Glucose Metabolism (complete) Flashcards
(243 cards)
1
Q
What is the primary source of glucose between meals
A
glycogenolysis of the hepatic glycogen
2
Q
What are the three sources of glucose that increase blood glucose
A
- dietary carbohydrates
- glycogen
- Lactate, amino acids, Glycerol
3
Q
What is the process of turning glycogen into glucose calles
A
glycogenolylsis
4
Q
what is the process of turning glucose in to glycogen called
A
glycogenesis
5
Q
what is the process of turning lactate, amino acids, and glycerol into glucose called
A
gluconeogenesis
6
Q
What are the two processes of glucose storage (these decrease blood glucose)
A
- glycogenesis
2. lipogenesis
7
Q
what is lipogenesis
A
the formation of triacylglycerols in the liver
8
Q
Where are the two most significant tissues that store glycogen
A
- the liver
2. skeletal muscle
9
Q
For what purpose does skeletal muscle do glycogenolysis
A
it does glycogenolysis to have glucose for its OWN energy
10
Q
for what purpose does the liver do glycogenolysis
A
the liver does glycogenolysis, then ships out the glucose for the rest of the body
11
Q
What kind of transporter carries glucose in and out of hepatic cells
A
GLUT-2
12
Q
is GLUT-2 an insulin dependent transporter
A
nope
13
Q
Where do glucose go first after it gets absorbed in the intestines
A
it goes to the liver
14
Q
What happens to glucose that is not absorbed in the liver
A
it goes out to the rest of the tissues
15
Q
What does the peak in blood glucose cause to happen
A
secretion of insulin
16
Q
where does insulin come from
A
pancreatic beta cells
17
Q
Which type of cells aren’t insulin dependent
A
red blood cells white blood cells lens and cornea of the eye liver brain
18
Q
what is the main function of insulin
A
causes the absorption of blood glucose into cells
19
Q
what is the transporter of glucose in the liver
A
GLUT-2
20
Q
Which types of cells are insulin dependent
A
Most tissues, particularly adipose and muscle tissue
21
Q
Which glucose transmitter is found in muscle and adipose cells
A
GLUT-4
22
Q
Which transporter is insulin dependent
A
GLUT-4
23
Q
What is the process of glucose uptake in cells that are insulin dependant after a carbohydrate meal
A
- a spike in blood glucose occurs
- spike in blood glucose causes secretion of insulin
- insulin binds its receptor
- this causes vesicles with GLUT-4 to move to, and fuse with the membrane
- the GLUT 4 now in the membrane transports glucose into the cell
24
Q
what is the process of glucose uptake in cells that are insulin dependent while fasting
A
- no spike in blood glucose
- this means no insulin secretion
- vesicles with GLUT-4 move away from the membrane
- less GLUT-4 in the membrane leads to less glucose absorption.
25
What is PKB and how does it affect the insulin/GLUT-4 process
1. insulin activates its receptor
2. its receptor sends a substrate of some sort to PKB
3. substrate activates PKB
4. PKB phosphorylates contractile elements to bring the vesicles with GLUT-4 to the membrane
26
What is diabetes mellitus
a group of disorders that have absolute or relative deficiencies of insulin
27
What do all types and disorders of diabetes exhibit
hyperglycemia (high blood sugar)
28
What is the process by which muscles get glucose while you are fasting
1. Muscle contraction uses ATP and gives off ADP and Pi
2. 2 ADP's are used by adenylate kinase to produce ATP and AMP
3. ATP is used up in contractions, but AMP levels in the cell rise
4. High AMP levels stimulate AMPK
5. AMPK causes the translocation of GLUT-4 vesicles to the membrane
29
What enzyme uses two ADPs to create ATP and AMP
adenylate kinase
30
what happens in muscle cells when AMP levels get high
AMPK is activated
31
What does AMPK do in muscles cells
it causes translocation of the GLUT-4 vesicles to the membrane
32
what is another way for muscle cells to bring the vesicles with GLUT-4 into the membrane besides insulin
muscular contractions (ATP--> ADP-->AMP-->AMPK-->translocation of GLUT-4 vesicles)
33
What is the first step of glucose metabolism regardless of the path that it will take
Reaction with glucokinase, or hexokinase into
| GLUCOSE-6-Phospate
34
What do kinases do
they phosphorylate things
35
Why is the phosphorylation of glucose into glucose-6-phosphate so important
1. glucose-6-phosphate it highly charged and polar. This makes it so it can't leave the cell
2. changing it from glucose maintains a concentration gradient or high glucose on the outside and low glucose on the inside so that the GLUTs can continue to bring glucose into the cell
36
Are GLUT transporters active or passive transporters
they are passive meaning that they work with a concentration gradient
37
What is hexokinase
a phosphorylating enzyme that converts glucose into glucose-6-phosphate.
