Glycogen B&B Flashcards

1
Q

what 3 enzymes are required to divert glucose-6-phosphate into synthesis of branched glycogen?

A
  1. UDP-glucose pyrophosphorylase
  2. glycogen synthase (alpha1,4 linkages)
  3. branching enzyme (alpha1,6 linkages)
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2
Q

what 3 enzymes are required for glycogen breakdown?

A
  1. glycogen phosphorylase (alpha1,4 linkages)
  2. debranching enzyme (alpha1,6 linkages)
  3. alpha1,4 glucosidase (lysosomes)
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3
Q

how does phosphorylation control the activity of glycogen synthase vs glycogen phosphorylase?

A

glycogen synthase is INACTIVATED by phosphorylation

glycogen phosphorylase is ACTIVATED by phosphorylation

this make sense, because recall glucagon/epinephrine phosphorylate things (via AC->cAMP->PKA) and want to promote glycogen breakdown to glucose

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4
Q

during periods of muscle contraction, glycogen phosphorylase can be phosphorylated/activated in the absence of hormones (glucagon, epinephrine) by ______

A

calcium/calmodulin complex can activate GPKinase A, which phosphorylates/activates glycogen phosphorylase —> glycogen breakdown

this is useful because when muscles are contracting, you don’t want to have to wait for hormones to kick in to get glycogen breakdown to glucose

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5
Q

Von Gierke’s Disease

A

Glycogen storage disease Type I: glucose-6-phosphatase deficiency (Ia, more common) or glucose transporter deficiency (Ib)

AR, presents 2-6mo —> severe hypoglycemia between meals (lethargy, seizures, lactic acidosis), enlarged liver (excess glycogen accumulates)

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6
Q

what occurs in Type I glycogen storage disease?

A

Von Gierke’s Disease: glucose-6-phosphatase deficiency (Ia, more common) or glucose transporter deficiency (Ib)

AR, presents 2-6mo —> severe hypoglycemia between meals (lethargy, seizures, lactic acidosis), enlarged liver (excess glycogen accumulates)

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7
Q

when and how does Von Gierke’s Disease present?

A

Type I glycogen storage disease: glucose-6-phosphatase deficiency (Ia, more common) or glucose transporter deficiency (Ib)

AR, presents 2-6mo —> severe hypoglycemia between meals (lethargy, seizures, lactic acidosis), protuberant abdomen/ hepatomegaly (excess glycogen accumulates)

also hyperlipidemia (skin xanthomas, high VLDL), gout (uricemia, breakdown product of AMP)

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8
Q

why does lactic acidosis occur in patients with Type I glycogen storage disease?

A

aka Von Gierke’s disease: glucose-6-phosphatase deficiency (Ia, more common)

glucose-6-phosphatase is required for Cori cycle, which converts lactate to glucose in the liver… without it, lactic acid accumulates —> lactic acidosis

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9
Q

AR glycogen storage disease presenting in infancy with severe hypoglycemia between meals, seizures, lactic acidosis, and enlarged liver

what is?

A

Type I glycogen storage disease (Von Gierke’s): glucose-6-phosphatase deficiency (Ia, more common) or glucose transporter deficiency (Ib)

AR, presents 2-6mo —> severe hypoglycemia between meals (lethargy, seizures, lactic acidosis), enlarged liver (excess glycogen accumulates)

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10
Q

Pompe’s Disease

A

Type II glycogen storage disease: alpha-1,4-glucosidase (“lysosomal acid maltase”) deficiency

AR, presents in infancy (severe) —> glycogen accumulates in lysosomes

—> hypertrophy (cardiomegaly, enlarged tongue), hypotonia, liver enlargement (from heart failure - cause of death), cardiomegaly

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11
Q

what occurs in Type II glycogen storage disease?

A

aka Pompe’s Disease: acid alpha-glucosidase (“lysosomal acid maltase”) deficiency

AR, presents in infancy (severe) —> glycogen accumulates in lysosomes

—> hypertrophy (cardiomegaly, enlarged tongue), hypotonia, liver enlargement (from heart failure - cause of death)

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12
Q

when and how does Pompe’s disease present?

A

Type II glycogen storage disease: acid alpha-glucosidase deficiency

AR, presents in infancy (severe) —> glycogen accumulates in lysosomes

—> hypertrophy (cardiomegaly, enlarged tongue), hypotonia, liver enlargement (from heart failure - cause of death)

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13
Q

AR glycogen storage disease presenting in infancy with enlarged muscles (cardiomegaly, enlarged tongue), hypotonia, and liver enlargement secondary to heart failure

what is?

A

Type II glycogen storage disease (Pompe’s): acid alpha-glucosidase (“lysosomal acid maltase”) deficiency

AR, presents in infancy (severe) —> glycogen accumulates in lysosomes

—> hypertrophy (cardiomegaly, enlarged tongue), hypotonia, liver enlargement (from heart failure - cause of death)

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14
Q

Cori’s Disease

A

Type III glycogen storage disease: AR debranching enzyme deficiency

gluconeogenesis is intact, so there is only mild hypoglycemia and glycogen accumulation in muscles (but no lactic acidosis because Cori cycle is intact)

presents in infant/child with hypoglycemia, hepatomegaly, hypotonia, possible cardiomyopathy with hypertrophy

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15
Q

what occurs in Type III glycogen storage disease?

