Glycogen And GSD

Question 1

Where is glycogen stored and which one is responsible for regulating the blood glucose?

Answer 1

Liver and skeletal muscle

- the liver will regulate blood sugar whereas the skeletal muscle will only use the glucose for itself while exercising.

Question 2

What is the product of breakdown in the muscle? Liver?

Answer 2

Muscle - glucose-6-phosphate because skeletal muscle lacks glucose-6-phosphatase. It then enters glycolysis
Liver - glucose, which enters circulation.

Question 3

When will gluconeogenesis be highest? How about glycogenolysis?

Answer 3

Both mirror each other because they are kind of the same process. When you have dietary glucose, so right after eating a meal, these will be decreased. When fasting or if you haven’t eaten in a while these will be increased.

Question 4

What is one reason pertaining. To this lecture. That blocking blood flow to the heart is very bad??

Answer 4

Cardiac muscle has very little glycogen storage so it relies on blood flow to bring it glucose so if there is a blockage the heart will have no glucose and thus no energy.

Question 5

how can we get lactic acidosis?

Answer 5

You get glucose, in this situation through the breakdown of glycogen, and if there is no oxygen, the pyruvate does not enter the TCA cycle but rather turns into lactate

Question 6

Why does lactic acidosis cause hyperuricemia?

Answer 6

There is a transporter, URAT1, that is triggered by Latin acidosis that swaps urate for organic anions (lactate). Thus when we get rid of lactate, we hold onto urate.

Question 7

What is the similarity between glycogen and starch?

Answer 7

Both have predominantly alpha-1,4-linkages and the occasional alpha-1,6-linkage which serve as branch points.

Question 8

What is the difference between glycogen and cellulose?

Answer 8

Glycogen has alpha-1,4-linkage

Cellulose has beta-1,4-linkage

Question 9

What are the steps glycogenesis?

Answer 9

Glucose –> G-6-P (hexokinase in muscle or glucokinase in liver)
G-6-P –> G-1-P (Phosphoglucomutase)
G-1-P –> UDP-Glucose (Glucose 1-phosphate uridyl transferase)
Glycogen Synthase - adds glucose residues by catalyzing the formation of alpha-1,4-linkages.
- glycogen synthase can’t initiate this process though. Rather there is a molecule called “glycogenin” that adds the first 8 glucose molecules before glucagon synthase can get involved.
Branching enzyme - comes in and creates the branches for glycogen synthase to add on to.

Question 10

Glycogenin

Answer 10

Initiates the process of glycogenesis and adds the first 8 residues of so of glucose before glycogen synthase can get involved.

Question 11

Steps in glycogenolysis

Answer 11

Glycogen phosphorylase - cleaves alpha-1,4-glycosidic bonds until there is only 4 residues left on each branch.
Debranching enzyme - shifts three of the remaining 4 residues from one branch to another so that there is only 1 residue left on the branch.
- Debranching enzyme then comes back and removes the final glucose molecule.

Question 12

Glycogen phosphorylase

Answer 12

Responsible for cleaving alpha 1,4 glycosidic linkages until there are only 4 residues left on each branch.

Question 13

Debranching enzyme

Answer 13

1) chops off 3 of the remaining 4 glucose molecules and moves them only a different branch.
2) removes the final glucose molecule.

Question 14

Skeletal muscle can’t deliver glucose to the blood because of. The lack of which enzyme?

Answer 14

Glucose 6 phosphate

Question 15

WHat are some allosteric regulators of glycogen metabolism In the liver?

Answer 15

Liver - ATP, G-6-P, and glucose all cause less glycogen breakdown
- Glucose-6-phosphate will even increase glycogen production

Question 16

What are some examples of allosteric regulation of glycogen metabolism in the muscle?

Answer 16

Muscle - Calcium and AMP will cause increased breakdown of glycogen.

• G-6-P and ATP will cause decreased breakdown of glycogen.
• G-6-P will even cause increase synthesis of glycogen

Question 17

What is the affect of glucagon and epinephrine on glycogen breakdown?

Answer 17

They cause the phosphorylase kinase to be phosphorylated and thus activated. In turn, phosphorylase kinase will phosphorylate glycogen phosphorylase B into A, which activates it.
- glycogen synthase will also be de phosphorylated and inactivated.

Question 18

Phosphorylase kinase

Answer 18

Acted on by epinephrine and glucagon. In these presence of these it will be phosphorylated ad activated. This then phosphorylates glycogen phosphorylase to its active “a” form.

Question 19

Glycogen phosphorylase

Answer 19

Breaks down glycogen into glucose-1-phosphate

Question 20

Pathway of glucagon/epinephrines affect on glycogen

Answer 20

Epi/Glu –> phosphorylase kinase –> glycogen phosphorylase –> breakdown of glycogen into glucose-1-phosphate
–> glycogen synthase is also inactivated

Question 21

Von Gierke Disease

Answer 21

Deficiency of glucose-6-phosphatease

• we can’t complete the breakdown of glycogen and we will be stuck at the last step.
• affects the kidney and liver
• hypoglycemia (makes sense because can’t break down glycogen)
• treat with frequent feeding with carbs, specifically uncooked starch.

Question 22

Pompe’s

Answer 22

Deficiency of alpha-1,4-glucosidase

• this basically means that we can’t degrade the glycogen in the lysosome.
• affects the heart.
• will see accumulation in cardiac tissues, cardiomegaly, LVH and death by ages 2.

Question 23

Cori’s

Answer 23

Defect in Debranching enzyme

• can’t properly break down glycogen, which causes hypoglycemia.
• this causes shorter branches
• it will affect the liver mostly and patient will present with hepatomegaly

Hint: CD - Coris = Debranching

Question 24

Andersons

Answer 24

Defect in branching Enzyme

• no branching, but rather long insoluble chains.
• causes infantile cirrhosis of the liver and hepatomegaly.
• failure to thrive and death

Hint: AB, Andersons = Branching

Question 25

McArdle’s

Answer 25

Defect in glycogen phosphorylase (muscle)
- this will cause there to be an inability to break down glycogen in the muscle. Presents with decreased exercise tolerance with muscle cramps and possible myoglobinuria

Hint: M&M, McArdles = Muscles

Question 26

Her’s

Answer 26

Defect of glycogen phosphorylase (liver)
- glycogen accumulated in the liver and causes hepatomegaly and fasting hypoglycemia.

Hint: Women are less muscular than men, so Her’s defect will be the same but won’t affect the muscles.

Question 27

Tauri’s

Answer 27

Defect in phosphofructokinase (muscle)

- reduced exercise tolerance, myoglobinuria, and HEMOLYTIC ANEMIA.

Question 28

What two organs always need glucose at all times?

Answer 28

Brain and RBCs

Brain will use ketone bodies sometimes

Question 29

Effects of excessive amounts of uncooked starch

Answer 29

Diarrhea
Infection by disease causing organisms
Toxin production
Gas formation
Increase in microbe-mediated formation of carcinogenic compounds