GLYCOGENOSIS AND

GLYCOGENOLYSIS

SUBMITTED TO:
SIR IJAZ AHMED.
SUBMITTED BY:
MUHAMMAD
SHAHID NAZIR.
ROLL NUMBER:
Bsmls f-19-027
WHAT IS GLYCOGEN?
 Glucogen is a very large branched polymer of
glucose residue. Mr about 107 Dalton (up to 120,000
glucose residuesglucose units).
 Glycogen is present in the cytosol of animal cells in
the form of granules ranging in diameter from 10 to
40 nm.
 The two major sites of glycogen storage are the liver
and skeletal muscle.
 The core of the glycogen particle is a protein
 The polymer is composed of units of glucose linked
(glycogenin,
alpha(1-4) G).branches occurring alpha(1-
with
6)approximately every 8-12 residues
DEFINITION OF GLYCOGENESIS:
• It is the formation of glycogen, which occurs in all
tissues of the body, but in large amount in liver and
muscles.
• There are very small amount of glycogen synthesis
and storage in the central nervous system, this is why
it is completely dependent on blood glucose as a
source of energy.
• Site: Cytosol of all cells particularly liver and
The Sugar Nucleotide UDP-
muscles. Glucose Donates Glucose
for Glycogen Synthesis
 GLYCOGEN SYNTHESIS
 A distinct system of enzymes exists for endergonic
glycogen synthesis, coupled ultimately to the
hydrolysis of ATP.
 Glucose 6-phosphate isomerizes to glucose 1-
phosphate by the action of phosphoglucomutase.
 Synthesis of an activated form of glucose (UDP-
glucose) :from glucose 1-phosphate and UTP (uridine
triphosphate) in a reaction catalyzed by UDP-glucose
pyrophosphorylase
UDP-glucose
pyrophosphorylase

This reaction is reversible, but it is driven by the essentially

irreversible and rapid hydrolysis of diphosphate catalysed by
inorganic pyrophosphatase
PPi + H2O = 2Pi
ELONGATION OF
GLYCOGEN CHAIN
Glycogen synthase – the key
regulatory enzyme in glycogenesis
catalyses formation of an α-1,4-glycosidic
bonds by the transfer of glucosyl from
activated UDP-glucose to an existing chain
(a primer)
GLYCOGEN PRIMER
Glycogen synthesis needs a basic
molecule on which the glucose residues
can be added so that the chain can get
elongated. Glycogen fragments which
already exist can act as this primer. In
glycogen depleted condition, a protein
primer called glycogenin acts as the
flooring to which the glucose molecules
from UDP glucose are added like bricks.
GLYCOGENESIS STEPS

glycogen synthase
links between the
1st C atom of the
standing glucose
residue on the end
point of the fragment
and 4th carbon of the
glucose residue that
is being added to the
fragment. This forms
the 1→ 4 glycogenic
link. The enzyme
catalysing this step is
Glycogen synthase
THE BRANCHING IN GLYCOGEN
 After around 8 residues, branching begins and the
branches provide more number of activated glucose
residual ends for the UDP glucose to get attached to.
 This branching is brought about by branching enzyme
called amylo-α(1→4) → α(1→6)-transglucosidase.
 forms α-1,6-linkages that make glycogen a branched
polymer.
 Branching is important because it increases the
solubility of glycogen and increases the velocity of
glycogen synthesis and breakdown (creating a large
number of non-reducing ends).
REGULATION OF
GLYCOGENESIS
 Glycogen synthesis is strictly monitored to regulate the
blood glucose level. It is activated in well fed state and
suppressed in fasting. According to basis of regulation of
metabolic process, the factors regulating Glycogenesis are:
1.AVAILABILITY OF SUBSTRATE
In well-fed state, when the blood glucose level is
high, glucose 6 phosphate the substrate for UDP
glucose is also high. This allosterically increases
Glycogenesis. Also during fasting, the substrate is
low and there is need for glucose which causes
2.HORMONE:
break down of glycogen which is opposite of
Glycogen synthase, the key enzyme of
Glycogenesis.
Glycogenesis exists in activate (dephosphorylated)
and inactive (phosphorylated) form. Hormones like
glucagon and epinephrine are diabetogenic i.e.
they increase the blood glucose level.
Thus they antagonize glycogen synthesis which is
an effective way of reducing blood glucose level and
storing it for further use.
These hormones succeeds in their function by series
of biochemical reactions which results in :
A. phosphorylation of glycogen synthase enzyme
rendering it inactive.
B. Insulin is an anti diabetic hormone. It lowers the
blood glucose level by stimulating the uptake of
glucose by muscle cells and Glycogenesis in liver
and muscle.
These phosphorylations are catalysed by the
action of protein kinases,
dephosphorylations by the action of
phosphoprotein phosphatases. The
phosphorylation of both key enzymes
depends primarily on the intracellular
GLYCOGEN DEGRADATION
GLYCOGEN DIGESTION IN THE
GASTROINTESTINAL TRACT
 is essentially the same as the digestion of amylopectin.
 Both saliva and pancreatic secretion contain α-
amylase, which catalyses hydrolytic splitting of α-
1,4-glucosidic bonds at random, unless they are near
chain ends or branch points.
 The products are then maltose, maltotriose and a
mixture of small branched fragments (with 5 - 9
glucose residues) called α-dextrins.
 Those products are hydrolysed to free glucose by
the action of both maltase and saccharase-
isomaltase, found in the plasma membrane of
mucosal cells of the duodenum and jejunum.
GLYCOGENOLYSIS
DEFINATION OF GLYCOGENOLYSIS
Glycogenolysis is the breakdown of the molecule
glycogen into glucose,a simple sugar that body
uses to produce energy.glycogen is essentially
stored energy in the form of long chain of
glucose.
Site:glycogenolysis takes place in muscles and
liver cells when more energy needs to be
produce.
BREAKDOWN OF GLYCOGEN (GLYCOGENOLYSIS):
INVOLVES
A.release of glucose-1-phosphate (G1P)
B.rearranging the remaining glycogen (as necessary) to
permit continued breakdown
C. conversion of G1P to G6P for further metabolism.
 G6P can be:
1. broken down in glycolysis
2. converted to glucose by gluconeogenesis
 GLYCOGENOLYSIS: Glycogen
breakdown in cells
- It occurs in Cytosol of all cells but high activity in liver and
muscles.
-Glycogenolysis requires the cooperation of two enzymes –
glycogen phosphorylase and – a debranching enzyme.
Glycogen phosphorylase- the key regulatory
enzyme in glycogenolysis
-catalyses the sequential phosphorolysis (not hydrolytic splitting)
of α-1,4-glycosidic bonds of glycosyl residues from the non-
reducing ends, and these only if they are more distant than four
residues from abranch point. So its action ends with a
production of several molecules of glucose 1-P and a limit dextrin

