Flashcards in Lecture 6 - Glycogen Structure, Regulation of Glucogen Metabolism Deck (50):
A desirable characteristic of a storage form of glucose is that glucose can be easily deposited in the well-fed state and easily mobilized during fasting. Why is the highly branched structure of glycogen responsible for this property?
Both synthesis and degradation occur at the end of branch points, also known as the non-reducing ends
During what "state" does the liver store glycogen?
During what "state" does the liver degrade glycogen to provide glucose?
When is glycogen degraded in the muscles?
during exercise (muscle glycogen does NOT contribute to blood glucose in the fasted state)
The net energy cost of incorporating each free glucose molecule into glycogen is:
2 high-energy phosphate bonds
What is the frequency of branching in glycogen?
every 8-10 glucose units
The glucose monomers within a chain are held together by ______________ bonds.
a-1,4 glycosidic bonds
The branch points in glycogen are created by ______________ bonds.
a-1,6 glycosidic bonds
"Trapping the glucose" inside the cell is the initial step in converting blood glucose to glycogen. a) How is this achieved, and b) what enzymes are used?
a) Phosphate group transferred from ATP to the C6 hydroxyl group of glucose
b) Catalyzed by tissue-specific isozymes, hexokinase, and glucokinase
How does insulin aid in trapping the blood glucose in the plasma membrane?
GLUT-4 transporter is recruited to plasma membrane by insulin, making more intracellular glucose available
How does insulin impact glucose uptake in the liver?
Insulin induces the synthesis of glucokinase, ensuring continued uptake of glucose in the liver
What enzyme catalyzes the conversion of Glucose-6-P to Glucose-1-P?
In order for Glucose-6-P to be stored as glycogen, it must first be converted to:
An essential intermediate in the conversion of glucose-6-P to glucose-1-P is:
What are mutases?
Enzymes that move a group from one position to another within the same molecule
Substrates in the formation of UDP-Glucose are Glu-1-P and UTP. What enzyme catalyzes this reaction?
Glycogen synthase catalyzes the transfer of glucose from UDP-glu to _________.
A non-reducing end of the glycogen fragment
The transfer of glucose from UDP-glu to a non-reducing end of the glycogen fragment results in the formation of:
an a-1,4-glycoside bond
In the absence of a glycogen primer, what acts as an acceptor of the initial glucose residue in the transfer of glucose from UDP-glu to the glycogen fragment?
the protein glycogenin
What are 3 consequences of branching?
1. increased solubility
2. increased number of non-reducing ends
3. increased potential for rapid mobilization and deposition of glucose
How does insulin promote fuel storage?
Insulin promotes the dephosphorylation of key enzymes involved in glycogen metabolism.
What two molecules are antagonists of the effects of insulin?
Promotion of fuel storage by insulin is medicated by what two mechanisms?
1. Insulin activates protein phosphastase
2. Insulin results in decreased levels of cAMP
Both glucagon and epinephrine _______ levels of cAMP in the cell
In the fed state, what happens to the insulin/glucagon ratio?
It increases - meaning levels of insulin activate protein phosphastase 1 and glycogen synthase is active.
In the fasted state, what happens to the insulin/glucagon ratio?
It decreases, meaning cAMP levels are increased, and glucagon/cAMP activate Protein Kinase A.
What effect does phosphorylation have on glycogen synthase activity?
Phosphorylation inactivates glycogen synthase
A low insulin/glucagon ratio promotes:
phosphorylation of glycogen synthase
_________ is activated by a high insulin/glucagon ratio.
protein phosphastase 1
What effect does glucose-6-P have on glycogen synthase?
High concentrates of G-6-P will allosterically activate the normally inactive phospho-form of glycogen synthase.
When G-6-P accumulates in the cell faster than it is being used by catabolic pathways, it allosterically activates phospho-glycogen synthase. What else does G-6-P activate?
Which of the following is NOT a condition promoting glycogen mobilization?
A. degradation in between meals to maintain constant blood glucose levels
B. An increase in glucagon
C. An increase in epinephrine
D. An increase in the insulin/glucagon ratio
E. An accumulation of AMP in muscle
D - A decrease in the insulin/glucagon ratio (i.e. an increase in glucagon) promotes glycogen mobilization.
____________ catalyzes the rate-limiting step in glycogenolysis.
A cofactor is required to form a Schiff's base with a lysyl E-amino group at the active site of glycogen phosphorylase. What is this cofactor?
Pyridoxal-phosphate (vitamin B6)
What is the function of Glucan transferase during the debranching of glycogen?
cleaves one a-1,4 glycosidic bond and forms another, creating a longer chain that is a better substrate for phosphorylase
Glycogen phosphorylase releases Glu-1-P. In contrast, the a-1,6 glucosidase reaction __________.
releases free glucose
What is an important allosteric activator in skeletal muscle and acts as an indicator of the decreased energy status of the cell?
What is an important allosteric inhibitor in the liver isozyme and indicates the glucose status of the cell?
Binding of epinephrine to _____________ receptors increases cAMP levels in the muscle cell.
What happens to cAMP levels in the muscle cell when epinephrine binds to B-adrenergic receptors?
cAMP levels increase increase in muscle cell
What effect does epinephrine binding to a-epinephrine receptors have in the muscle cell?
Ca2+ concentration increases in muscle cell
_______ allosterically activates phosphorylase kinase to synchronize muscle contraction with glycogenolysis.
Under conditions of atoxia and ATP depletion, what effect will AMP have in the muscle?
Accumulation of AMP will allosterically activate the inactive dephospho-form of glycogen phosphorylase.
Epinephrine can bind to B-adrenergic receptors in the liver, involving a cAMP-dependent cascade which activates protein kinases. What mediates hormonal activation by epinephrine binding to a1-receptors?
second messengers inositol triphosphate (IP3) and Ca2+
What are 3 allosteric inhibitors of glycogen phosphorylase?
What is the GL protein?
regulatory subunit that directs PP1 to glycogen phosphorylase (for dephosphorylation)
What two molecules inhibit the interaction of PP1 and GL?
Synthesis of cAMP is stimulated by what two molecules?
1. epinephrine in liver/muscle
2. glucagon in liver
Degradation of cAMP Phosphodiesterase is activated by insulin. What is it inhibited by?