Glucogenolysis Week 2

Question 1

Weight of glycogen in liver and muscle What are the glycogen reserves used for

Answer 1

10% of liver (maintain blood glucose) 1-2% of muscles (fuel reserve for ATP synthesis) Although since muscle is has a greater overall weight it has 2x the amount of glycogen

Question 2

What is glycogenolysis

Answer 2

The break down of glycogen to glucose or glucose 6-P

Question 3

When are glycogen levels high? and how long do they last

Answer 3

Highest after eating then slowly decreases.

Glycogen last for 12-24 hours during fasting

Question 4

What sugar is in glycogen and what bonds does it have?

What organs would you find an what compartment of those organs

Answer 4

Only glucose and alpha 1-4 and alpha 1-6 (so glycogen is branched)

Found in large amounts liver and muscle and most cells have some sort of glycogen in the cytosol

Question 5

What is the main difference in glycogenolysis between the liver and every other cell? Dicuss function difference to!

Answer 5

In the liver Glycogen–> Glucose 6-P– GLUCOSE (this is to balance blood gluose)

Every other cell–> Glucose 6-P–> GLYCOLYSIS so gnerates ENERGY

Question 6

Pattern of Glycogen Content

Answer 6

After breakfast ectra glucose goes to storage so it’s high. Slowly depletes between meals until it is restored.

Question 10

What enzyme do muscle lack that makes glucose formation possible?

Answer 10

Muscle lacks glucose 6-phosphatase the enzyme that takes Glucose 6-p to glucose so most enter glycolysis

** abouit 8% is converted to gree glucose**

Question 11

Main differences in red and white muscle fibers

Answer 11

Red muscles have good blood flow, myoglobin and PACKED with mitochondria. Glycogen to G-6-P– Pyruvate –> CO2 and H2O (36 ATP because muscle use the glycerophophate shuttle)

White has poor blood supply, few mitochondria so the end product is lactate and have an enormous capability to glycogenolysis and glycolysis but only have short term full term capacity

Question 12

Structures of glycogen

Answer 12

Mainly linked by 1-4 glycosidic which in linear and branches 1-6 glycosidic linkage

Branches occur every fourth glucosyl residue within the central cour and even less frequently further out

One starting point (reducing end/active) and we add glucose away towards non reducing ends

Question 13

Why is glucose as glycogen

Answer 13

Energy could be stored as adipose but that isn’t mobilized as fast, can’t be converted without oxygen and can’t maintain glucose levels

Can’t be stored as glucose because that is osmotically active and ATP would have to be used agaisnt the glucose gradient. glycogen doesn’t change osmolarity but glucose does

Question 14

Why is glycogen branched

Answer 14

More sites for degradation and synthessis so the process happens more quickly

Question 15

The first step in glycogenolysis

Answer 15

Glycogen phophosorlysis by glycogen phosphrylase (Pi is cleaved off the amylose chain) taking off one glucose at a time

Glycogen phosphoylase doesn’t need ATP energy to attack the glycosidic bond and to phosphorylase glucose unit which is very advantage because we use use this reserve when cellular energy is low

Question 16

Difference in glycogen phosphorylase and alpha amylase

Answer 16

Both can cleave the glycosidic bond of glycogen chain.

Glycogen phosphorylase does so by releasing phosphorylase without energy, while the alpha amylase attacks the amylase chain by hydrolysis so it using H2O to cleave the bond so it’s a non phosphorylated glucose `

Question 17

Steps of Glycogenoylsis

Answer 17

1. Glycogen phoshoylase phosohorylsis breaking glycosidic bond yeirld Glucose 1-P. This stops 4 units away from a branching point.
2. glucose 1-P isn’t ready to be used so phosphoglucomutase attacks making it Glucose-6-P (which is a juntion point of either aerobis or anoerobic)
3. The liver has glucose 6-phosphatase which can produce glucose

3B. In cells where this enzyme doesn’t exist (or there isn’t the translocase to move the GP6 into the ER) there is Type 1 glycogen storage. Periperal tissues use glycolysis producing either lactate or oxidation making CO2.

4. Debranching enzyme- bifcuntioanl and 1st is transferase and moves a strand of 3 glocosyl residue from a 4 branch and transfer it to a free hydroxyl group of the same or adjacent glycogen molecle making the amylose chain longer

Question 18

Explain why we call the branching enzyme bifunctional

Answer 18

1. It is a transferase- transfer 3 of the 4 gluocse units to a non reducing end of an amylose chain (where the glycogen phosphorylase can handle it)
2. Glucoidase- cleaves the 1-6 glycosidc bond at the branching point making FREE GLUCOSE (remember that most glycogen degradation makes glucose phosphate but at a branch a point we make glucose– this is good for the liver because it can immediately can be pushed out to the circulation; it also would need to be phosphorylated to enter the glycolitic pathway)

Question 19

What is McArdle syndrome

Answer 19

AKA type 5 is Complete loss of skeletal **muscle phosphorylase (so the first step in glycogen degradation to make Glucose 1-P can’t ever happen) **. You can store glycogen but never use it.

