endoplasmic reticulum

14. • Glucose 6-phosphatase is absent from most
other tissues because glucose 6-phosphate is
retained for the generation of ATP