M&n Week 1: Glycogen Metabolism

Front 1

Blood glucose can be obtained from which 3 primary sources?

Back 1

1. Diet
2. Glycogenolysis
3. Gluconeogenesis

Front 2

In the absence of a dietary source of glucose, this compound is rapidly released from glycogen stores in found which 2 organs?

Back 2

1. Liver
2. Kidney

Front 3

At what point is gluconeogenesis necessary for the production of glucose?

Back 3

When glycogen stores are depleted

Front 4

Where are the main stores of glycogen in the body found?

Back 4

1. Liver
2. Skeletal muscle

Front 5

How does the function of muscle glycogen differ from the function of liver glycogen?

Back 5

Muscle glycogen --> fuel reserve for the synthesis of ATP during muscle contraction

Liver glycogen --> maintains blood glucose concentration

Front 6

What is glycogen composed of?

Back 6

alpha-D-glucose

Front 7

What happens to liver glycogen stores during the well-fed state?

Back 7

Glycogen stores increase

Front 8

T or F

Muscle glycogen is not affected by short periods of fasting (a few days).

Back 8

TRUE

Also, muscle glycogen is only moderately decreased in prolonged fasting (weeks).

*Fasting has a much greater affect on liver glycogen stores

Front 9

Where does the process of glycogenesis take place?

Back 9

Cytosol

Front 10

List 5 enzymes involved in glycogenesis.

Back 10

1. Phosphoglucomutase
2. UDP-glucose phosphorylase
3. Glycogenin
4. Glycogen synthase
5. "Branching enzyme" (amylo-a(1-4) --> a(1-6) transglucosidase)

Front 11

Which enzyme converts Glucose-6-PO4 to Glucose-1-PO4?

Back 11

Phosphoglucomutase

Front 12

Which enzyme produces UDP-Glucose?

Back 12

UDP-glucose phosphorylase

(Glucose-1-PO4 + UTP --> UDP-glucose + PPi)

Front 13

Which protein performs autoglucosylation to produce a primer for glycogenesis?

Back 13

Glycogenin

(Production of a primer is necessary because glycogen synthase cannot initiate chain synthesis)

Front 14

Which enzyme elongates the glycogen chain during glycogenesis?

Back 14

Glycogen synthase

*Creates a(1-->4) linkages

Front 15

Which enzyme adds branching points to the glycogen chain during glycogenesis?

Back 15

"Branching enzyme" (4:6 transferase)

aka: amylo-a(1-->4)-a(1-->6) transglucosidase

*Transfers chain of 6-8 glucosyl residues from the nonreducing end of the glycogen chain, breaking an a(1-->4) bond and attaches it by an a(1-->6) linkage.

Front 16

T or F

A completely separate set of cytosolic enzymes is required for glycogenolysis than is required for glycogenesis.

Back 16

TRUE

Front 17

Which two enzymes are involved in glycogenolysis?

Back 17

1. Glycogen phosphorylase
2. Debranching enzyme (4:4 transferase activity AND 1:6 glucosidase activity)

Front 18

Which enzyme sequentially cleaves a(1-->4) glycosidic bonds at the nonreducing ends by phosphorolysis?

How many glucosyl units remain on each chain before a branch point?

Back 18

Glycogen phosphorylase

4 glucosyl units remain

Front 19

Describe the 2 functions of the debranching enzyme in glycogenolysis.

Back 19

1. 4:4 transferase activity: removes the outer THREE of the 4 glucosyl residues attached at a branch and transfers them to the nonreducing end of another chain

2. 1:6 glucosidase activity: removes the remaining single glucose residue attached in an a(1-->6) linkage via hydrolysis.

Front 20

How is Glucose-6-PO4 converted to glucose?

Back 20

This reaction is performed in the liver.
First, G-6-PO4 is translocated into the ER by Glucose-6-PO4 translocase.
Glucose 6-phosphatase then converts it to glucose.

Front 21

In which organ is glucose-6-phosphotase located?

Back 21

Liver
This enzyme converts G-6-PO4 to glucose.

It is NOT located in muscle, so G-6-PO4 enters glycolysis rather than getting converted to glucose

Front 22

Which enzyme is deficient in the Type II glycogen storage disease, Pompe disease?

Which organs are affected?

Back 22

lysosomal a(1-->4)-glucosidase

Primarily liver, heart, and muscle

Front 23

Which glycogen storage disease results in massive cardiomegaly?

Back 23

Type II: Pompe's disease

(Excessive glycogen concetrations found in abnormal vacuoles in the lysosomes)

Front 24

Which glycogen storage disease results in increased muscle glycogen that cannot be broken down, leading to painful muscle cramps and myoglobinuria with strenuous exercise?

Back 24

Type V: McArdle Syndrome

*Also, no rise in blood lactate during strenuous exercise

Front 25

Which enzyme is deficient in McArdle's disease (Type V)?

Back 25

Skeletal muscle glycogen phosphorylase
(myophosphorylase)

(*liver enzyme is normal)

Front 26

Which enzyme is deficient in Von Gierke disease (Type 1a)?

What about Type 1b?