A limit
dextrin
GLYCOGEN DEBRANCHING ENZYME exhibits
two catalytic activities, it is a bifunctional enzyme:
1. The transferase activity shifts a block of three glucosyl
residues from one outer branch to the other.
2. α-1,6-glucosidase activity : convert alpha(1-6) branches to
alpha(1-4); causes hydrolysis of the α-1,6-glycosidic bond
resulting in the release of a free glucose molecules
 The debranching enzyme converts the branched
structure of a limit dextrin into a linear one:

 Phosphorylase can now attack the remaining α-1,4-

linked chain
 Phosphoglucomutase converts
glucose 1-phosphate into glucose 6-
phosphate, the intermediate of
glycolytic pathway
 phosphoglucomutase is needed to
form G1P for glycogen biosynthesis.
 The glucose-6-phosphatase (G6Pase)
catalyzes the last step of
gluconeogenesis - conversion of G6P
to glucose + phosphate. This enzyme
is necessary also for release of
glucose into the bloodstream from
glycogen metabolism (glycogen ->
G1P -> G6P -> Glucose).

It is interesting to note that G6 Phosphatase is ABSENT

FROM MUSCLE. This is because muscle does NOT export
glucose. the liver, on the other hand, DOES export
glucose and thus has abundant supplies of the enzyme.
so that when G6P is produced from glycogen breakdown,
it can enter glycolysis.
 CONTROL OF GLYCOGEN DEGRADATION
Epinephrine exerts it greatest effects on muscle and glucagon works
preferentially on the liver.
4 cAMP (increase is evoked by glucagon and/or adrenaline)

Protein
2 2,
kinase
A(C R Inactive) Protein kinase A (2 C,+ R2(cAMP)4
active)
2
ATP
Phosphorylase Phosphorylase kinase (-P2,
kinase active)
(inacti Ca2 4 4
+
ve) ATP ADP

2 Glycogen Glycogen a (inacti

phosphorylase b phosphorylase ve)
Activation of (dimeric, inactive) (tetrameric,
phosphorylase kinase by phosphorylated , active)
calcium is VERY important 4 4 Phosphorylase
in muscle for m contraction Pi
Protein
H2O
kinase is activated
phosphatase
by:
1. phosphorylation
2. Ca+2
3. Glucose is
negative effector
 Glycogen phosphorylase (GP) is regulated by
both allosteric factors and by covalent
modification. High energy substrates (ATP, G6P,
glucose) inhibit GP, while low energy substrates
(AMP, others) activate it.
 the liver GPb form of the enzyme is
insensitive to AMP, unlike the muscle GPb.
 Glucose binding to liver GPa causes it to
convert into the inactive form. This does not
happen in muscle
 Glycogen Storage Diseases
 Glycogen storage diseases are groups of
inherited disorders characterized by deposition
(over-storage) of an abnormal type or quantity
of glycogen or failure of storage of glycogen in
the tissues.
 They are mainly due to deficiency of one of
enzymes of glycogenesis or glycogenolysis,
phosphofructokinase, or lysosomal glycosidases.
 these include type I to type VIII glycogen
storage diseases.
Limit Dextrinosis

Tarui’s
disease
REFERENCES:
https://en.wikipedia.org
www.checkdiabetes.org
www.sciencedirect.com
www.researchgate.net
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