Glycogen

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Glycogen
2
Glycogen

• Liver
• 4 72 g
• Muscle
• 1 245 g
• Extracellular glucose
• 0,1 10 g
• Adult - man 70 kg
• His liver 1,8 kg
• His muscle mass 35 kg
• Blood volume 10 l

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Glycogen

• Muscle
• Glucose substrate for muscle glycolysis
• Liver
• Glucose store,
• Export of hexose
• Blood sugar
• Glycogenosis
• Deff. Of enzymes
• Muscle weakness N

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Glycogen level of liver
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• As a meal containing carbohydrates is eaten and
  digested,
• blood glucose levels rise
• pancreas secretes insulin.
• Glucose from the portal vein enters the liver
  cells (hepatocytes).
• Insulin acts on the hepatocytes to stimulate the
  action of several enzymes, including glycogen
  synthase.
• Glucose molecules are added to the chains of
  glycogen as long as both insulin and glucose
  remain plentiful. In this postprandial or "fed"
  state, the liver takes in more glucose from the
  blood than it releases.
• .

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• After a meal has been digested and glucose levels
  begin to fall, insulin secretion is reduced, and
  glycogen synthesis stops.
• About four hours after glycogen begins to be
  broken down and converted again to glucose.

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Glycogen metabolism
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Glycogen synthesis

• Muscle
• Hexokinase
• Liver
• Glucokinase
• Phosphoglucomutase
• Glucose-1,6-P cofactor
• Glycogen
• Primer glycogenin
• 37 kDa glycosilated Tyr

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Synthesis of glycogen
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Synthesis of glycogen
glikogenin
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Synthesis of glycogen
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Glycogenolysis
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Glycogen
P
P
P
Glygenolysis
Glycogenesis
Glucose-1-P
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Effect of epinephrin
X
Stimulus
R
cAMP
40X
ATP
Cent. Nervous syst.
Inakt. Protein Kinase A
Aktive Protein Kinase A
10X
Adrenal cortex
Phosphorylase Kinaseb
Phosphorylase Kinase a
100X
Glykogen phosphorylaseb
Glykogen phosphorylasea
1000X
Epinephrin
X
Glykogen
Glukose 1 P
10000X
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GDP
b
a
g
ATP
GTP
cAMP
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GTP
GDP
GDP
GTP
b
a
g
Gsa
g
b
g
P
GDP
Gsa
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4 cAMP
R
R
R
R
C
C
C
C
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• Protein Kinase Reactions
• Serine-Threonine Kinase / cAMP depentent Protein
  Kinase

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Tein, koffein
cAMP
AMP
PKA
PKA
Phosphorylase-kinase b
Phosphorylase-kinase a
Ca2
Phosphorylase a
Phosphorylase b
AMP
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Glycogen
P
P
P
Glycogenolysis
Glycogenesis
Glucose-1-P
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GLYCOGEN SYNTHASE ALSO IS PHOSPHORYLATED
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Glycogen synthase

• Glycogen synthasea dephosphorylated
• Glycogen synthaseb phosphorylated
• 4 identical subunit
• 7 Ser-OH residues/subunit

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Glycogen synthase

• 6 different protein kinases
• Phophorylase kinase (Ca2/Calmodulin dep)
• Ca2/Calmodulin dep.
• GSK-3
• GSK-4
• GSK-5
• Glucose-6-P allosteric activator of
  Glycogene-synthase kinaseb
• Insulin/muscle
• dephosphorylation / activation of
  Glycogen-synthaseb

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Protein Kinase Glycogen Synthase Phosphorylation Site
Phos b Kinase II
A-Kinase IA, IB, II, and IV
Ca/Calmodulin - Dependent Protein Kinase IB, II
Glycogen Synthase Kinase 3 IIIA, IIIB, IIIC
Glycogen Synthase Kinase 4 II
Casein Kinase I Nearly all sites
Casein Kinase II V
Protein Kinase C IA
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Name Type Enzyme Deficiency Tissues Chiefly Affected Clinical Consequences
Von Gierke's Disease I Glucose 6-phosphatase Liver, kidney Severly enlarged liver, severe hypoglycemia, lactic acidosis, ketosis, hyperuricemia, hyperlipemia
Pompe's Disease II 1,4-D-Glucosidase (lysosomal) Liver, heart, muscle Cardiac failure in infancy
Cori's Disease III Amylo-1,6-glucosidase ("Debranching" enzyme) Liver, muscle Similar to Type I, but milder
Andersen's Disease IV "Branching" enzyme Liver Liver cirrhosis, death usually before 24 months
McArdle's Disease V Phosphorylase Muscle Muscle cramps, easily fatigued
Hers' Disease VI Phosphorylase Liver Similar to Type I, but milder
Tarui's Disease VII Phosphofructokinase Muscle Similar to Type V
  VIII Phosphorylase kinase Liver Enlarged liver, hypoglycemia
  IX Glycogen synthase Liver  
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Von Gierkes Disease
Glucose 6-phosphatase liver and kidney
Here is another liver with a pale, bulging
surface. This time the liver is filled with
glycogen in von Gierke's disease, the glycogen
storage disease of children. Severly enlarged
liver, severe hypoglycemia, lactic acidosis,
ketosis, hyperuricemia, hyperlipemia
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POMPE'S DISEASE
When mannose 6-phosphate tags are added to acid
maltase enzyme molecules, the molecules stick
to receptors (docking sites) on the muscle
cells and are carried deeper inside the cells,
where they're needed.
Without mannose 6-phosphate tags, acid
maltase (1,4-D-Glucosidase) enzyme molecules
can't enter muscle cells from the bloodstream.
ENZYME TREATMENT BENEFITS BABIES WITH POMPE'S
DISEASE Babies with a metabolic muscle disorder
known as Pompe's disease, or acid maltase
deficiency, usually don't survive infancy because
they lack a vital enzyme that normally breaks
down glycogen in the heart and skeletal muscle
cells. Cardiac failure in infancy liver,
heart, muscle
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Forbes disease, Type III glycogenosis

• also called Cori's disease , or glycogenosis type
  III  rare hereditary disease in which the the
  metabolic breakdown of glycogen to the simple
  sugar glucose is incomplete, allowing
  intermediate compounds to accumulate in the cells
  of the liver. Affected persons lack the enzyme
  amylo-1,6-glucosidase, one of several enzymes
  involved in glycogen breakdown. Children with the
  disease have enlarged livers (which usually

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Andersens disease

• also called Glycogenosis Type Iv,   extremely
  rare hereditary metabolic disorder produced by
  absence of the enzyme amylo-14,16-transglucosida
  se (branching enzyme), which is an essential
  mediator of the synthesis of glycogen. An
  abnormal form of glycogen, amylopectin, is
  produced and accumulates in body tissues,
  particularly in the liver and heart. Affected
  children appear normal at birth but fail to
  thrive and later lose
• Liver cirrhosis, death usually before 24 months

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McArdle's Disease
Phosphorylase stain Absent Muscle fibers stain
yellowMyophosphorylase deficiency McArdle's
disease
Phosphorylase stain Normal more darkly than type
I
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