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Updated: 5/1/2020

Glycogen

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  • Overview
    • Structure
      • glycogen
        • polymer of glucose
          • straight chain with α-1,4-bond
          • branches with α-1,6-bond
      • glycogen granule
        • core
          • glycogenin
    • Function
      • energy reserves that can provide glucose during a fast or ↑ energy demand
        • supplies exhausted in < 24 hrs
      • stored mainly in the liver and muscle
        • muscle does not have glucose-6-phosphatase so it cannot release free glucose
          • stores for its own consumption
        • liver does have glucose-6-phosphatase so it can release free glucose
          • can use supplies to maintain blood glucose levels
  • Glycogenesis
    • Glycogen synthesis
    • Pathway
      • glucose-6-phosphate converted to glucose-1-phosphate
      • UDP group added to form UDP-glucose
      • UDP-glucose added to polymer in an α-1,4 linkage
        • catalyzed by glycogen synthase
          • rate limiting step of glycogen synthesis
      • polymer rearranged to create α-1,6 linked branches
        • catalyzed by branching enzyme
          • deficiency = Anderson disease
    • Regulation
      • glycogen synthase
        • in liver
          • activated by insulin
          • inhibited by glucagon, epinephrine
        • in muscle
          • activated by insulin
          • inhibited by epinephrine
  • Glycogenolysis
    • Glycogen catabolism
    • Pathway
      • glucose-glucose bond broken by addition of a phosphate
        • catalyzed by glycogen phosphorylase
          • rate limiting step of glycogenolysis
            • hepatic deficiency = Hers disease (type VI)
            • muscle deficiency = McArdle disease (type V)
      • glucose-1-phosphate freed
        • converted to glucose-6-phosphate
      • debranching enzymes removes α-1,6 linked branches
        • deficiency = Cori's disease (type III)
      • liver converts glucose-6-phosphate to glucose
        • catalyzed by glucose-6-phosphatase
          • deficiency = von Gierke disease (type I)
      • muscle puts glucose-6-phosphate into glycolysis
    • Regulation
      • glycogen phosphorylase
        • in liver
          • activated by epinephrine, glucagon
            • via cAMP/protein kinase A
          • inhibited by insulin
          • remember: exact opposite of glycogen synthase
            • hepatic glycogen regulatory processes both turn on forward direction and turn off reverse
        • in skeletal muscle
          • activated by epinephrine, AMP, Ca2+
          • inhibited by insulin, ATP
          • remember: since muscular glycogen can only supply itself, it is regulated by its own energy supply (AMP/ATP ratio); while liver must supply energy to many other tissues, it functions independently of AMP/ATP ratio in hepatocytes
  • Glycogen Storage Diseases (Glycogenolyses)
    • Overview
      • all disorders have abnormal glycogen metabolism
        • leads to an accumulation of glycogen within cells
        • organ dysfunction
      • remember: disorders numbered in order of pathway from end (glucose release) to beginning (breakdown of glycogen polymer)
    • Glucose release
      • Type I: von Gierke
        • lacks glucose-6-phosphatase
        • presentation
          • liver cannot release stored glucose
            • hepatomegaly
            • severe hypoglycemia
          • body must rely on fat/protein catabolism for energy
            • hyperlipidemia
            • hyperuricemia
            • lactic acidosis
          • normal glycogen structure
        • tests
          • stimulation test with glucagon, fructose, galactose
          • does not ↑ serum glucose
    • Lysosomal pathway
      • Type II: Pompe "trashes the Pump (heart)"
        • lacks lysosomal α1,4-glucosidase
          • degrades glycogen-resembling material in endosomes
        • presentation
          • buildup of glycogen in cardiac muscle
            • electron dense granules inside lysosomes
            • cardiomegaly
            • hypertrophic cardiomyopathy
    • Branching/debranching
      • Type III: Cori
        • lacks debranching enzyme
          • remember:
            • Cori = can't Catabolize branches
            • 6-pack core - alpha 1,6 glucosidase defective
        • presentation
          • liver cannot break down glycogen past a branch point
            • hepatomegaly
            • hypoglycemia
            • abnormal glycogen structure
              • short outer glycogen chains
      • Type IV: Anderson
        • lacks branching enzyme
          • remember: Anderson = can't Add branches
        • presentation
          • liver cannot form branched glycogen granules
            • hypotonia
            • cirrhosis
    • Phosphorylase
      • Type V: McArdles
        • lacks muscle phosphorylase
          • remember: McArdles = Muscle
          • can't breakdown glycogen to glucose-1-phosphate
          • accumulation of glycogen in muscle tissue
        • presentation
          • muscle weakness/cramps upon exertion
          • myoglobinuria
          • normal glycogen structure
      • Type VI: Hers
        • lacks hepatic phosphorylase
          • remember: Hers = Hepatic
        • presentation
          • hepatomegaly
          • fasting hypoglycemia
            • can be mild due to gluconeogenic compensation

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(M1.BC.15.74) You are presented with an infant boy who has repeatedly experienced hypoglycemia and seizures. On your exam, you note decreased muscle tone, growth retardation, and hepatomegaly. The patient has normal serum lactate. You review results of a liver biopsy, shown in Figure A. Further biochemical testing reveals abundant glycogen with abnormally short outer chains. Which of the following enzymes is most likely deficient in this patient?

QID: 106621
FIGURES:

Muscle glycogen phosphorylase

6%

(28/451)

Alpha-1,6-glucosidase

52%

(234/451)

Glucose-6-phosphatase

12%

(53/451)

Acid maltase

1%

(6/451)

Branching enzyme

27%

(121/451)

M 1 D

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(M1.BC.15.74) A 12-year-old male presents to the pediatrician after two days of tea-colored urine which appeared to coincide with the first day of junior high football. He explains that he refused to go back to practice because he was humiliated by the other players due to his quick and excessive fatigue after a set of drills accompanined by pain in his muscles. A blood test revealed elevated creatine kinase and myoglobulin levels. A muscle biopsy was performed revealing large glycogen deposits and an enzyme histochemistry showed a lack of myophosphorylase activity. Which of the following reactions is not occuring in this individuals?

QID: 106612

Converting glucose-6-phosphate to glucose

5%

(13/284)

Breaking down glycogen to glucose-1-phosphate

76%

(216/284)

Cleaving alpha-1,6 glycosidic bonds from glycogen

13%

(36/284)

Creating alpha-1,6 glycosidic bonds in glycogen

3%

(8/284)

Converting galactose to galactose-1-phosphate

0%

(1/284)

M 1 E

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Evidence (4)
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EXPERT COMMENTS (33)
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