Transcript Document

Glycogen metabolism
· It is the storage from of glucose in animals
· Stored in liver (6-8%) and muscle (1-2%)
Helps to maintain the blood glucose levels,between
meals
Glycogen stores increase in a well-fed state depleted
during fasting
· Muscle glycogen serves as a fuel reserve for the
supply of ATP during muscle contraction
In homopolysaccharide, glucose molecules held
together by - 1,4 linkages. Branch with -1, 6 linkage.
Glucokinase in liver and hexokinase in muscle which
converts glucose to glucose–6 phosphate
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Glycogenesis
Synthesis of glycogen from glucose
Occurs in liver and muscle
Storage from in liver and muscle
After the meal excess glucose is converted into
glycogen
UDPG is the carrier of glucose
Glucose from UDPG is attached at the non-reducing
end of glucose molecules of glycogen primer
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ATP ADP
Glucose
Phosphoglucomutase
Glu –6-P
Glu-1-P
Hexokinase
Glucokinase
UDPG pyrophosphorylase
UTP
PPi
Uridine diphosphate glucose (UDPG)
Glycogen synthase
Glycogen primer
UDP
Glycogen
(1, 4 glucosyl units) n
(1, 4 and 1,6
Branching enzyme
Glucosyl units) n (Amylo-1, 4-1,6- transglucosidase)
(Glucosyl -4,6 transferase)
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Glycogenesis
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
It is found that in the absence of glycogen primer,
a specific protein,GLYCOGENIN can accept glucose
from UDPG. The initial glucose is attached to the
OH group of tyrosine residue of glycogenin.
The enzyme glycogen initiator synthase
transfers the first molecule of glucose to glycogenin.
Later glycogenin itself takes up a few glucose
residues to form a fragment of primer
 Branching enzyme (Amylo 1,4 –1,6 transglucosidase
transfers 6 glucose residues portion from one chain
to a neighbouring chain to form a -1,6 – linkage
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Glycogenolysis
Breakdown of glycogen to glucose
·Occurs in liver and muscle
·End product of liver glycogenolysis is glucose
·Muscle glycogenolysis is lactate (strenuous exercise)
Muscle and brain does not contain glu-6-phosphatase
Phosphorylase
Glycogen
Pi
Glu-1-P
Phosphoglucomutase
Glu –6-P
Glu-6-Phosphatase
H2O
Pi
Glucose
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 Phosphorylase phosphorolytically splits -1,4
glucoside bonds from the outermost chains of
glycogen until 4 residues remain on either side of
– 1.6 branch point [limit dextrin]
  1.4 glucan transferase transfers 3 glucose
residue portion from one side chain to the other
exposing -1,6 branch points
 Amylo 1, 6 glucosidase splits the 1,6 linkages
 Acid maltase or -1,4-glucosidase (lysosomal enzyme)
degrades small quantity of glycogen. The significance of this
pathway is not clear
v
Muscle glycogenolysis
Glycogen  Glu-1-P  Glu-6-P   glycolysis  lactate
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Glycogenolysis
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Regulation of glycogenesis and glycogenolysis
· The glycogen synthase and phosphorylase exist in
active and inactive forms
· The dephosphorylated form of glycogen synthase is
active
· Phosphorylated form of phosphorylase is active
The activation of phosphorylase depends on high
cAMP level. At the same time high cAMP level
inactivates glycogen synthase
Glycogen synthase b
Phosphorylase a
H2O
Protein phosphatase
Pi
Glycogen synthase a
Phosphorylase b
(Glycogenesis ON)
(Glycogenolysis OFF)
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·
·
Allosteric regulation
In a well fed state Glu–6– P level is high which
activates glycogen synthase
On the other hand glu-6-p and ATP allosterically
inhibit phosphorylase
Free glucose also act as inhibitor to phosphorylase
Glucose –6 –P ATP Liver glucose Muscle AMP
_
_
_
Glycogen Phosphorylase +
Ca2+
Glycogen
Glu-1-Phosphate
Glycogen Synthase
+
Glucose-6-phosphate
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Adrenaline (Liver and muscle)
Glucagon + (Liver only)
Adenylate Cyclase
Adenylate Cyclase
ATP
cAMP
PPi
Protein Kinase
Protein Kinase
ATP ADP
ATP ADP
Phosphorylase
Phosphorylase Glycogen
Glycogen
Kinase
kinase
Synthase (a)
synthase (b)
Phosphorylase (b)
Phosphorylase (a)
2ATP
2ADP
Glycogen
Glucose-1-P
Pi
cAMP
51 AMP
+ Phosphodiesterase
Insulin
Glycogenesis ON
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GLYCOGEN STORAGE DISEASES
Genetic diseases [may be inherited]
Deposition of abnormal type or quantity of glycogen in the tissues
Diseases
Defect and Features
Type I.
Glucose – 6 – phosphatase [liver]
Von Gierke’s disease
Accumulation of glycogen in liver
Hypoglycaemia and ketosis
Type II.
Lysosomal -1, 4 – glucosidase
Pompe’s disease
Glycogen accumulates in
lysosomes, in all tissues
Enlarged liver and heart
Type III.
Debranching enzyme [amylo -1,6Limit dextrinosis
glucosidase
[Coris disease]
Accumulation of polysaccharide
[limit dextrin] liver, heart, & muscle
TypeIV. Amylo pectinosis or Branching enzyme (glucosyl 4-6 transferase)
Andersons disease
Accumulation of polysaccharide with few
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branch
points. Cirrhosis of liver
Muscle glycogen phosphorylase
Glycogen accumulates in the muscle
Diminished tolerance to exercise
Type VI.
Liver glycogen Phosphorylase
Hers disease
Liver enlarged
Von Gierke’s Disease
1. Fasting hypoglycemia
2. Lactic acidemia:Glucose is not synthesized from lactate produced in
muscle and liver. Lactate level increases and pH decreases
3. Hyperlipidemia: Block in gluconeogenesis leads to mobilisation fat to
meet energy requirement. So This increases free plasma FA & ketone
bodies.
4. Hyperuricemia: Accumulated glucose -6-p diverted to HMP pathway,
leading to increased synthesis of ribose and nucleotides, this enhances
metabolism of purine nucleotides and to uric acid later
5. Massive liver enlargement leads to cirrhosis
6. Children fail to grow
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Given small quantity of food atDRfrequent
intervals
Type V
McArdles disease
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