Glycogen synthesis, breakdown and glycogen storage diseases.

Question 1

This molecule represents the comitted step of glycogenesis:

Answer 1

Glucose-1-phosphate

Question 2

Which enzyme catalyzes the first few glycosydic bonds between glucose molecules during glycogenesis ?

Answer 2

Glycogenin

Question 3

What kind of bonds does glycogen synthase make :

Answer 3

a (1–>4) glycosidic bonds

Question 4

What is the role of branching enzyme ?

Answer 4

Branching enzyme : cuts the a(1->4) glycosidic bonds and makes a (1->6) bonds during the synthesis of glycogen from glucose-1-phosphate.

Also called 4,6 transferase because it transferers the glycosidic bond from the 4th to the 6th position.

Question 5

Regarding glycogenolysis, which enzyme cuts a (1->4) glycosidic bonds until 4 glucosyl units remain on each chain before the branching point ?

Answer 5

Glycogen phosphorylase

Question 6

Glycogen phosphorylase uses what as a coenzyme ?

Answer 6

Vitamin B6 (pyridoxal phosphate)

Question 7

What is the molecule produced as a result of the action of glycogen phosphorylase ?

Answer 7

Limit dextrin

Question 8

What is the main enzyme of glycogenolysis that releases glucose-1-phopshate in great amount ?

Answer 8

Glycogen phosphorylase

Question 9

Breaks (1–>4) , Makes (1–>4) then breaks (1–>6) releasing free glucose during glycogenolysis :

Answer 9

Debranching enzyme

Question 10

Glucose-1-phosphate can be converted back to glucose-6-phosphate by phosphoglucomutase and then to glucose by glucose-6-phosphatase. What tissue lacks glucose-6-phosphatase, preventing it from contributing to blood glucose levels ?

Answer 10

Muscles

Glucose-6-phosphatase can only be found in the liver & kidneys.

Question 11

Glycogenolysis and gluconeogenesis pathway share this common enzyme:

Answer 11

Glucose-6-phosphatase

Question 12

When there is no external source of glucose (food) what mechanism comes in first to prevent hypoglycemia ?

Answer 12

Glycogenolysis

Gluconeogenesis is a more efficient process to maintain blood glucose in cases of starvation, but the process is longer to kick in.

Question 13

Regulators of glycogen metabolism in the liver :

Answer 13

Insulin/Glucagon
Epinephrine
Hypoglycemia

Question 14

Regulators of glycogen metabolism in the muscle :

Answer 14

Epinephrine
High AMP ; Low ATP
Ca2+

Anytime the muscle contracts, Ca2+ is released.

Question 15

Glucagon & Epinephrine effects :

Answer 15

Activation of glycogen phosphorylase via GPCR signaling pathway using cAMP and protein kinase A as intermediate.

Note that protein kinase A phosphorylates specific serine & threonine residues.

Question 16

Effects of insulin on glycogen metabolism :

Answer 16

Activates glycogen synthase using phosphoprotein phosphatase as an intermediate.

Stimulates phosphodiesterase which converts cAMP to 5’AMP which antagonizes the effects induced by glucagon/epi.

Question 17

Glycogen storage diseases resulting from deficiency in glucose-6-phosphatase ?

Answer 17

Von Gierke’s disease

Without this enzyme, there is no release of free glucose from liver cells.

Question 18

Typical presentation of pts affected with Von Gierke’s disease ?

Answer 18

Severe hypoglycemia
Hepatomegaly
Hyperuricemia
Hyperlipidemia
Lactic acidosis

Usually by 6 months of age, when baby’s meals start to be more spaced out.

Question 19

Treatment of von Gierke’s disease ?

Answer 19

Avoid fasting
Small frequent meals
Avoidance of fructose and lactose (not readily available sources of glucose).

Question 20

Pompe’s disease refers to deficiency in what enzyme ?

Answer 20

Lysosomal 1,4 glucosidase (acid maltase)

Question 21

What is the presentation and consequences of Juvenile onset of Pompe’s disease ?

Answer 21

Glycogen accumulation in lysosomes causes cardiomegaly and hypotonia. Usually, pt dies by age 2 years old.

Question 22

Condition that results from lack of debranching enzyme where bx shows limit dextrin ?

Answer 22

Cori’s disease (aka Forbe’s)

Liver & muscle debranching enzyme deficiency.

Question 23

Glycogen storage disease that results in abnormal glycogen structure ?

Answer 23

Cori’s disease

Question 24

Glycogen storage disease that results in severe hypoglycemia?

Answer 24

Von Gierke’s

Gluconeogenesis is affected.

Question 25

Glycogen storage disease that results in mild hypoglycemia ?

Answer 25

Cori’s disease

Gluconeogenesis is unaffected.

Question 26

McArdle’s disease results from a deficiency in what enzyme ?

Answer 26

Glycogen phosphorylase (myophosphorylase)

Inability to mobilize glucose in the muscle i.e. can’t break down glycogen in the muscle.

Question 27

Presentation of pts with McArdle’s :

Answer 27

Symptoms appear at onset of exercise:
Cramps
Myoglobinuria
Lactic acid levels post exercise lower than normal limits

Question 28

Low levels of plasma lactate after exercise, elevated CK without hypoglycemia is indicative of ?

Answer 28

McArdle’s

Question 29

Problem with hepatic glucose phosphorylase, presenting as a milder version of Von Gierke’s ?

Answer 29

Her’s disease