McArdle patient’s suffer from painful cramps and cant preform strenuous exercise. They don’t have the normal lactate build up due to exercise but the muscles are often damaged due to excess glycogen accumulation and low energy supply.

they can use creatine phosphate for quick 1 ATP energy

CNS is normal because they use glucose and don’t need gylcogen breakdown

Increae in myoglobin in the blood and urine– when cells aren’t getting enough energy they lyse and go in circulation

Question 20

What Hers disease

Answer 20

AKA Type VI is deficiency in LIvers phosphorylase isn’t there, so you may have hypoglycemia during fasting. Normally glycogen is the first source to supply energy levels but other than hypoglycemia during fasting patients can be normal

Question 21

What is Pompe disease

Answer 21

TypeII glycogen disease is a lysosomal storage disease due to deficiency in Lysosomal 1–>4 glucosidase deficieiny. Glycogen accumulates in lysosome and it kills the cell. Can lead to cardiomegally is one of the first signs because so nothing can be degraded so build up

Question 22

What is Cori’s disease

Answer 22

Type III- the debrancher deficiency. So you can taper down the peripheral amylose chain until 4 glucose units away from branch point so you get some Glucose 6-p, but you’re building this huge gylcogen molecule and you don’t use it all. You can get Mild fasting hypoglycemia.

Question 23

What is Type 1.Von Gierke’s disease

Answer 23

two subtypes- but both have deficiency with the gluocse 6-phosphatase and affect only the liver and kidney (remember that the other cells go from Glucose 6-P to glycosolysis and odn’t need to be broken down to glucose)

1A. Missing the G-6 phosphatase enzyme- this is the last step in the liver that removes the phosphate and makes free glucosen (most frequen)

1B. Missin translocase enzyme- enzyme that takes G6P from the cytosol to the ER for phosphatase attack through Glut 7

1. serious hypoglycemia and the liver can’t make any glucose! Very serious. 2. Enlarged renal, liver because glycogen is accumulating and sitting there.
2. Fatty liver- glucose 6-P is accumulating so it goes for fatty acid synthesis (some released and some stuck in liver).
3. Lactic acidosis,
4. can cause gout (through hyperuricema- push into the pentose pathway so more uric acid)

These patients should ALWAYS eat carbs/glucose. Even overnight through a tube

Question 24

LIst some common myths of ED

Answer 24

1. Obestity is the most common ED– false obestiy isn’t an ED
2. Ppl are anorexia to look like models

Question 25

Common non-myths

Answer 25

1. ED carry the highest mortality rate of mental illness
2. Anorxia is closely related to birth order (youngest most likely)
3. Vegetarinism is an early marker of ED

Question 26

Peak populations in ED

Answer 26

Young adolescent girls and young womrn

Greater in white and asians

Two peak ages transitional 13-14 and 17-18 years

Only 5-10% in males

But remember ED are equal opportunity illness

Question 27

Weight ranges in ED

Answer 27

Anorexia-nervosa- under weight (restrictive type and binge eating/purging)

Buliminia Nervosa- average weight

Binge eating- overwieght

Question 28

Charateristics of anorecia

Answer 28

1. refusal to gain weight
2. Fear of gaining weight
3. Disturbance in the way ones body is experienced
4. Amerorhhea (removed from recent DSM)

Question 29

Characteristics of bulminia nervosa

Answer 29

1. Binge eating
2. COmpensatory purging
3. binge/purge at least 2x/week
4. Negatice self evaluation
5. Not during episodes of anerxia nervosa (cant be under weight)

Question 30

Compensatory Behaviors in Bulimia nervosa

Answer 30

1. Self induced vomitting
2. MIsuse of laxatives, diuretics, enemas (metabolic stimulants)
3. Fasting
4. Extreme excerise
5. Diabetics failutre to take insulin

Question 31

Why is ED an ethical dilemma

Answer 31

Its a emntal disorder with the highest mortality often due to medical complications, but weight loss is universal sign of illness

Question 32

Obstacles to early disorder

Answer 32

1. Patients fear
2. Patients hide it
3. Confidentiality hinder flow of info
4. Symptoms are hidden as other illnesses
5. Mistaken notion that patients dont want help

Question 33

Good questions to ask nin ED

Answer 33

1. How much do you want to weight
2. you or anyone concerns with your weight
3. Weight control methods

Question 34

Difference in body weight assestment in bulimina and anerxia

Answer 34

Anorexia- under eweight and can’t gain or maintain

Bulimia- extreme fluctutions but usually in normal

Question 35

five components of Detection to ED

Answer 35

1. History and physical
2. Interview friends and family
3. CMP
4. Self/family report instruemtns (EAT-26(
5. Follow up

Question 36

Two key components in treating

Answer 36

1. ED are more about weight than eating
2. Body weight is key to understanding and treating

Question 37

treatment at RUsh discussed.

Answer 37

phaes !- inpatient

Phase II- outpaitent meal an weight monitored by family

Phase III- outpatient follow up

Let patietn develip own meal plan (you pick portions)

gradually increase meal quota

Hold patients accountable (circle failed meals in red, bed rest, naso-gastric when needed)

Question 38

Common myth about how patients see themselves

Answer 38

Most patients see themselves as their actual size but affective (feel) and cognitive (think) they are too fat or fat

Question 39

Which patients need the greatest calroies to gain weight

Answer 39

THINNIEST! Because SA/Weight= calories so they need the most to gain but maintaining declines.