Glycogen Metabolism. Flashcards
1
Q
What is glycogenolysis?
A
The breakdown of glycogen to form glucose.
2
Q
What is UDP glucose?
A
A high energy molecule formed that can donate glucose residues to a growing glycogen chain.
3
Q
What kind of molecule is glycogen?
A
A storage polysaccharide.
4
Q
What is the monomer that is used to form glycogen?
A
Glucose.
5
Q
What kind of structure does glycogen have?
A
It is a highly branched molecule.
6
Q
Why is glycogen branched?
A
So each branch can be broken down at the same time, releasing multiple glucose residues.
7
Q
Will glycogen be broken down in the well fed state or the fasting state?
A
In the fasting state.
8
Q
Will glycogen be formed in the well fed state or the fasting state?
A
In the well fed state.
9
Q
Why is glycogen broken down?
A
So that blood glucose levels can be maintained in the fasting state.
10
Q
What is the process called when glycogen is made?
A
Glycogenesis.
11
Q
What is the process called when glycogen is broken down?
A
Glycogenolysis.
12
Q
Where in the cell are glycogen molecules stored?
A
In the cytoplasm.
13
Q
How is glycogen stored in the cytoplasm?
A
In granules that are closely associated with the enzymes that synthesise and degrade glycogen.
14
Q
Which kind of cells have the highest concentration of glycogen?
A
Muscle cells.
Liver cells.
15
Q
What is liver glycogen mainly used for?
A
To maintain blood glucose levels in the fasting state.
16
Q
Does glycogenolysis occur at the same time as gluconeogenesis?
A
No.
Gluconeogenesis takes a long time to get going so glycogenolysis will maintain blood glucose levels until gluconeogenesis gets going.
17
Q
What condition will liver glycogen prevent?
A
Hypoglycaemia.
18
Q
What is muscle glycogen primarily used for?
A
It is used to produce ATP so that it can be used as energy during exercise.
19
Q
How is muscle glycogen used in the fight or flight state?
A
Glycogen is used to produce energy for running or fighting in life threatening situations.
20
Q
What percentage of muscle weight is glycogen?
A
2%.
21
Q
Does liver glycogen levels remain constant throughout the day?
A
No, they fluctuate.
22
Q
How does liver glycogen levels fluctuate throughout the day?
A
They tend to be highest after a meal and then decrease until another meal is consumed or they run out.
23
Q
When are glycogen levels at their lowest in a normal day?
A
Before breakfast.
24
Q
Are muscle glycogen levels affected by short fasts?
A
No.
25
What will mainly deplete muscle glycogen levels?
Exercise.
26
Why is muscle glycogen used during exercise?
Because extra energy is needed so glycogen is broken down to ATP.
27
Will muscle glycogen be affected by any fasts?
Only by very long fasts that last for weeks.
28
Is some glycogen always preserved in muscles during long fasts?
Yes.
It is preserved for fight or flight situations.
29
What kind of molecule is glycogen?
A branched chain homo-polysaccharide.
30
What kind of glucose molecules make up glycogen?
α-D-glucose subunits.
31
What bonds are link the glucose residues in the straight chains of glycogen?
α-1,4 glycosidic linkages.
32
What bonds are link the glycogen branches to the straight chains of glycogen?
α-1,6 glycosidic linkages.
33
How often is there a branch in a glycogen chain?
Every 8-10 glucose residues.
34
Do glycogen branches occur more frequently in the centre or periphery of a glycogen molecule?
In the centre.
35
What is the anomeric carbon in a glycogen molecule attached to?
To a protein called glycogenin.
36
What links the anomeric carbon to glycogenin?
A glycosidic bond.
37
What end of the glycogen molecule will the anomeric carbon be on?
The reducing end.
38
What ends are the terminal glucose residues on the glycogen molecule called?
The non reducing ends.
39
Are there many reducing ends on a glycogen molecule?
No.
There is only 1 reducing end on a glycogen molecule.
40
Are there many non reducing ends on a glycogen molecule?
Yes.
Each terminal glucose residue on each chain or branch is a non reducing end.
41
What ends of glycogen molecules are glucose residues added to or removed from?
The non-reducing ends.
