Lecture 23 (Exam 2)

Question 1

What are the two rate limiting steps of glycogen synthesis and degradation, respectively?

Answer 1

Glycogen synthase

Glycogen phosphorylase

Question 2

Both glycogen rate limiting steps are regulated by ________ regulators and reversible __________ (under the control of hormones), but effects are in opposite directions.

Answer 2

Allosteric

Phosphorylation

Question 3

The key enzyme of glycogen synthesis is glycogen synthase. It exists in two forms, which are…

Answer 3

Active non-phosphorylated “a” form

Inactive phosphorylated “b” form

Question 4

Glycogen synthase is phosphorylated by…

Answer 4

Glycogen synthase kinase (GSK)

Question 5

GSK is under the control of ________ and ________.

Answer 5

Insulin

PKA (Protein kinase A)

Question 6

Allosteric regulation of glycogen synthase is done by __________, which is a powerful activator and stabilizes the active form.

Answer 6

Glucose 6-phosphate

Question 7

Glycogen phosphorylase (key enzyme of glycogen breakdown) exists in 2 forms, which are…

Answer 7

Active “a” form (R relaxed state) - in liver

Inactive “b” form (T tense state) - in muscle

Question 8

Liver and muscle forms of glycogen phosphorylase are products of separate genes, called _______. They differ in their sensitivities to regulatory molecules.

Answer 8

Isozymes

Question 9

Liver enzyme (GP) is inactivated by free ________ (indicator of blood sugar levels), and is unaffected by ______.

Answer 9

Glucose

AMP

Question 10

Muscle form (GP) is allosterically activated by ______ (measure of low energy status of cell).

Answer 10

AMP

Question 11

Mutation in liver GP causes what disease?

Answer 11

Hers disease

Question 12

Mutation in muscle GP causes what disease?

Answer 12

McArdle syndrome

Question 13

GP is in its default “a” form or active form in the liver, and is inactivated by…

Answer 13

Glucose

Question 14

Glucose binds to the active site of GP and stabilizes conformation in the inactive _____ state. When glucose levels are high, no need for glycogen breakdown (which will make more glucose).

Answer 14

T

Question 15

GP is in its default “b” form or inactive form in the muscle, and is activated by…

Answer 15

AMP

Question 16

AMP binds to the active site of GP and stabilizes the conformation of “b” into the active _____ state.

Answer 16

R

Question 17

During muscle contraction _______ is converted to AMP by myosin and adenylate kinase signaling the GP to breakdown glycogen.

Answer 17

ATP

Question 18

What are the negative allosteric regulators of muscle GP?

Answer 18

ATP

Glucose 6-phosphate

Question 19

Under normal physiological conditions, GP is (ACTIVE/INACTIVE) in the muscle because of inhibitory effect of ATP and Glucose 6-phosphate.

Answer 19

Inactive

Question 20

Glycogenesis is favored in the fed state. What three things are high?

Answer 20

Blood glucose high
Insulin high
Cellular ATP high (high energy)

Question 21

When glycogen synthesis is favored, glycogen synthase is (PHOSPHORYLATED/DEPHOSPHORYLATED).

Answer 21

Dephosphorylated (active form)

Question 22

When glycogen synthesis is favored, glycogen phosphorylase is (PHOSPHORYLATED/DEPHOSPHORYLATED).

Answer 22

Dephosphorylated (inactive form)

Question 23

Glycogenolysis is favored in fasting state. What is low and what is high during this?

Answer 23

Blood glucose low
Glucagon high (makes liver from glycogen to glucose)

Question 24

Glycogenolysis is also favored during exercise. What is high during this?

Answer 24

Cellular calcium high (in exercising muscles) 
AMP high (from breakdown of ATP)

Question 25

When glycogen breakdown is favored, glycogen synthase is (PHOSPHORYLATED/DEPHOSPHORYLATED).

