Glycogen Storage Diseases

Front 1

What is, generally speaking, a storage disease?

Back 1

- Inborn genetic error
- Characterized by storage of abnormal amounts of carbs or lipids in cells
- Decreased ability to break down a compound

Front 2

How are storage diseases inherited?

Back 2

- Tend to be autosomal recessive
- Tend to be lysosomal

Front 3

Ia (von Gierke Disease)

Back 3

G-6-Phosphatase
- G-6-Pase is in the ER, helps remove the phosphate to convert to glucose to raise BGL
- Severe fasting hypoglycemia
- Hyperuricemia, hyperlipidemia

Front 4

Ib (von Gierke Disease)

Back 4

ER G-6-Phosphatase transporter
- Deficiency in the transporter
- Hyperurecemia, hyperlipidemia, fasting hypoglycemia

Front 5

II (Pompe Disease)

Back 5

Lysosomal acid alpha glucosidase
- Normally degrades 1,4/1,6 linkages in glycogen - glycogen accumulates
- Cardiomegaly, muscle weakness, death
- Because it's lysosomal, affects *ALL* cells even though degridation is only 3% done by lysosomes

Front 6

III (Cori Disease, Limit Dextrinosis)

Back 6

Debranching Enzyme
- Can't get rid of 1,6 linkages
- Abnormal glycogen structure
- Muscle weakness, hyperlipidemia, hepatomegaly.. same as Ia/Ib

Front 7

IIIa, IIIb

Back 7

- IIIa Affects Liver and Muscle
- IIIb Affects only liver

Front 8

IV (Anderson Disease)

Back 8

**LIVER**
- Branching Enzyme
- Cannot make 1,6 linkages, so glycogen structure is highly linear
- Low solubility lets it build up in the tissue
- Can still break it down, but not a benign disease
- Hepatomegaly, cardiomegaly, death

Front 9

V (McArdle Disease)

Back 9

**MUSCLE** Phosphorylase
- Normally breaks down glycogen into G1P and the continuing chain
- Can't use glucose to make ATP, don't get lactate buildup
- Exercise intolerance, cramps

Front 10

VI (Hers Disease)

Back 10

**LIVER** Phosphorylase
- Can't properly break down glycogen
- Hepatomegaly, fasting hypoglycemia mild

Front 11

VII (Tauri Disease)

Back 11

- **MUSCLE** PFK
- Catalyzes normally F6P to F1,6bP, leads to the accumulation of G6P, which activates glycogen synthesis
- PFK is a tetramer
- Similar to V but more severe exercise intolerance and cramps

Front 12

Which diseases affect the liver?

Back 12

I, III, IV, VI

Front 13

Which diseases affect muscle?

Back 13

V, VII

Front 14

Glycogen Synthase

Back 14

- Transfers glucose from UDP-Glucose to a glycogen primer, makes alpha 1,4 bonds
- Activated by high levels of G6P, insulin

Front 15

Branching Enzyme

Back 15

- Creates alpha 1,6 linkages for branching
- Decreases solubility
- Deficent in: IV (Liver)

Front 16

Glycogen Phosphorylase

Back 16

- Sequential breakdown of glycogen to make G1P from 1,4 until it hits limit dextrin (the 1,6 linkages)
- Activated by glucagon, calcium (need energy) and AMP (muscle)
- Deficent in: V, VI

Front 17

Debranching Enzyme

Back 17

- Bifunctional protein removing 1,4 and 1,6 linkages
- Creates G1P and free glucose
- Deficent in: III

Front 18

Glucose-6-Phosphatase

Back 18

- Removes phosphate from G6P to make free glucose
- Present only on the ER, liver only
- Deficent: in Ia, Ib