38
where is hexokinase found
in all cells, including the liver
39
what is glucokinase
a phosphorylating enzyme that converts glucose into glucose-6-phosphate.
40
Where is glucokinase found
only in the liver
41
What is the Km of hexokinase
.2 mM
42
What is the Km of glucokinase
10mM
43
how is the high Km of glucokinase in comparison to the low Km of hexokinase significant
1. This means that Hexokinase has a much greater affinity to glucose than Glucokinase.
2. It also means that the speed at which hexokinase converts glucose into glucose-6-phosphate will be much less affected by decreases in blood glucose than Glucokinase.
44
What does the Km of a substance refer to
it refers to the amount of substrate that is needed to have the reaction at half of it's maximum speed (1/2 Vmax)
45
What is the normal range for blood glucose concentration
70-100 mg/dL
46
What is the concentration of blood glucose needed for hexokinase to be at it's half of it's maximum reaction speed (1/2 Vmax)
3.6 mg/dL
47
What does it mean that hexokinase will be at half of its maximum reaction speed when blood glucose is at 3.6 mg/dL
that hexokinase will be completely saturated, even when blood glucose is well below it's normal range, and an increase in blood glucose won't cause it to be more saturated.
(even when blood glucose is low or high, hexokinase will still be converting glucose into glucose-6-phosphate at a high rate)
48
What is the concentration of blood glucose needed for glucokinase to be at its half of maximum reaction speed (1/2 Vmax)
180 mg/dL
49
what does it mean that glucokinase will be at half of its maximum reaction speed when blood pressure is at 180mg/dL
that glucokinase will be well below saturation at normal blood glucose levels, and that a change in blood glucose levels will highly affect the saturation of, and the speed of reaction of glucokinase.
(when blood glucose is low, glucokinase activity is low. when blood glucose is high, glucokinase activity is high)
50
What does it mean that hexokinase is a constitutive enzyme
that it is always at optimal levels all of the time
51
What does it mean that glucokinase is an induced enzyme
that it is only at optimal levels in the presence of the inducer
52
what is the inducer of glucokinase
insulin
53
how does insulin induce glucokinase
by phosphorylation
54
Is hexokinase inhibited by glucose-6-phosphate
yes
55
is glucokinase inhibited by glucose-6-phosphate
no
56
In people with type 1 diabetes how would the activity of glucokinase be
it would be low because the synthesis of glucokinase is induced by insulin
57
When is glucokinase activity high
shortly after a carbohydrate meal
58
When is glucokinase activity low
between meals/when fasting
59
when is hexokinase activity high
it's always constant (except in very severe cases of hypoglycemia)
60
How active do we want glucokinase while we are fasting
we want it inactive while we are fasting, so that more glucose can be sent out to the body
61
What keeps glucokinase inactive while we are fasting
glucokinase regulatory protein binds to glucokinase inactivating it
62
Where is glucokinase located when bound to the glucokinase regulatory protein
in the nucleus
63
what causes glucokinase to be released from the glucokinase regulatory in the protein
a rise in glucose levels in the cell, due to a rise in blood glucose levels after a meal
64
What causes glucokinase to be sent back into the nucleus and to be bound and inactivated by glucokinase regualtory protein
an increase in concentration of fructose-6-phosphate in the cell (an intermediate in glycogenesis)
65
What besides glucose in the cell can cause glucokinase to be released by glucokinase regulatory protein
an increase in concentration of fructose-1-phosphate in the cell (from fructose)
66
What begins to occur when we are fasting that causes glucokinase to be bound by glucokinase regulatory protein
gluconeogenesis
67
what about gluconeogenesis causes glucokinase to be bound by glucokinase regulatory protein
in gluconeogenesis, Amino Acids, lactate, glycerol, and pyruvate are converted into fructose-6-phosphate (on their way to becoming glucose) this is what causes glucokinase regulatory protein to bind glucokinase
68
What affect does insulin have on glucokinase
Insulin induces glucokinase by upregulating the production of it
69
How does insulin influence the absorption of blood glucose into the liver
it doesn't directly assist in bringing in glucose. But it does induce glucokinase, which converts glucose into glucose-6-phosphate when it enters the cell. this keeps the glucose concentration low in the cell and the glucose gradient pushes glucose into the cell
70
Which enzyme would be better for the brain, glucokinase or hexokinase
hexokinase, because it has a higher affinity for glucose and is always active, even in low blood glucose levels. Glucokinase would be bad because it is only active in high blood glucose levels
71
is someone with defective glucokinase, with low activity, considered diabetic, Why?
