Glycogen Metabolism I

Question 1

Why is glucose stored as glycogen?

Answer 1

it minimizes osmotic stress on the cell

Question 2

Why use glycogen for storage in addition to fat?

Answer 2

muscle cannot metabolize fat as rapidly, fat cannot be metabolized in anaerobic conditions, and fat metabolism alone is not adequate to maintain blood glucose levels

Question 3

muscle glycogen

Answer 3

provides quick energy for aerobic or anaerobic metabolism; depleted in less than an hour

Question 4

liver glycogen

Answer 4

reservoir for glucose for other tissues, critical for brain glucose, depleted in 12-24 hours

Question 5

glucose-6-P in muscle cells (from glycogen)

Answer 5

will enter glycolysis pathway

Question 6

glucose-6-P in liver cells (from glycogen)

Answer 6

will be dephosphorylated and released into blood

Question 7

glycogen structure

Answer 7

alpha-1,4 linkage with alpha-1,6 branches

Question 8

Which end of glycogen is glucose added and released?

Answer 8

non-reducing end (OH free at C4)

Question 9

glycogenin

Answer 9

primer for glycogen synthesis by catalyzing the polymerization of the first few glucose molecules

Question 10

glycosome

Answer 10

granules containing both glycogen and enzymes for synthesizing and degrading glycogen

Question 11

glycogen phosphoryase

Answer 11

releases glucose-1-phosphate from glycogen

Question 12

pyridoxal phosphate (vitamin B6)

Answer 12

cofactor for glycogen phosphorylase; acts as general acid catalyst

Question 13

debranching enzyme

Answer 13

cleaves alpha-1,6 O-glycosidic bonds

Question 14

glucose-6-phosphatase

Answer 14

dephosphorylates glucose-6-P for release from liver; located in ER lumen

Question 15

hyperphosphorylated glycogen

Answer 15

degraded by alpha-glucosidase in lysosome

Question 16

phosphoglucomutase

Answer 16

converts glucose-6-P –> glucose-1-P

Question 17

UDP-glucose pyrophosphorylase

Answer 17

converts glucose-1-P –> UDP-glucose

Question 18

first step in glycogen synthesis

Answer 18

transfer of glucose from UDP-glucose to hydroxyl group of Tyr194 on glycogenin (glucotransferase activity)

Question 19

glycogen synthase

Answer 19

transfers glucose from UDP-glucose to non-reducing end of glycogen chain to extend the chain

Question 20

glycogen synthase catalyzes

Answer 20

alpha-1,4 linkages

Question 21

glycogen-branching enzyme

Answer 21

forms alpha-1,6 branches

Question 22

hepatomegaly

Answer 22

accumulation of normal or abnormal glycogen in liver

Question 23

fasting hypoglycemia

Answer 23

defect in glycogen degradation or secretion of glucose from liver

Question 24

glycogen storage disease I (Von Gierke’s)

Answer 24

mutation in glucose-6-phosphatase (1a) or glucose-6-P transporter (1b) which prevents glucose-6-P –> glucose

Question 25

symptoms of Von Gierke’s Disease

Answer 25

affects liver and kidney; severe hypoglycemia between meals, lethargy, seizures, lactic acidosis, liver and kidney enlargement

Question 26

Von Gierke’s treatment

Answer 26

frequent small meals infused with cornstarch to act as slow release of glucose; avoid sucrose, lactose, fructose, and galactose

Question 27

glycogen storage disease II (Pompe’s Disease)

Answer 27

mutation in acid alpha-glucosidase/acid maltose (enzyme in lysosome)

Question 28

Pompe’s Disease symptoms

Answer 28

affects muscle; glycogen accumulates in lysosomes, enlarged muscles (large tongue), hypotonia, liver enlargement from heart failure, no hypoglycemia (liver still breaks down glycogen), death in childhood

Question 29

Pompe’s Disease treatment

Answer 29

enzyme replacement therapy

Question 30

glycogen storage disease III (Cori Disease)

Answer 30

mutation in debranching enzyme

Question 31

Cori Disease symptoms

Answer 31

affects liver and muscle; similar symptoms of Von Gierke’s except has gluconeogenesis and gycogen accumulates both in liver and muscle; abnormal glycogen with short outer chains

Question 32

Cori disease treatment

Answer 32

cornstarch in diet, decrease carbohydrates, increase protein

Question 33

alpha-1,6-glucosidase

Answer 33

debranching enzyme

Question 34

glycogen storage disease IV (Anderson’s)

Answer 34

mutation in branching enzyme

Question 35

Anderson’s disease symptoms

Answer 35

affects liver and muscle; hepatomegaly, cirrhosis, liver failure, myopathy, dilated cardiomyopathy, and abnormal glycogen with long unbranched outer chains

Question 36

Anderson’s disease treatment

Answer 36

liver transplant

Question 37

glycogen storage disease V (McArdle’s)

Answer 37

mutation in glycogen phosphorylase (muscle isozyme)

Question 38

McArdle’s Disease symptoms

Answer 38

affects muscle; glycogen not broken down in muscle cells, no liver problems, exercise intolerance, poor endurance, myoglobinuria, creatine kinase release, brown urine after exercise

Question 39

McArdle’s Disease treatments

Answer 39

avoid intense exercise, vitamin B6 and creatine supplements, and ACE inhibitors

Question 40

glycogen storage disease VI (Hers Disease)

Answer 40

mutation in glycogen phosphorylase (liver isozyme)

Question 41

Hers Disease symptoms

Answer 41

affects liver; hypoglycemia, hepatomegaly, lactic acidosis, hyperlipidemia, short stature

Question 42

Hers Disease treatment

Answer 42

avoid prolonged fasting

Question 43

glycogen storage disease 0

Answer 43

glycogen synthase deficiency

Question 44

glycogen synthase deficiency symptoms

Answer 44

affects liver and muscle; morning fatigue (improved with food), postprandial hyperglycemia (glucose not removed from blood since glycogen not made), and fasting hypoglycemia with ketosis

Question 45

glycogen synthase deficiency treatment

Answer 45

protein rich meals, avoid fasting