Glycogen Degradation Flashcards
- Understand the structure of glycogen and why relative to stored fatty acids, glucose is the more versatile energy source
Glycogen- highly branched homopolymer of glucose present in all tissues. (contain alpha 1,4 linkages and at every 12th residue, alpha, 1,6 linkages)
compared to FA’s, glucose released from glycogen is readily mobilized and a good source of energy for strenuous activity, supplies energy for anerobic activity (absence of O2) and maintains blood glucose [ ] between meals, supplies brain with glucose.
*Consider the distinction between muscle and liver in terms of glycogen synthesis and degradation (energy needs of each organ) .
a
*Understand what the enzymes; glycogen phosphorylase, transferase and alpha- 1, 6 glucosidase do.
a
- Know what organ and know why this organ has the enzyme, glucose 6-phosphatase.
What makes this enzyme unique?
LIVER has glucose-6- phosphatase, which is an enzyme that generates FREE GLUCOSE from glucose 6-phosphate.
The free glucose is released into blood for use by other tissues such as brain and red blood cells.
Glucose6-phosphatase is ABSENT in most other tissues (unique)
(glucose 6-phosphate uses H2O to form free glucose).
*Understand the regulation of glycogen phosphorylase in liver vs muscle.
Liver glycogen phosphorylase- default state is A form (insensitive to AMP). Normally in R state
Allosterically regulated by glucose, as binding phosphorylase to glucose, will convert R to T state
Muscle glycogen phosphorylase- default state is B form (normally in T state) . muscle uses glucose especially during exercise.
Where are the largest stores of glycogen in the cells?
in liver and skeletal muscle.
How are glycogen stores utilized in liver compared to muscle cells?
The LIVER breaks down glycogen and releases glucose to blood to provide energy for brain and red blood cells during nocturnal fasts
MUSCLE glycogen stores are mobilized to provide energy for muscle contraction (selfish)
Describe the different parts of glycogen granule or molecule. What process takes place at the core of glycogen?
The glycogen molecule has nonreducing ends that form surface of glycogen;
Core of glycogen molecule is the protein glycogenin, which is the site where glycogen degradation takes place.
What makes the alpha 1,6 bonds special in glycogen?
alpha 1,6 glycosidic bonds cannot be cleaved by glycogen.
What enzyme converts Glucose-1-phosphate into glucose-6-phosphate?
What intermediate is used to get product (G-6P)?
PHOSPHOGLUCOMUTASE. This enzyme will use 1,6 bisphosphate intermediate to convert G-1P to G-6P
How does glycogen phosphorylase help produce glucose 1-phosphate? What makes this reaction energetically advantageous?
Glycogen phosphorylase degrades glycogen form nonreducing ends of glycogen molecule.
phosphorylase will catalyze phosphorolysis reactions that yields glucose-1-phosphate.
Reaction energetically advantageous, because released sugar is already phosphorylated, do not need to use ATP for phosphorylation.
Also, in muscles, there are no transporters that exist for glucose-1-phosphate.
what are the three enzymes that are required for enzyme breakdown?
- Glycogen phosphorylase- cannot cleave near branch points and can only cleave alpha 1,4 glycosidic bonds
- Transferase- shifts a small oligosaccharide near the branch point to a nearby chain, making glucose moieties accessible to phosphorylase.
- Debranching enzyme (alpha-1,6 glucosidase)- then cleaves the alpha-1,6 bond at branch point, releasing a free glucose.
free glucose then phosphorylated by hexokinase to produce glucose-6-phosphate.
Which of the three enzymes in glycogen breakdown are Michaelis Menten?
Transferase and glucosidase are michaelis menten enzymes.
What is liver’s main role regarding glucose?
Liver’s role is to maintain a nearly constant concentration of glucose in the blood.
What is the key regulatory enzyme for glycogen degradation? How many forms exist of this enzyme and how do they differ? What kind of equilibrium state does each form favored (relaxed or tense state)
The key regulatory enzyme is GLYCOGEN PHOSPHORYLASE.
The phosphorylase exists in two forms, a LESS active form B and MORE Active form a.
A form - a serine reside is phosphorylated.
