BIOC 460 - DR. TISCHLER LECTURE 31

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BIOC 460 - DR. TISCHLER LECTURE 31
GLYCOGEN METABOLISM PATHWAYS/ALLOSTERIC CONTROL
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OBJECTIVES

• Glycogenolysis Pathway
• 1. general features describe glycogen
  phosphorylase.
• 2. different fates of glucose-6-P from
  glycogenolysis in liver vs muscle
• 3. Tense vs relaxed forms of glycogen
  phosphorylase activity
• 4. Function of phosphorylase kinase in promoting
  glycogen mobilization relative to the
  phosphorylation state of glycogen phosphorylase.
• 5. Explain the physiological basis for
• a) AMP activating and ATP inhibiting glycogen
  phosphorylase
• b) calcium activating phosphorylase kinase
• G-6-P inhibiting phosphorylase/activating
  glycogen synthase
• Why glycogen storage disease type I (von Gierke's
  disease) can lead to severe hypoglycemia but
  type V (McArdle's disease) does not cause
  hypoglycemia

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• Glycogenesis Pathway
• 1. general features describe glycogen synthase
• Carbohydrate loading
• Explain the physiological basis for G-6-P
  activating glycogen synthase
• 4. Compare two forms of glycogen synthase (d-form
  and i-form).

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Figure 1. The glycogen structure showing the
glycosidic bonds

• liver stores glycogen that provides 75 of
  glucose needed (mostly by RBC and brain) during
  first 24 hours of food deprivation
• muscle stores glycogen solely for its own
  needs lack of G-6-Pase prevents formation and
  secretion of glucose for use by other tissues
• highly branched structure to increase
  solubility provides many more sites for removal
  of glucose units that are phosphorylated by
  glycogen phosphorylase

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Glycogen
LIVER PATHWAY
Pi
glycogen phosphorylase
Glucose-1-phosphate
phosphoglucomutase
glucose-6-phosphatase
Glucose-6-phosphate
Glucose
Pi
glycolysis
X
(inhibited by lack of fructose-2,6-bisP)
Figure 2a. Glycogenolysis and the fate of
glycogen in liver and kidney
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Glycogen
MUSCLE PATHWAY
Pi
glycogen phosphorylase
Glucose-1-phosphate
phosphoglucomutase
Glucose-6-phosphate
glycolysis
Pyruvate
Figure 2b. Glycogenolysis and the fate of
glycogen in muscle.
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Glucose
Figure 3. Pathway of glycogen synthesis
(glycogenesis)
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activation by calcium inhibition by glucose-6-P
G-6-P ATP (in muscle)
Figure 4. Regulation of glycogen phosphorylase
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(No Transcript)
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Figure 6. Regulation of glycogen synthase
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GLYCOGEN STORAGE DISEASES
Disease Type Enzyme Deficiency Organ Location
von Gierke disease I glucose-6-phosphatase liver
McArdle disease V glycogen phosphorylase muscle
Type I Von Gierke Disease Hypoglycemia due to
defect of the final step of gluconeogenesis Decre
ased mobilization of glycogen produces
hepatomegaly.
Type V McArdle Disease Skeletal muscle
affected, but liver enzyme is normal No
hypoglycemia - muscle glycogen does not produce
glucose Temporary weakness and cramping of muscle
after exercise No rise in blood lactate during
strenuous exercise Muscle contains a high level
of glycogen