Answer 25

Phosphorylated (inactive form)

Question 26

When glycogen breakdown is favored, glycogen phosphorylase is (PHOSPHORYLATED/DEPHOSPHORYLATED).

Answer 26

Phosphorylated (active form)

Question 27

High blood glucose promotes glycogen synthesis. This causes a release of insulin by the ______ of the pancreas. The insulin then binds to its receptor ______ ______, where this causes activation of a signaling cascade.

Answer 27

Beta cells | Tyrosine kinase

Question 28

What are the 4 key proteins involved in glycogen synthesis regulation by insulin?

Answer 28

GLUT4 Protein kinase B (PKB) Protein phosphatase 1 (PP1) Glycogen synthase kinase 3 (GSK3)

Question 29

In the mechanism of regulation by insulin, put the following steps in order -- A. Activation of PKB B. PKB phosphorylates PP1 (activate) and GSK3 (inactivate) C. Active PP1 dephosphorylates glycogen synthase (activate) and dephosphorylates glycogen phosphorylase (inactivate) D. Formation of the insulin receptor complex E. Translocation of GLUT4 to membrane

Answer 29

1. D 2. A 3. E 4. B 5. C ***Study slide 12

Question 30

This disease is caused by reduced sensitivity to insulin, called insulin resistance. There are mutations in the insulin receptor and/or downstream signaling proteins.

Answer 30

Type 2 diabetes

Question 31

Type 2 diabetes down-regulation in receptor levels can be caused by -- - - Triggered by elevated _______ - - Endocytosis and degradation of the insulin receptor - - Defective receptors not replaced by ________

Answer 31

Insulin | Translation

Question 32

Blood glucose criteria for -- Normal fasting and fed? Pre diabetic/at risk fasting and fed? Diabetes mellitus fasting and fed?

Answer 32

70-100 mg/dL (fasting) -- 140 mg/dL (fed) 100-125 mg/dL (fasting) -- Greater than 140 mg/dL (fed) 126 mg/dL (fasting) -- 199 mg/dL (fed)

Question 33

Hormonal control of glycogen phosphorylase --- -- Low blood sugar levels release ________ (acts on liver) which are made by alpha cells of pancreas -- Muscle activity releases _______ (effects are on muscle)

Answer 33

Glucagon | Epinephrine

Question 34

The effects of both hormones (glucagon and epinephrine) are mediated via _______. They signal glycogen breakdown.

Answer 34

GPCR (G protein coupled receptors)

Question 35

The phosphorylation of a single _______ residues converts b to a. Conversion is initiated by hormones and the phosphorylating itself is carried out by _________ _________.

Answer 35

``` Serine Phosphorylase kinase (PK) ```

Question 36

In regulation by glucagon, blood glucose levels are low (promote glycogen breakdown). Alpha cells of the pancreas release _______, where it goes on to bind to ______ on hepatocytes. This triggers a signaling cascade.

Answer 36

Glucagon | GPCR

Question 37

What are the key enzymes and second messengers for regulation by glucagon?

Answer 37

``` G protein Adenylate cyclase (AC) and cAMP Protein kinase (PKA) Protein phosphatase 1 (PP1) Phosphorylase kinase (PK) ```

Question 38

For regulation by glucagon, put the following steps in order -- A. PKA phosphorylates PK (activate) B. Activates PKA C. PKA phosphorylates an inhibitor which inactivates PP1 D. Activates AC which forms cAMP E. Binding of glucagon to its GPCR turns on G protein F. PKA phosphorylates glycogen synthase (inactivates) G. Active PK phosphorylates glycogen phosphorylase (activates)

Answer 38

1. E 2. D 3. B 4. F 5. A 6. C 7. G ***Study slide 18

Question 39

This hormone creates a fight or flight response. It is released by adrenal glands and promotes degradation of glycogen in a pathway similar to glucagon.