A

aka Cori’s disease: AR debranching enzyme deficiency (alpha-1.6-glucosidase) —> impaired glycogenolysis

gluconeogenesis is intact, so there is only mild hypoglycemia and glycogen accumulation in muscles (but no lactic acidosis because Cori cycle is intact)

presents in infant/child with hypoglycemia, hepatomegaly, hypotonia, possible cardiomyopathy with hypertrophy

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16
Q

how and when does Cori’s Disease present?

A

Type III glycogen storage disease: AR debranching enzyme deficiency

gluconeogenesis is intact, so there is only mild hypoglycemia and glycogen accumulation in muscles (but no lactic acidosis because Cori cycle is intact)

presents in infant/child with hypoglycemia, hepatomegaly, hypotonia, possible cardiomyopathy with hypertrophy

17
Q

AR glycogen storage disease presenting in an infant or child with mild hypoglycemia, hypotonia, and cardiomyopathy with hypertrophy. There is NO lactic acidosis.

What is?

A

Type III glycogen storage disease (Cori’s): AR debranching enzyme deficiency (alpha-1,6-glucosidase)

gluconeogenesis is intact, so there is only mild hypoglycemia and glycogen accumulation in muscles (but no lactic acidosis because Cori cycle is intact)

18
Q

McArdle’s Disease

A

Type V glycogen storage disease: AR muscle glycogen phosphorylase deficiency (myophosphorylase) —> glycogen not properly broken down in muscle

presents adolescence/early adulthood with exercise intolerance, cramps, muscle swelling/weakness, myoglobinuria (dark urine)

19
Q

what occurs in Type V glycogen storage disease?

A

aka McArdle’s Disease: AR muscle glycogen phosphorylase deficiency (myophosphorylase) —> glycogen not properly broken down in muscle

presents adolescence/early adulthood with exercise intolerance, cramps, muscle swelling/weakness, myoglobinuria (dark urine)

20
Q

when and how does McArdle’s Disease present?

A

Type V glycogen storage disease: AR muscle glycogen phosphorylase deficiency (myophosphorylase) —> glycogen not properly broken down in muscle

presents adolescence/early adulthood with exercise intolerance, cramps, muscle swelling/weakness, myoglobinuria (dark urine)

21
Q

AR glycogen storage disease presenting in adolescence or early adulthood with exercise intolerance, cramps, muscle swelling/weakness, and myoglobinuria

what is?

A

Type V glycogen storage disease (McArdle’s): AR muscle glycogen phosphorylase deficiency (myophosphorylase) —> glycogen not properly broken down in muscle

presents adolescence/early adulthood with exercise intolerance, cramps, muscle swelling/weakness, myoglobinuria (dark urine)

22
Q

Type I vs II vs III vs IV vs V glycogen storage disease

A

Type I (Von Gierke’s): glucose-6-phosphatase deficiency —> infancy, severe hypoglycemia + lactic acidosis

Type II (Pompe’s): acid-alpha-glucosidase deficiency (lysosomes) —> infancy (severe), cardiomegaly (HF), enlarged tongue + hypotonia

Type III (Cori’s): debranching enzyme deficiency —> infant/child, mild hypoglycemia + hypotonia

Type IV (Andersen): branching enzyme deficiency —> infantile cirrhosis (glycogen accumulation)

Type V (McArdle’s): myophosphorylase deficiency —> adolescence/early adulthood, exercise intolerance, cramps, myoglobinuria (dark urine)

23
Q

what occurs in Type IV glycogen storage disease?

A

aka Andersen’s: mutation in branching enzyme —> reduced glycogen branching

long unbranched glycogen accumulates in liver —> infantile cirrhosis, early death (<2)

24
Q

Andersen disease

A

Type IV glycogen storage disease: mutation in branching enzyme —> reduced glycogen branching

long unbranched glycogen accumulates in liver —> infantile cirrhosis, early death (<2)

25
Q

what occurs in Type VI glycogen storage disorder?

A

aka Her’s: liver glycogen phosphorylase deficiency

normally-structured glycogen accumulates —> hepatomegaly, fasting hypoglycemia

only liver affected, not muscle

26
Q

Hers disease

A

Type VI glycogen storage disorder: liver glycogen phosphorylase deficiency

normally-structured glycogen accumulates —> hepatomegaly, fasting hypoglycemia

only liver affected, not muscle

27
Q

what occurs in Type VII glycogen storage disease?

A

aka Tarui: deficiency of muscle phosphofructokinase-1

—> reduced exercise tolerance, myoglobinuria, rhabdomyolysis

associated with hemolytic anemia (PFK isozyme of RBC is effected) - remember RBC depend on glycolysis for ATP

unresponsive to glucose administration

28
Q

Tarui disease

A

Type VII glycogen storage disease: deficiency of muscle phosphofructokinase-1

—> reduced exercise tolerance, myoglobinuria, rhabdomyolysis

associated with hemolytic anemia (PFK isozyme of RBC is effected) - remember RBC depend on glycolysis for ATP