Yes, because they would have a decreased ability to phosphorylate Glucose and thus less glucose would enter the liver, and more would stay in the blood
72
in the final step of glycogenolysis and gluconeogenesis what is the benefit of controlling glucokinase by it binding to GKRP
glycogenolysis and gluconeogenesis are attempting to make glucose, if glucokinase weren't controlled it would be working in oppposition to these, turning glucose back into glucose-6-phosphate
73
Which has a higher Km glucokinase, or hexokinase
glucokinase
74
Is hexokinase or glucokinase inhibited by glucose-6-phosphate
hexokinase
75
Which tissue uses the GLUT-2 transporter, liver or muscle
liver
76
which tissue has glucokinase, liver or muscle
liver
77
What are the steps of glycogenesis
1. glucokinase/hexokinase convert glucose into glucose-6-phosphate
2. glucose-6-phosphate is isomerized into glucose-1-phosphate by phosphoglucomutase
3. glucose-1-phosphate and UTP are combined to form UDP-glucose and PPi
4. PPi is hydrolized to form two molecules of inorganic phosphate Pi
5. The Glucose end of UDP-glucose is transferred to a glycogen primer at the non-reducing end by glycogen synthase
78
What is a glycogen primer
it is a protein molecule on the reducing end, with a few glucose molecules bound by alpha 1-4 bonds.
79
When we use up glycogen in fasting, do we use all of our glycogen that we have stored
no, we leave a little bit as a primer
80
To which end of a glycogen chain or glycogen primer do we add new glucose molecules (from UDP-glucose via glycogen synthase)
the non-reducing end
81
What kind of bond is created between the glucoses of glycogen
Alpha 1-4
82
What happens to the UDP-portion of UDP-glucose after glucose is added to the existing glycogen chain
nucleoside diphosphokinase transfers the terminal phosphoryl from ATP to UDP regenerating the UTP we need to create UDP-Glucose
83
What happens if there are no glycogen primers upon which to add more molecules of glucose (from UDP glucose)
the protein Glycogenin can serve as an acceptor of the glucose molecules
84
What is the structure of glycogenin
it is a dimer, in which there are receptor tyrosine residues on each end (head and toe), these tyrosine residues bind a few glucose molecules from UDP glucose, then glycogen synthase adds more to it
85
what happens to glycogenin after a long glycogen chain has been added
it remains attached to the glycogen strand
86
is ATP used in glycogenesis
Yes
87
how many ATPs are used in each round (addition of one glucose) of glycogenesis
2 ATP are used
88
in which steps of glycogenesis is ATP used
1. glucose to glucose-6-phosphate by glucokinase or hexokinase
2. UDP to UTP
89
Is glycogen branched or not
it is branched
90
What enzyme is used in the branching of glycogen
the branching enzyme (glucosyl 4:6 transferase)
91
What kind of bond is used between the branches of glycogen
alpha 1-6 bond
92
How does branching of glycogen happen
the branching enzyme cleaves off 5-8 of the glucoses on the non reducing end of a glycogen strand and transfers it to an interior portion of the glycogen
93
What type of end does the branching of glycogen create more of? reducing or non reducing
non reducing
94
why is it significant that many non reducing ends are created in the branching of glycogen
because that means that there are many more non-reducing ends to which more glucose can be attached
95
How many more non-reducing ends are made per each new branch of glycogen made
1 non-reducing end per branch of glycogen formed
96
How close can a new branch of glycogen be added to an existing branch point of glycogen
the new branch of glycogen needs to be at least 4 units away from the existing branch point
97
Why does the cell store glycogen instead of glucose
because glucose is osmotically active and if there were too high of concentrations in the cell, then the cell would lyse (tear/blow up and die)
98
What is glycogenolysis
the breakdown of glycogen into glucose
99
What are the three enzymes used in glycogenolysis
1. glycogen phosphorylase
2. Debranching enzyme
3. phosphoglucomutase
100
What enzyme is both found in glycogenolysis and glycogenesis
phosphoglucomutase
101
What is the first step of glycogenolysis
glycogen phosphorylase acts on the non-reducing ends of glycogen and breaks the most terminal alpha 1-4 bond and phoshorylates the C1 of glucose to make glucose-1-phosphate
102
What is the first enzyme used in glycogenolysis
glycogen phosphorylase
103
what bonds does the glycogen phosphorylase break
the terminal most alpha 1-4 bond on the non-reducing end
104
