Glycogen B&B Flashcards
what 3 enzymes are required to divert glucose-6-phosphate into synthesis of branched glycogen?
- UDP-glucose pyrophosphorylase
- glycogen synthase (alpha1,4 linkages)
- branching enzyme (alpha1,6 linkages)
what 3 enzymes are required for glycogen breakdown?
- glycogen phosphorylase (alpha1,4 linkages)
- debranching enzyme (alpha1,6 linkages)
- alpha1,4 glucosidase (lysosomes)
how does phosphorylation control the activity of glycogen synthase vs glycogen phosphorylase?
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
during periods of muscle contraction, glycogen phosphorylase can be phosphorylated/activated in the absence of hormones (glucagon, epinephrine) by ______
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
Von Gierke’s Disease
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)
what occurs in Type I glycogen storage disease?
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)
when and how does Von Gierke’s Disease present?
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)
why does lactic acidosis occur in patients with Type I glycogen storage disease?
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
AR glycogen storage disease presenting in infancy with severe hypoglycemia between meals, seizures, lactic acidosis, and enlarged liver
what is?
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)
Pompe’s Disease
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
what occurs in Type II glycogen storage disease?
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)
when and how does Pompe’s disease present?
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)
AR glycogen storage disease presenting in infancy with enlarged muscles (cardiomegaly, enlarged tongue), hypotonia, and liver enlargement secondary to heart failure
what is?
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)
Cori’s Disease
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
what occurs in Type III glycogen storage disease?
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
how and when does Cori’s Disease present?
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
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?
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)
McArdle’s Disease
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)
what occurs in Type V glycogen storage disease?
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)
when and how does McArdle’s Disease present?
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)
AR glycogen storage disease presenting in adolescence or early adulthood with exercise intolerance, cramps, muscle swelling/weakness, and myoglobinuria
what is?
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)
Type I vs II vs III vs IV vs V glycogen storage disease
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)
what occurs in Type IV glycogen storage disease?
aka Andersen’s: mutation in branching enzyme —> reduced glycogen branching
long unbranched glycogen accumulates in liver —> infantile cirrhosis, early death (<2)
Andersen disease
Type IV glycogen storage disease: mutation in branching enzyme —> reduced glycogen branching
long unbranched glycogen accumulates in liver —> infantile cirrhosis, early death (<2)
what occurs in Type VI glycogen storage disorder?
aka Her’s: liver glycogen phosphorylase deficiency
normally-structured glycogen accumulates —> hepatomegaly, fasting hypoglycemia
only liver affected, not muscle
Hers disease
Type VI glycogen storage disorder: liver glycogen phosphorylase deficiency
normally-structured glycogen accumulates —> hepatomegaly, fasting hypoglycemia
only liver affected, not muscle
what occurs in Type VII glycogen storage disease?
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
Tarui disease
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
