Glycogen is the major storage form of glucose found mainly in the liver and skeletal muscles. It is formed from glucose through glycogenesis and broken down into glucose through glycogenolysis. These pathways are regulated by enzymes like glycogen synthase and glycogen phosphorylase in response to hormones like insulin and glucagon to maintain blood glucose levels. Deficiencies in enzymes of glycogen metabolism can result in glycogen storage diseases characterized by hypoglycemia, hepatomegaly and other symptoms.
Glycogenolysis, process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting. These slides will provide you detail explanation of Glycogenolysis.
Glycogenolysis, process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting. These slides will provide you detail explanation of Glycogenolysis.
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Glycogen is the storage from of glucose. The metabolism of glycogen both as glycogenolysis, breakdown of glycogen, and glycogenesis, formation of glycogen along with their regulation is briefed in the slides.
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Glycogen is the storage from of glucose. The metabolism of glycogen both as glycogenolysis, breakdown of glycogen, and glycogenesis, formation of glycogen along with their regulation is briefed in the slides.
Glycogen is the storage form of Glucose which maintain the blood glucose level under various condition. Glycogen Metabolism is the important pathway of carbohydrate metabolism which gives the information about the glycogen synthesis (Glycogenesis), Glycogen breakdown (Glucogenolysis). Glycogen metabolism also gives the information how this pathway is regulated. Their are various diseases which are associated with this metabolism, commonly known as Glycogen storage diseases.
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2. Energy Reserve
Major storage form of glucose
Stored mainly in the liver, skeletal muscles.
Insoluble – osmotically inactive.
High energy than same weight of glucose.
Readily mobilisable.
3.
4. O
O
CH2
O
O
HOCH2
O
O O
HOCH2
-1,4 linkage
between two
glucose units
-1,6 linkage
between two
glucose units
R
R
terminal ends
Glucose residue linked by -1,4
Glucose residue linked by -1,6
R Reducing end attached to glycogenin
5. stored mainly in the liver, skeletal muscles.
Stored in Cytoplasm as granules.
Glycogen in liver (6-8%) is higher than that in the
muscles (1-2%).
% of Tissue
Weight
Tissue Wt.
Body
Content
Liver glycogen 5.0 1.8 kg 90 g
Muscle glycogen 0.7 35 kg 245 g
Extracellular glucose 0.1 10 L 10 g
6. Controlled breakdown of glycogen releases glucose – serves
as a buffer to maintain blood-glucose levels.
Glucose is the only fuel used by the brain, except during
prolonged starvation.
Glucose from glycogen is readily mobilized and thus a good
source of energy for sudden, strenuous activity.
Unlike fatty acids, the released glucose can provide energy in
anaerobic condition.
About 5 hrs after taking food, the bl. glucose tends to
fall.
But, glycogen is lysed to glucose so that the energy needs
are met.
After about 18 hours fasting, most of the liver glycogen is
depleted, when depot fats are hydrolysed and energy
requirement is met by fatty acid oxidation.
7. Liver glycogen maintain blood glucose level particularly
between meals.
First line of defense against declining blood glucose levels
especially between meals.
Muscle glycogen is a readily available source of glucose in
the exercising muscles.
Deficient mobilization and abnormal accumulation of
glycogen leads to certain disorders called as GLYCOGEN
STORAGE DISEASES which can lead to muscular weakness
and even death in the affected individual.
8. Definition: It is the pathway for the formation of
glycogen from glucose
Substrate: Glucose
Site :Liver, Skeletal Muscles
Subcellular site: Cytosol.
Steps:
1. Activation of Glucose (Synthesis of UDP-
Glucose)
2. Initiation (Synthesis of Glycogen Primer)
3. Elongation of chain
4. Formation of branches in Glycogen
9. Synthesis of UDP-Glucose : Activated form of Glucose
Glucose
Glucose-6-phosphate
Glucokinase
Hexokinase
Glucose-1-phosphate
Phosphoglucomutas
e
ADP
UDP- Glucose
UDP-Glucose
pyrophosphorylase
ATP
UTP
PPi2Pi
ensures the
Irreversibility of this
reaction.
Pyrophosphatase
11. Primer is a preexisting (1→4) glucosyl chain which
will accept the
glucosyl residues donated by UDPG.
Normally a fragment of glycogen serves as a
primer.
When glycogen stores are depleted, a specific
protein known as
GLYCOGENIN provides the site at which the primer is
built.
Synthesis of Primer
to initiate Glycogen synthesis:
14. The branch points - created by the action of
Branching enzyme or glucosyl 4:6
transferase.
When the chain is minimum 11 glucose
residues long, branching enzyme removes a
block of 6-8 glucosyl units from the non
reducing end of the chain and attaches it via
an (1→6) linkage to a glucose residue of the
same or other chain.
16. Branching increases the solubility of glycogen.
Branching creates more glucose residues , thus
storage of glycogen as a compact molecule.
Branching creates a large number of
terminal residues, the sites of action of
glycogen phosphorylase and synthase .
Thus, branching increases the rate of glycogen
synthesis and degradation (rapid metabolism of
glycogen).
17. A small amount of glycogen is continuously
degraded in the lysosomes.
By the lysosomal enzyme α-1,4-glucosidase (acid
maltase).