42
What molecule is used to store glucose in plants?
Amylopectin.
43
How does amylopectin differ from glycogen?
Amylopectin has less branches than glycogen.
44
How many residues will be between branches in an amylopectin molecule?
Every 20-30 glucose residues.
45
Why is glycogen branched?
So that there are many non reducing ends that can be worked on at the same time.
46
What is the advantage of allowing multiple enzymes to work on multiple branches of glycogen at the same time?
It takes less time to release the stored glucose.
47
Can multiple enzymes add multiple glucose residues to the multiple non reducing ends?
Yes.
48
How does branching affect the solubility of a molecule?
Branching increases the solubility of a molecule.
49
What 3 factors make glycogen a better rapid energy source than fat?
Glycogen can be broken down anaerobically.
Glycogen can be broken down very quickly.
Glycogen breakdown does not require energy.
Glycogen breakdown forms glucose which can be used for energy bu the brain.
50
Why is it important for the muscles to break down glycogen quickly?
Because energy is needed quickly in fight or flight situations.
51
Why is it important that glycogen can be broken down anaerobically?
Because strenuous exercise creates anaerobic conditions.
52
Can fat be broken down anaerobically?
No.
53
Does the breakdown of glycogen require any energy?
No.
54
Does the beta oxidation of fat require any energy?
Yes.
55
Can the brain use fatty acids as an energy source?
No.
56
What is the body's primary energy source for fight or flight situations?
Glycogen stores.
57
Is glycogen synthesis anabolic or catabolic?
Anabolic as a large molecule is built up from smaller pre-cursors.
58
Is glycogen synthesised in the well fed or in the fasting state?
In the well fed state.
59
What must be present for glycogen to be synthesised?
A primer.
60
What 2 molecules can make up a glycogen primer?
A glycogenin protein.
A pre-formed glycogen molecule.
61
When will glycogen be used as a glycogen primer?
When glycogen molecules are still available as they haven't been broken down.
62
When will glycogenin be used a glycogen primer?
When glycogen stores have been completely broken down and it needs to be synthesised from new.
63
What happens in step 1 of glycogen synthesis?
Glucose 6-phosphate is converted to glucose 1-phosphate.
64
What enzyme is involved in step 1 of glycogen synthesis where glucose 1-phosphate is formed?
Phosphoglucomutase.
65
What energy is required to form glucose 1-phosphate from glucose 6-phosphate?
None.
66
What happens in step 2 of glycogen synthesis?
UTP is broken into UDP and the the single phosphate group is added to glucose 1-P to form UDP glucose and a PPi.
67
What happens to the PPi group once UDP glucose has been formed in step 2 of glycogen synthesis?
PPi is cleaved to form 2 free, inorganic phosphate molecules.
68
Does the cleavage of PPi in step 2 of glycogen generate any energy?
Yes.
The energy from this reaction is sufficient to drive the remaining reactions forward.
69
What enzyme adds the phosphate group from UTP to glucose 1-phosphate?
UDP-glucose-pyrophosphorylase.
70
What enzyme cleaves the PPi group in step 2 of glycogen synthesis?
Pyrophosphatase.
71
What provides the energy in step 2 of glycogen synthesis?
UTP.
72
What happens in step 3 of glycogen synthesis?
Glycogenin can add UDP glucose onto itself.
Once the 8 UDP glucose residues have been attached to glycogenin, the molecule becomes known as primed glycogenin.
73
Is glycogenin an enzyme?
Yes.
74
Why is glycogenin said to be self-glucosylating?
Because it adds UDP glucose to itself.
75
What are the UDP glucose molecules attached to on a glycogenin molecule?
A tyrosine residue.
76
How many UDP glucose molecules can glycogenin add to itself?
Around 8.
77
What is primed glycogenin?
It is glycogenin that is bound to 8 glucose residues.
78
Is the UDP removed from the glucose residues when they are added to glycogenin?
Yes.
79
What happens in step 4 of glycogen synthesis?
An enzyme called adds UDP glucose residues to the non-reducing end primed glycogenin.
80
When will primed glycogenin be called glycogen?
When the molecule is long enough to form a branch.
81
What happens to the UDP molecules once they are removed from UDP glucose?