Back 26

Type 1a --> Glucose 6-phosphatase deficiency

Type 1b --> Glucose 6-phosphate translocase

Front 27

Which glycogen storage disease results in severe fasting hypoglycemia, increased liver glycogen, increased blood lactate, and hepatomegaly?

Back 27

Von Gierke's disease (Type 1)

Front 28

Which glycogen storage disease is the only one that is also a lysosomal storage disease?

Back 28

Pompe's disease

Front 29

Which substrate(s) allosterically activate glycogenesis?

Back 29

Glucose 6-phosphate

Front 30

Which substrate(s) allosterically inhibit glycogenolysis?

Back 30

1. Glucose 6-phosphate
2. ATP
3. Glucose (in liver)

Front 31

Which compounds allosterically activate glycogenolysis?

Back 31

1. AMP
2. Ca2+

*This activation occurs in muscle, but not in the liver

Front 32

What is the effect of Glucose 6-PO4 on glycogen metabolism?

What enzyme is being activated?

Back 32

Activates glycogenesis and inhibits glycogenolysis

*Glycogen synthase is activated

Front 33

What is the effect of AMP on glycogen metabolism?

What enzyme is being activated?

Back 33

AMP activates glycogenolysis

*Glycogen phosphorylase is activated

Front 34

What is the effect of ATP on glycogen metabolism?

Back 34

ATP inhibits glycogenolysis

Front 35

What is the effect of Ca2+ on glycogen metabolism?

What enzyme is being activated?

Back 35

Ca2+ activates glycogenolysis

*Glycogen phosphorylase is activated

Front 36

Which substrate activates glycogen synthase and inhibits glycogen phosphorylase?

Back 36

Glucose 6-PO4

Front 37

In the liver, which substrate serves as the key allosteric inhibitor of glycogen phosphorylase?

Back 37

Glucose

Front 38

Which hormones stimulate glycogen degradation?

Back 38

1. Glucagon
2. Epinephrine

Front 39

Is glycogen phosphorylase kinase activated or inactivated by phosphorylation?

Back 39

Activated

Front 40

Is glycogen synthase activated or inactivated by phosphorylation?

Back 40

Activated

Front 41

What is the result of high levels of cAMP on glycogen metabolism?

Back 41

High levels of cAMP results in glycogen degradation

Front 42

How is glycogen phosphorylase kinase activated?

What is the function of this enzyme?

Back 42

Activated via phosphorylation by cAMP-dependent protein kinase A

*Once activated, this enzyme phosphorylates/activates glycogen phosphorylase --> resulting in glycogen degradation

Front 43

How is glycogen phosphorylase activated, and what is the result?

Back 43

Activated by glycogen phosphorylase kinase via phosphorylation

*Result is glycogen degradation

Front 44

How is glycogen phosphorylase inactivated?

Back 44

Hydrolysis of its phosphate group by Protein phosphatase 1

Front 45

If glucose is bound to muscle glycogen phosphorylase b in the presence of AMP, what will be the result?

Back 45

The inhibitory effect of glucose trumps the activating effect of AMP.

Front 46

How does insulin indirectly affect glycogen phosphorylase in the muscle?

Back 46

Insulin indirectly inhibits glycogen phosphorylase by increasing the uptake of glucose, leading to an increased level of G-6-PO4 which allosterically inhibits the enzyme

Front 47

How is glycogen phosphorylase b activated without being phosphorylated?

Back 47

AMP activates the enzyme w/o phosphorylating it

(Glycogen phosphorylase kinase activates it via phosphorylation)

Front 48

Is glycogen synthase activated or inactivated by phosphorylation?

Back 48

Inactivated

(*This differs from glycogen phosphorylase kinase and glycogen phosphorylase, which are both activated by phosphorylation)

Front 49

What is the effect of Protein phosphatase 1 on glycogen synthase?

Back 49

Activates glycogen synthase --> glycogen synthesis

*Glycogen synthase is activated by dephosphorylation

Front 50

What is the effect of Protein phosphatase 1 on glycogen phosphorylase?

Back 50

Inactivates glycogen phosphorylase --> inhibits glycogen degradation

*Glycogen phosphorylase is inactivated by dephosphorylation

Front 51

What is the effect of protein kinase A on glycogen synthase?

Back 51

Inactivation

*Glycogen synthase is inactivated by phosphorylation

Front 52

Which enzyme activates glycogen synthase and inhibits glycogen phosphorylase?

Back 52

Protein phosphatase 1

Front 53

Which enzyme inactivates glycogen synthase and activates glycogen phosphorylase?

Back 53

Protein kinase A

Front 54

Are glycogen stores utilized in the early or late stages of fasting?

Back 54

Early stages

Front 55

Which enzyme illustrates an overlap between gluconeogenesis and glycogen degradation?

Back 55

Glucose 6-phosphatase

Front 56

T or F

Glycogen synthesis and degradation are regulated by different hormonal signals

Back 56

FALSE

Synthesis and degradation are reciprocally regulated by the same hormonal signals
(Elevated insulin = activates glycogenesis and inhibits glycogenolysis; Glucagon and Epinephrine = inhibit glycogenesis and activated glycogenolysis)