Answer 39

Epinephrine

Question 40

Epinephrine allosteric regulators -- _________ -- activates glycogen synthase. Inactivates glycogen phosphorylase _________ -- inhibits glycogen phosphorylase in liver but not muscle ________ -- activates glycogen phosphorylase kinase ________ -- activates glycogen phosphorylase (especially relevant during periods of exercise)

Answer 40

Glucose 6-phosphate Free glucose Ca++ AMP

Question 41

There is an "off" switch of glycogen breakdown. It occurs when secretion of hormone stops. PK and GP are _________ and inactivated, breakdown of glycogen stops, and synthesis of glycogen is promoted.

Answer 41

Dephosphorylated

Question 42

Glucagon (DOES/DOES NOT) act on muscle.

Answer 42

Does not (only liver)

Question 43

In the liver Glu-1-P is converted to _______ and then to glucose by ______. Free glucose is then released into the blood stream.

Answer 43

Glu-6-P | Glucose-6-Phosphatase

Question 44

Myocytes in the skeletal and cardiac cycle muscle lack _________ and hence cannot hydrolyze Glu-6-P. They use it to generate energy via glycolysis and TCA cycle.

Answer 44

Glucose-6-phosphatase

Question 45

What is the glucose sensor in liver cells?

Answer 45

Glycogen phosphorylase (GP)

Question 46

Name the following glycogen storage disease based on the characteristics -- Defective -- Glucose-6-phosphatase OR transport system Organ affected -- Liver and kidney Glycogen in the affected organ -- Increased amount; normal structure

Answer 46

GSD 1 -- Von Gierke

Question 47

Name the following glycogen storage disease based on the characteristics -- Deficiency in glycogen synthase Patients cannot synthesize glycogen Have muscle cramps due to lack of glycogen in muscle Rely on glucose in diet Vulnerable to hypoglycemia when fasting (during sleep) Need to eat frequently

Answer 47

GSD 0

Question 48

Name the following glycogen storage disease based on the characteristics -- Defective enzyme -- alpha-1,4-Glucosidase (lysosomal) Organ affected -- all organs Glycogen in the affected organ -- Massive increase in amount; normal structure

Answer 48

GSD II -- Pompe

Question 49

Name the following glycogen storage disease based on the characteristics -- Defective enzyme -- Deficiency in alpha-1,6-glucosidase (debranching enzyme) Organ affected -- Muscle and liver Glycogen in the affected organ -- Increased amount; short outer branches *Patients possess glycogen molecules with large number of short branches. Light hypoglycemia and hepatomegaly.

Answer 49

GSD III -- Cori Disease

Question 50

Name the following glycogen storage disease based on the characteristics -- Patients have long chain glycogen with fewer branches Causes enlargement of liver and spleen, scarring of liver tissue (cirrhosis) Death by 5 years of age

Answer 50

GSD IV -- Andersen Disease

Question 51

Name the following glycogen storage disease based on the characteristics -- Deficiency in muscle glycogen phosphorylase Rate limiting step of glycogen breakdown Patients unable to supply muscles with enough glucose Have weakness, muscle cramps Exercise intolerance Myoglobinuria (myoglobin in urine) Tolerance by reducing strenuous exercise

Answer 51

GSD V -- McArdle Disease

Question 52

Name the following glycogen storage disease based on the characteristics -- Deficiency in liver glycogen phosphorylase Prevents glycogen breakdown in liver, hence it accumulates in the liver causing hepatomegaly Low blood glucose levels

Answer 52

GSD VI -- Hers Disease

Question 53

Name the following glycogen storage disease based on the characteristics -- Defect in alpha-glucosidase Causes accumulation of glycogen in lysosomes Disrupts functioning of muscle and liver cells Progressive muscle weakness and myopathy (heart and skeletal) Children die of heart failure

Answer 53

GSD II -- Pompe Disease

Question 54

Enzyme replacement therapy (ERT) for GSD II (Pompe) is done by taking recombinant _________ and delivering it via intravenous infusion in babies/young children. (Myozyme and Lumizyme, Genzyme Corporation -- FDA approved)

Answer 54

alpha-glucosidase