The UDP will be converted back to UTP.
82
What enzyme adds glucose residues to glycogen?
Glycogen synthase.
83
What end of glycogen will glycogen synthase add the glucose residues too?
The non-reducing ends.
84
What happens in step 5 of glycogen synthesis?
When glycogen is formed, a branching enzyme will cleave glucose residues from the chain. The cleaved residues are moved 3 residues back along the original chain and then added to form a branch.
85
How many glucose residues are cleaved from glycogen by the branching enzyme?
Around 7.
86
What activity does the branching enzyme have?
Glucosyl α-4-6 transferase activity.
87
What bond is used to form a branch in glycogen?
An α-1-6 glycosidic bond.
88
What happens once a branch has been formed in glycogen synthesis?
Glycogen synthase can add more glucose residues to the non-reducing ends of the branch and to the original chain until another branch can be formed.
89
What happens in step 6 of glycogen synthesis?
UDP glucose is converted back to UTP.
90
Is any energy used to convert UDP back to UTP?
1 ATP.
91
What enzyme converts UDP to UTP?
Nucleoside diphosphate kinase.
92
Is glycogenolysis a catabolic or anabolic process?
Catabolic.
93
What is glucose homeostasis?
The balance of blood glucose levels.
94
How is glucose homeostasis achieved when a person is in the fasting state?
By glycogenolysis and then gluconeogenesis.
95
What are the 5 phases of glucose homeostasis?
The absorptive phase.
The post-absorptive phase.
Early starvation.
Intermediate starvation.
Prolonged starvation.
96
What happens in the absorptive phase?
Exogenous glucose is absorbed from the diet and is used to maintain blood glucose levels and to form ATP.
97
When does the absorptive phase occur?
After a meal.
98
How long will exogenous glucose maintain blood glucose levels for?
Around 4 hours.
99
When does the post absorptive phase occur?
Around 4 hours after a meal when no more glucose can be obtained from the diet.
100
What happens in the post absorptive phase?
Because gluconeogenesis takes a long time start, glycogen stores are broken down and slowly depleted.
101
What is the primary source of glucose in the post absorptive phase?
Glycogen stores.
102
How long do glycogen stores last for?
Around 12 hours.
103
When does the early starvation phase take place?
Around 16 hours after a meal.
104
How long after a meal will the early starvation phase last for?
Around 24 hours.
105
What is the main source of glucose in the early starvation phase?
Gluconeogenesis.
106
When does the intermediate starvation phase take place?
1 day after a meal.
107
When does the prolonged starvation phase take place?
24 days after a meal.
108
How long does the intermediate starvation phase last for?
Upto 24 days after a meal.
109
How long does the prolonged starvation phase last for?
Upto 40 days or until death.
110
What is the primary glucose source in intermediate and prolonged starvation?
Gluconeogenesis. to maintain blood glucose levels. However, aAt this stage, the body is breaking itself down to prevent hypoglycaemia.
111
Will blood glucose levels ever drop during starvation?
After 4 days, blood glucose levels will drop to the minimum amount to prevent hypoglycaemia.
112
What 3 enzymes are used to break down glycogen?
Glycogen phosphorylase.
Glucosyl α-4,4 transferase.
Glucosyl α-1,6 glucosidase.
113
What is the rate limiting step of glycogenolysis?
Step 1.
When glucose residues are cleaved from glycogen.
114
What happens in step 1 of glycogenolysis?
The glucose residues are cleaved from glycogen and are converted to glucose 1-phosphate.
115
What enzyme is used to cleave glucose residues from glycogen?
Glycogen phosphorylase.
116
Does glycogen phosphorylase use any coenzymes?
Yes, pyridoxal phosphorylase.
117
What end will glycogen phosphorylase cleave glucose residues from?
The non reducing ends.
118
Can the glucose residues from multiple non reducing ends be cleaved at the same time?
Yes.
119
When will glycogenolysis stop?
When a branch is around 4 residues long or a chain is around 4 residues away from a branch.
120
What is limit dextrin?
When the branches and chains of glycogen are reduced to 4 residues long and glycogen phosphorylase can no longer cleave them.
