Glucogenolysis Week 2 Flashcards
Weight of glycogen in liver and muscle What are the glycogen reserves used for
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
What is glycogenolysis
The break down of glycogen to glucose or glucose 6-P
When are glycogen levels high? and how long do they last
Highest after eating then slowly decreases.
Glycogen last for 12-24 hours during fasting
What sugar is in glycogen and what bonds does it have?
What organs would you find an what compartment of those organs
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
What is the main difference in glycogenolysis between the liver and every other cell? Dicuss function difference to!
In the liver Glycogen–> Glucose 6-P– GLUCOSE (this is to balance blood gluose)
Every other cell–> Glucose 6-P–> GLYCOLYSIS so gnerates ENERGY
Pattern of Glycogen Content
After breakfast ectra glucose goes to storage so it’s high. Slowly depletes between meals until it is restored.
What enzyme do muscle lack that makes glucose formation possible?
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**
Main differences in red and white muscle fibers
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
Structures of glycogen
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
Why is glucose as glycogen
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
Why is glycogen branched
More sites for degradation and synthessis so the process happens more quickly
The first step in glycogenolysis
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
Difference in glycogen phosphorylase and alpha amylase
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 `
Steps of Glycogenoylsis
- Glycogen phoshoylase phosohorylsis breaking glycosidic bond yeirld Glucose 1-P. This stops 4 units away from a branching point.
- 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)
- 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.
- 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
Explain why we call the branching enzyme bifunctional
- 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)
- 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)
What is McArdle syndrome
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
What Hers disease
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
What is Pompe disease
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
What is Cori’s disease
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.
What is Type 1.Von Gierke’s disease
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
- serious hypoglycemia and the liver can’t make any glucose! Very serious. 2. Enlarged renal, liver because glycogen is accumulating and sitting there.
- Fatty liver- glucose 6-P is accumulating so it goes for fatty acid synthesis (some released and some stuck in liver).
- Lactic acidosis,
- 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
LIst some common myths of ED
- Obestity is the most common ED– false obestiy isn’t an ED
- Ppl are anorexia to look like models