B form- no phosphorylated serine form.
Both a and b form display R T equilibrium (T- relaxed T- tense)
In A form, the R (relaxed) state is favored
In B form, the T (Tense) state is favored.
What is the equilibrium state for Liver Phosphorylase?
What is a negative regulator of liver phosphorylase and why?
Liver phosphorylase is in the A form (phosphorylated serine) in R state.
Liver phosphorylase is prepared to generate blood glucose unless signaled otherwise.
GLUCOSE is a negative regulator of liver phosphorylase, that will lead to transition of R state to T state.
If there are high levels of glucose, the phosphorylase enzyme will shut down.
Differentiate between the T and R state structurally. Also describe the difference in phosphorylation level in liver and muscle.
In the T state, the active site is partly BLOCKED by regulatory structure.
In R state- active site NOT obstructed.
In liver, there is LARGE phosphorylation, occurs most of the time.
In the muscle, there is NO phosphorylation until hormone induces signal transduction.
Differentiate between the T and R state structurally. Also describe the difference in phosphorylation level in liver and muscle. Which state is more active?
In the T state, the active site is partly BLOCKED by regulatory structure.
In R state- active site NOT obstructed.
In liver, there is LARGE phosphorylation, occurs most of the time.
In the muscle, there is NO phosphorylation until hormone induces signal transduction.
The R state is more active.
What is the default form of phosphorylase in muscle? What is equilibrium state is muscle usually in? What must occur before muscle switches to R state?
What are the two things its phosphorylase is stabilized by?
In muscle, default form is phosphorylase B, in T state.
When energy change is needed, signaled by increase in concentration of AMP, the phosphorylase will bind AMP and stabilize R state.
The T state of phosphorylase b is stabilized by ATP and Glucose-6-phosphate.
Describe phosphorylase a in terms of activation. What pushes its activation? What factors is this phosphorylase a not sensitive to?
compare this level of activation and phosphorylation to phosphorylase b? What makes it switch from b to a?
Phosphorylase A is fully active.
Phosphorylation pushes it to be fully active.
It is not sensitive to AMP, ATP, and glucose-6-phosphate (seen in LIVER)
Phosphorylase B is mostly INACTIVE and NOT phosphorylated (in MUSCLE).
The AMP levels push it to R state, as increasing energy demands will activate signal transductions pathways to phosphorylate b and allow it to become a.
What happens to equilibrium state when there is a lot of ATP? a lot of AMP?
A lot of ATP, the more favored form is T state.
A lot of AMP, more favored form is R state
What process converts the promotion of Phosphorylase b to phosphorylase a? How does a form differ from b.
What hormones stimulate phosphorylation and what is the result of phosphorylation.
PHOSPHORYLATION promotes conversion of phosphorylase b to a.
A form- Serine residue 14 is phosphorylated.
B form- not phosphorylated.
Phosphorylation is stimulated by hormones GLUCAGON and EPINEPHRINE (adrenaline)
Phosphorylation alters the active site such that Alpha-helices that partly block the active site in b, are removed.
What enzyme is responsible for converting glycogen phosphorylation from unphosphorylated b form to a form?
How is this enzyme activated? How is Phosphorylase kinase activated and when is it most active?
PHOSPHORLASE KINASE - enzyme that converts Glycogen phosphorylase from b form (unphosphorylated) to a form
This enzyme is activated by both PHOSPHORYLATION and CALCIUM binding.
Phosphorylase kinase is phosphorylated by PROTEIN KINASE A.
The Delta subunit of phosphorylase kinase is the calcium sensor CALMODULIN.
Phosphorylase kinase is most active when phosphorylated and bound to calcium.
Differentiate between the three muscle fiber types and what processes are used for gaining ATP.
Muscles are composed of several muscle fiber types:
- Type I- SLOW twitch fibers rely primarily on Cellular Respiration, as means of getting ATP
- Type II b (type IIx) or FAST twitch fibers rely permanently on LACTIC ACID fermentation for ATP generation. Type II b fibers are rich in GLYCOGEN PHOSPHORYLASE
- Type II a fibers- have biochemical characteristics intermediate between other fiber types.