121
Can glycogen phosphorylase cleave the glucose residues on limit dextrin?
No.
122
What happens in step 2 of glycogenolysis?
A bifunctional de-branching enzyme will remove 3 of the 4 glucose residues from the branch and add them to the glucose chain.
The same enzyme will then cleave the remaining glucose subunit.
123
What activities does the bi-functional de branching enzymes have?
Glucosyl α-4,4 transferase activity.
Glucosyl α-1,6 glucosidase activity.
124
What activity does the de-branching enzyme use to remove the 3 glucose residues from limit dextrin?
Glucosyl α-4,4 transferase.
125
What is the single glucose residue that is cleaved by the de-branching enzyme released as?
Free glucose.
126
When is the only time in glycogenolysis that free glucose is released?
When the de-branching enzyme uses its glucosyl α-1,6 glucosidase activity to cleave the single glucose residue from a branch.
127
What happens when the 3 glucose residues from limit dextrin are added to the glycogen chain?
They can be cleaved by glycogen phosphorylase until limit dextrin is reached.
128
What activity of the de-branching enzyme is used to cleave the single glucose residue from a branch?
Glucosyl α-1,6 glucosidase activity.
129
What happens in step 3 of glycogenolysis?
Glucose 1-phosphate is cleaved from glycogen and can be converted in the cytoplasm to glucose 6-phosphate.
Glucose 6-phosphate is then carried to the ER of the liver where is is converted to glucose and released into the bloodstream.
130
What enzyme converts glucose 1-phosphate to glucose 6-phosphate?
Phosphoglucomutase.
131
What enzyme carries glucose 6-phosphate to the ER of the liver?
Glucose 6-phosphate translocase.
132
What enzyme converts glucose 6-phosphate to glucose?
Glucose 6-phosphatase.
133
Will glucose 6-phosphatase be found in the ER of all cells?
No.
Only in the ER of liver cells.
134
What happens to the glucose 6-phosphate that is made from glycogenolysis in the muscles?
It will enter glycolysis as it cannot be converted to glucose.
135
Is glucose 6-phosphatase found in muscle cells?
No.
136
What enzymes convert glucose 1-phosphate to glucose in the liver?
Phosphoglucomutase.
Glucose 6-phosphate translocase.
Glucose 6-phosphatase.
137
Is any glycogen stored in the lysosomes?
A small amount of glycogen is stored in the lysosomes.
138
What enzyme breaks down glycogen in the lysosomes?
α-1,6 glucosidase (acid maltase).
139
What are the enzymes that need to be regulated in glycogen metabolism?
Glycogen synthase and glycogen phosphorylase.
140
Why do glycogen synthase and glycogen phosphorylase need to be regulated?
Because you cannot have glycogen being synthesised and broken down at the same time.
141
What is the type of regulation that glycogen synthase and glycogen phosphorylase have?
Reciprocal regulation.
142
How is hepatic glycogen synthase activated?
By glucose 6-phosphate.
143
How is glycogen synthase in the muscle activated?
By glucose-6-phosphate.
144
How is glycogen synthase in the muscle inhibited?
Ca2+.
145
What will be released to inhibit glycogen synthase during exercise?
Ca2+.
146
What inhibits hepatic glycogen phosphorylase?
Glucose-6-phosphate.
ATP.
Glucose.
147
How is glycogen phosphorylase in the muscle activated?
Calcium.
AMP.
148
How is glycogen phosphorylase in the muscle inhibited?
Glucose-6-phosphate.
ATP.
149
What enzyme is used to break down glucose in fight or flight situations?
Glycogen phosphorylase.
150
When will glycogen phosphorylase be used in the well fed state?
In fight or flight situations or during strenuous exercise.
151
What hormones activate glycogen synthase?
Insulin.
152
What hormones inhibit glycogen synthase?
Epinephrine.
Glucagon.
153
What will insulin use to activate glycogen synthase?
Phosphoprotein phosphatase.
154
What will glucagon or epinephrine use to inhibit glycogen synthase?
Protein kinase A.
Protein kinase C.
Calmodulin dependent kinase.
155
What hormones will activate glycogen phosphorylase?
Epinephrine.
Glucagon.