The significance of this pathway is unknown.
However, a deficiency of this enzyme cause
accumulation of glycogen in the cytosol.
Results in glycogen storage disease type II
(Pompe’s disease)
18. Rate limiting enzyme - Glycogen Synthase.
Switch On- Glucose, Energy Is High.
Regulated By-
1.Allosteric regulation: Glucose-6-phosphate (+ve
modifiers)
in well-fed state.
2.Covalent modification : By phosphorylation &
dephosphorylation
Glycogen synthase-a
(Dephosphorylated)
Glycogen synthase-b
(Phosphorylated)
(active) (Inactive)Protein phosphatase
Protein Kinase
20. Definition: It is the degradation of glycogen to
glucose 6-phosphate & glucose in
muscle & liver respectively.
Substrate: Glycogen
Site: Liver, Skeletal Muscles
Subcellular site: Cytosol.
Steps: 1.Action of Glycogen Phosphorylase
2.Action of Debranching Enzyme
3.Formation of Glucose.
21. 1.The Key enzyme of glycogenolysis – Glycogen
Phosphorylase.
Phopshorolytic cleavage of α(1→4) glycosidic
bonds to form Limit Dextrin.
Glucose – 1-PGlycogen +Glycogen
( n residues) (n-1 residues)
Phosphorylase
+ Pi
22. Glucosyl 4:4 transferase activity transfers the 3 of
the 4 glucosyl units and involves cleaving of an
α(1→4)linkage at one site and formation of new
α(1→4)bond elsewhere.
The key enzyme for removing branch points is
the debranching enzyme - α (1→6) glucosidase –
breaks α (1→6) bonds - free glucose released.
Ratio of Glu-1-P to Free Glucose – 8:1.
24. The rate limiting enzyme of glycogenolysis is Glycogen
Phosphorylase which is regulated by-
1.Allosteric regulation –
AMP
ATP in liver and muscles
Glucose in liver
Glucose-6-phosphate in muscles
2.Covalent modification-Phosphorylated form is active.
3.Ca ions- activates phosphorylase kinase
Regulation of
Glycogenolysis:
(-ve modifiers)
(+ve modifiers)
(active)(inactive) Protein phosphatase
(phosphorylated)(dephosphorylated)
Glycogen phosphorylaseGlycogen phosphorylase
Phosphorylase kinase
26. Overall regulation
The Glycogen metabolism is mainly involved mainly in
regulation of Blood Glucose, these are tightly regulated.
Regulation Of Glycogen Metabolism Is Effected By A
Balance In Activities Between Glycogen Synthase &
Phosphorylase.
Inhibition Of Glycogenolysis Enhances Net Glycogenesis,
And Inhibition Of Glycogenesis Enhances Net
Glycogenolysis.
28. Metabolism
Functional role of glycogen differs from tissue to tissue…
In Liver-
Following the meal, excess of glucose is removed from
the circulation & stored as glycogen (Glycogenesis).
Between meals, blood glucose levels are maintained within
normal range by releasing glucose from glycogen
(Glycogenolysis).
In muscle-
Muscle glycogen acts as ready source of glucose for
glycolysis within muscle itself during muscle contraction.
Muscle cannot release glucose into the blood, because
of the absence of enzyme glucose 6 phosphatase. Thus
it cannot be used for blood glucose regulation.
29. Glycogen storage diseases or (Glycogenosis)
A group of inherited disorders,
rare , autosomal Recessive.
X- linked .
Deficiency of Enzymes of either glycogen
synthesis or glycogen break down.
Deposition of normal or Abnormal Glycogen in
tissues.
Disorders of Glycogen metabolism
30. Types- Hepatic (I, III, IV ,VI and VIII)
Myopathic (V and VII)
General features –
Hypoglycemia,
hepatomegaly (due to accumulation of glycogen in liver).
lactic acidosis.
Muscle weakness,
cramps, pain ,
easy fatigue in myopathic forms.
Hepatic fibrosis.
poor exercise tolerance.
33. Symptoms :
• Enlarged Liver And Kidneys
• Low Blood Sugar
• High Levels Of Lactate, Fats, And
Uric Acid In The Blood
• Impaired Growth And Delayed
Puberty
• Bone Thinning From Osteoporosis
• Increased Mouth Ulcers And
Infection
34. Type I (VonGierke's disease)
Glucose
Severe
hypoglycemia
between meals
Glucose 6-phosphatase
Glucose 1-P
UDP glucose
Glycogen
Liver glycogen is normal
structure but present in large
amounts.
HEPATOMEGALY
Fructose 1,6- P 6 phosphogluconate
Uric acid
Ribose 5- PPyruvate ↑Lactate
Acetyl CoA
Fatty acids
Ketone bodies
Cholesterol Increase lipolysis
in adipose tissue
Glucose 6- Phoshate
Hyperlipidemia
Hyperuricemia
35. Diagnosis - by Liver Biopsy .
Treatment – by frequent meals , nasogastric
feeding at night to maintain blood glucose
concentration.
36. 39 of 44
Ashok KattaGlycogen Metabolism
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Ashok Katta
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Dept. Of Biochemistry
Dhanalakshmi Srinivasan Medical
College, Siruvachur,
Perambalur - 621212