Biochem - Metabolism (Glycogen regulation & associated Clinical Correlations)

Question 1

What 3 substances/factors regulate glycogen?

Answer 1

Glycogen regulation by insulin and glucagon/epinephrine

Question 2

Where in the body does insulin regulate glycogen, and how does this process work?

Answer 2

Insulin (liver and muscle); Insulin stimulates TYROSINE KINASE RECEPTOR, which stimulates GLYCOGEN SYNTHASE to synthesis glycogen and PROTEIN PHOSPHATASE to inhibit Glycogen phosphorylase (preventing the release of glucose from glycogen)

Question 3

Where in the body does glucagon regulate glycogen, and how does this process work?

Answer 3

Glucagon (liver); Glucagon stimulates the GLUCAGON RECEPTOR, which signals through ADENYLYL CYCLASE to produce cAMP from ATP, stimulating PROTEIN KINASE A to stimulate GLYCOGEN PHOSPHORYLASE KINASE, which stimulates GLYCOGEN PHOSPHORYLASE to release glucose from glycogen

Question 4

Where in the body does epinephrine regulate glycogen? At each location, through which receptor does epinephrine signal?

Answer 4

Epinephrine (liver and muscle) - Beta receptor; Epinephrine (liver) - Alpha receptor

Question 5

Where in the body does epinephrine regulate glycogen through Beta receptors? What is the process by which this regulation occurs?

Answer 5

Epinephrine (liver and muscle) - Beta receptor; BETA RECEPTOR (like the glucagon receptor) signals through ADENYLYL CYCLASE, which stimulates production of cAMP from ATP, stimulating PROTEIN KINASE A, which stimulates GLYCOGEN PHOSPHORYLASE KINASE, which stimulates GLYCOGEN PHOSPHORYLASE to release glucose from glycogen

Question 6

Where in the body does epinephrine regulate glycogen through Alpha receptors? What is the process by which this regulation occurs?

Answer 6

Epinephrine (liver) - Alpha receptor; ALPHA RECEPTOR triggers the ENDOPLASMIC RETICULUM to release CALCIUM, which directly stimulates GLYCOGEN PHOSPHORYLASE KINASE as well as joins the calcium-calmodulin complex in muscle during contraction, which also stimulates glycogen phosphorylase kinase. Stimulation of glycogen phosphorylase kinase stimulates GLYCOGEN PHOSPHORYLASE to release glucose from glycogen

Question 7

What kinds of bonds do the branches and linkages of glycogen have?

Answer 7

Branches have alpha-(1,6) bonds; Linkages have alpha-(1,4) bonds

Question 8

What happens to glycogen in the skeletal muscle during exercise?

Answer 8

Glycogen undergoes glycogenolysis => glucose-1-phosphate => glucose-6-P, which is rapidly metabolized during exercise

Question 9

What happens to glycogen in hepatocytes? Under what circumstance is it broken down?

Answer 9

Glycogen is stored and undergoes glycogenolysis to maintain blood sugar at appropriate levels

Question 10

What is the process by which glycogenolysis occurs in hepatocytes?

Answer 10

GLYCOGEN PHOSPHORYLASE cleaves glucose-1-P residues off branched glycogen until four remain before a branch point. The 4-ALPHA-D-GLUCANOTRANSFERASE (debranching enzyme) moves three glucose-1-Ps from the branch to the linkage. Then ALPHA-1,6-GLUCOSIDASE (debranching enzyme) cleaves off the last glucose 1-P on the branch.

Question 11

What is “limit dextrin”?

Answer 11

“Limit dextrin” refers to one to four residues remaining on a branch after glycogen phosphorylase has already shortened it

Question 12

Draw a diagram depicting the synthesis and breakdown of glycogen, including and labeling the reactions of the following enzymes: (1) UDP-glucose pyrophosphorylase (2) Glycogen synthase (3) Branching enzyme (4) Glycogen phosphorylase (5) Debranching enzyme (4-alpha-D-glucanotransferase) (6) Debranching enzyme (alpha-1,6-glucosidase).

Answer 12

See p. 113 in First Aid 2014 for visual near top middle of page

Question 13

What role may lysosomes play related to glycogen, and what enzyme is involved in this?

Answer 13

A small amount of glycogen is degraded in lysosomes by alpha-1,4-glucosidase (acid maltase)

Question 14

How many types of glycogen storage diseases are there? What are the general metabolic outcomes that all share?

Answer 14

12 types, all resulting in abnormal glycogen metabolism and an accumulation of glycogen within cells

Question 15

What are 4 important examples of glycogen storage diseases?

Answer 15

(1) Von Gierke disease (Type I) (2) Pompe disease (Type II) (3) Cori disease (Type III) (4) McArdle disease (Type V)

Question 16

What are 4 clinical findings of Von Gierke disease (type I)?

Answer 16

(1) Severe fasting hypoglycemia, (2) Very high glycogen in liver, (3) High blood lactate,(4) Hepatomegaly

Question 17

What enzyme is deficient in Von Gierke disease (type I)?

Answer 17

Glucose-6-phosphatase

Question 18

What are 2 general clinical findings of Pompe disease (type II)? What outcome do they have?

Answer 18

Cardiomyopathy and Systemic findings leading to early death; Think: “Pompe trashes the Pump (heart, liver, and muscle)”

Question 19

What enzyme is deficient in Pompe disease (type II)?

Answer 19

Lysosomal alpha-1,4-glucosidase (acid maltase)

Question 20

To what other glycogen storage disease is Cori disease (type III) clinically similar, and how so? What clinical finding is used to distinguish it?

Answer 20

Milder form of type I (von Gierke disease) with normal blood lactase levels (unlike von Gierke disease, which has high blood lactate)

Question 21

What enzyme is deficient in Cori disease (type III)?

Answer 21

Debranching enzyme (alpha-1,6-glucosidase)

Question 22

What are 3 clinical findings of McArdle disease (type V)? What is the underlying general mechanism behind them?

Answer 22

Increase glycogen in muscles, but cannot break it down, leading to (1) painful muscle cramps, (2) myoglobinuria (red urine) with strenuous exercise, and (3) arrhythmia from electrolyte abnormalities; Think: “McArdle = Muscle”

Question 23

What is the deficient enzyme in McArdle disease (type V)?

Answer 23

Skeletal muscle glycogen phosphorylase (myophosphorylase); Think: “McArdle = Muscle”

Question 24

What is the mode of inheritance of Von Gierke disease (type I)?

Answer 24

Autosomal recessive

Question 25

What is the treatment for von Gierke disease (type I)?

Answer 25

Treatment: Frequent oral glucose/cornstarch; Avoids of fructose and galactose

Question 26

What is the mode of inheritance of Pompe disease (type II)?

Answer 26

Autosomal recessive

Question 27

What is the mode of inheritance of Cori disease (type III)?

Answer 27

Autosomal recessive

Question 28

What happens to gluconeogenesis in Cori disease (type III)?

Answer 28

Gluconeogenesis is intact

Question 29

What is the mode of inheritance McArdle disease (type IV)?

Answer 29

Autosomal recessive