156
What will glucagon or epinephrine use to activate glycogen phosphorylase?
Protein kinase A.
Protein kinase C.
Calmodulin dependent kinase.
157
What hormones will inhibit glycogen phosphorylase?
Insulin.
158
What will insulin use to inhibit glycogen phosphorylase?
Phosphoprotein phosphatase.
159
What hormone is produced by the body in the fasting state?
Glucagon.
160
How does glucagon cause cellular changes?
Glucagon will bind to its GCPR and activate the CAMP pathway which will activate PKA.
161
What will the PKA activated by glucagon do?
Once activated, PKA will phosphorylate and activate glycogen synthase kinase
162
What does glycogen phosphorylase do once it is activated?
It will phosphorylate and inhibit glycogen synthase.
It will phosphorylate and activate glycogen phosphorylase.
163
The adding of a phosphate group to an enzyme is what kind of regulation?
Regulation by covalent modification.
164
When is glycogen synthase active?
When it is de-phosphorylated.
165
When is glycogen synthase inactive?
When it is phosphorylated.
166
When is glycogen phosphorylase inactive?
When it is de-phosphorylated.
167
When is glycogen phosphorylase active?
When it is phosphorylated.
168
Will glucagon have effects on muscle glycogen store or liver glycogen stores?
Liver.
Because, glucagon is released in the fasting state liver glycogen is broken down to buffer blood glucose levels.
169
If glycogen synthase is phosphorylated is it active or inactive?
Inactive.
170
If glycogen synthase is de-phosphorylated is it active or inactive?
Active.
171
If glycogen phosphorylase is phosphorylated is it active or inactive?
Active.
172
If glycogen phosphorylase is de-phosphorylated is it active or inactive?
Inactive.
173
If glycogen synthase kinase is phosphorylated is it active or inactive?
Active.
174
If glycogen synthase kinase is de-phosphorylated is it active or inactive?
Inactive.
175
What hormone is produced by the body in fight or flight situations or during strenuous exercise?
Epinephrine.
176
How will epinephrine affect glycogen metabolism?
Epinephrine binds to a GCPR which activates the cAMP or the phosphoinositol pathway.
Both pathways activate glycogen phosphorylase kinase to inhibit glycogen synthesis.
177
Can epinephrine can inhibit glycogen synthesis in the well fed state and in the fasting state?
Yes.
As the body needs to use all of the energy available to escape a life threatening situation.
178
Does epinephrine affect muscle and live glycogen stores?
Yes.
179
When epinephrine uses the phosphoinositol system, what other factors will help to inhibit glycogen synthesis and activate glycogenolysis?
Calcium ions.
Protein kinase C.
180
How do calcium ions activate glycogen degradation?
They bind to glycogen phosphorylase kinase and stimulate it to activate de-phosphorylated glycogen phosphorylase.
181
When is insulin produced by the body?
When the body is resting and in the well fed state.
182
How does insulin activate glycogen synthesis and inhibit glycogenolysis?
It activates an enzyme to cleave the phosphate from glycogen synthase.
183
Where do the calcium ions bind to on glycogen phosphorylase kinase to activate glycogenolysis?
The calmodulin subunit.
184
What insulin activated enzyme will cleave the phosphate from glycogen synthase?
Protein phosphatase-1
185
How does insulin affect the cAMP pathway to stop glycogenolysis?
It will activate phosphodiesterase which cleaves cAMP.
186
Is AMP produced in the fasting or well fed state?
In the fasting state.
187
How can AMP activate glycogenolysis in muscle cells?
It can activate de-phosphorylated glycogen phosphorylase.
188
What can activate de-phosphorylated glycogen phosphorylase?
AMP.
Calcium ions.
189
What ions are produced by muscle contraction?
Calcium.
190
How does calcium, activate glycogen degradation?
Calcium can bind to the calmodulin subunit of de-phosphorylated glycogen phosphorylase and activate it to break down glycogen.
191
What regulator in the blood during the fasting state will activate glycogen degradation in the liver?
Glucagon.
192
What pathway does glucagon use to activate glycogen degradation in the liver?
The cAMP pathway.
193
What regulator in the blood during the well fed state will activate glycogen synthesis in the liver?
Insulin.
194
What molecule activates the release of insulin?
Glucose..
195
What regulator in the blood during exercise and stress will activate glycogen degradation in the liver?
Epinephrine.
196
What molecules produced by epinephrine in the blood will activate glycogen degradation in the liver?
Ca2+.
Calmodulin.
197
What regulator in the blood during the fasting state will inhibit glycogen synthesis in the muscles?
Low insulin levels.
198
What regulator in the blood during the well fed state will activate glycogen synthesis in the muscles?
High insulin levels.
199
What regulator in the blood during exercise or stress will activate glycogen degradation in the muscles?
Epinephrine.
200
What molecules are used by epinephrine to activate glycogen degradation in the muscles?
AMP.
Ca2+.
Calmodulin.
201
If a person has an enzymatic disorder affecting liver glycogen, how will that affect the person?
They will become hypoglycaemic in the fasting state.
202
If a person has an enzymatic disorder affecting muscle glycogen, how will that affect the person?
They will have less energy during exercise.
203
A type 2 storage disorder is known as what disease?
Pompes disease.
204
A type 5 storage disorder is known as what disease?
McArdle syndrome.
205
A type 6 storage disorder is known as what disease?
Hers disease.
206
A type 1a storage disorder is known as what disease?
Van Gierkes disease.
207
What enzyme is affected in Pompes disease?
Lysosomal 𝛂-1,4 glucosidase deficiency.
208
What are the effects of Pompes disease?
It causes excessive glycogen levels in the lysosomes in heart, liver and muscle cells.
This leads to massive cardiomegaly which can be fatal at an early age.
209
What does the enzyme lysosomal 𝛂-1,4 glucosidase do?
It degrade glycogen in the lysosomes.
210
Will a persons blood glucose levels be normal if they suffer from Pompes disease?
Yes.
211
How can Pompes disease be treated?
By enzyme replacement therapy (ERT).
212
What enzyme is affected by McArdle syndrome?
Glycogen phosphorylase deficiency in skeletal muscle.
213
What does muscular glycogen phosphorylase do?
It cleaves glucose from glycogen in the muscles.
214
What is another name for muscular glycogen phosphorylase?
Myophosphoylase.
215
What are the effects of McArdles syndrome?
Muscular glycogen cannot be cleaved resulting in lower energy levels.
Muscle cramps are caused as lactate is never removed by the blood.
216
Are blood glucose levels affected by McArdles syndrome?
No.
217
When is lactate produced by muscles?
When they are exercising.
218
What usually happens to lactate when it is produced by muscles?
It is carried away by the blood.
219
What does a buildup of lactate in the muscles cause?
Cramps.
220
What enzyme is affected during Hers disease?
Glycogen phosphorylase in the liver
221
What are the effects of Hers disease?
It leads to hypoglycaemia when a person is fasting.
This condition is characterised by high levels of glycogen in the liver and an enlarged liver (hepatomegaly). Usually the affected person will be in ketosis and they will often suffer from a growth retardation.
222
What characterises Hers disease?
High levels of liver glycogen.
An enlarged liver (hepatomegaly).
223
What characterises McArdles syndrome?
High levels of muscle glycogen.
224
What enzyme is affected in Van Gierkes disease?
Glucose 6-phosphatase.
225
What are the effects of Van Gierkes disease?
Sufferers cannot release glucose into the blood and will suffer from hypoglycaemia.
People with this disease may suffer from growth retardation and a delayed onset in puberty.
226
What does glucose 6-phosphatase do?
It cleaves the phosphate group from glucose 6-phosphate in the ER of the liver.
227
What characterises Van Gierkes disease?
Enlargement of the liver and kidneys (hepatomegaly and renomegaly).
228
Does Van Gierkes disease affect the release of muscular glycogen?
No.
229
What enzyme is affected by type 1b glycogen storage disorder?
Glucose 6-phosphate translocase deficiency.
230
What are the effects of type 1b glycogen storage disorder?
Glucose cannot be released from the cell, resulting in the same symptoms as Van Gierkes disease.
231
What does glucose 6-phosphate translocase do?
It transports glucose 6-phosphate from the cytoplasm to the ER of the liver.