what bonds aren't broken by glycogen phosphorylase
the alpha 1-6 bonds between branches, and any alpha 1-4 bond that is 4 units away or closer to a branch point
105
What is left after glycogen phosphorylase has worked on glycogen
Glucose-1-phosphate and a branched glycogen with branches that are 4 units long
106
What enzyme comes in and works on the branched glycogen after glycogen phosphorylase
the Debranching enzyme
107
What are the two catalyltic activities of the debranching enzyme
1. Transferase activity
| 2. alpha 1-6 glucosidase activity
108
How does the debranching enzyme cleave the bonds of the 4-unit branched glycogen
1. it transfers the 3 units linked by alpha 1-4 bonds to the non reducing end of the opposing unit branch, making a 1 unit branch and a 7 unit branch
2. the glucosidase portion of the debranching enzyme cleaves the alpha 1-6 bond of the branch point (releases a free glucose molecule)
109
What is the first step of the debranching of glycogen
the transferase portion of the debranching enzyme transfers the 3 unit portion of a glycogen strand (leaves the one glucose bound to the other branch by an alpha 1-6 bond) to the non-reducing end of another 4 unit branch
110
what is left of two 4 unit branches of glycogen after the debranching enzyme has done its transferase portion
there is a 7 unit branch, and a 1 unit branch
111
what does the glucosidase portion of the debranching enzyme do
it cleaves the alpha 1-6 bond between the single glucose and the longer glycogen branch
112
How many glucoses are freed by the debranching enzyme per branch that the debranching enzyme debranches.
one (the glucose that had formed the alpha 1-6 bond as a branch point)
113
which enzyme in glycogenolysis releases more glucose molecules, the glycogen phosphorylase or the debranching enzyme
the glycogen phosphorylase
114
what happens after the debranching enzyme gets rid of the branching in glycogen
glycogen phosphorylase begins removing a single unit (glucose 1 phosphate) from the non-reducing end of the linear glycogen chain
115
What happens to all of the glucose-1-phosphate in the cell following the glycogen phosphorylase and debranching enzyme actions of glycogenolysis
phosphoglucomutase converts glucose-1-phosphate into glucose-6-phosphate
116
Is the phosphoglucomutase step a reversable one
yes
Glycogenesis: converts Glucose-6-P into Glucose-1-P
Glycogenolysis: converts glucose-1-P into Glucose-6-P
117
What is the difference between glycogenolysis in the liver and the muscle
the presence of glucose-6-phosphatase
118
what does glucose-6-phosphatase do
it converts glucose-6-phosphate into glucose
119
In which tissue does glucose-6-phosphatase exist? muscle or liver
liver
120
what does the presence of glucose-6-phosphatase allow the liver to do that muscle cannot
it creates free glucose that can be released in the blood, and travel to other tissues. The liver can do this, the muscle cannot
121
What are the two enzymes that regulate glycogenesis and glycogenolysis
Glycogen synthase
| Glycogen phosphorylase
122
Why do we need to regulate glycogenesis and glycogenolysis
because it would be a futile cycle if they were both running. One creates glucose from glycogen, the other created glycogen from glucose
123
What do we want the activity of glycogen synthase and glycogen phosphorylase to be like during fasting
we want high glycogen phosphorylase activity and low glycogen synthase activity
124
What do we want the activity of glycogen synthase and glycogen phosphorylase to be like after a carbohydrate meal
we want glycogen synthase to be high and glycogen phosphorylase activity to be low
125
What are the two things that control and regulate the activity of glycogen synthase and glycogen phosphorylase
Hormones and allosteric factors
126
How do hormones affect the activity of glycogen synthase and glycogen phosphorylase
they either cause phosphorylation or dephosphorylation of the two enzymes, this changes whether they are active or not.
127
What are the two enzymes responsible for phosphorylation and dephosphorylation of glycogen synthase and glycogen phosphorylase
phosphatase and kinase
128
does the kinase phosphorylate or dephosphorylate
it phosphorylates
129
does the phosphatase phosphorylate or dephosphorylate
it dephosphorylates
130
when is glycogen synthase active
when it isn't phosphorylated
131
when is glycogen phosphorylase active
when it is phosphorylated
132
What must the activity of the kinase and phosphatase be if we want to glycogen synthase to be active
the kinase needs to be inhibited and the phosphatase needs to be activated.
133
What must the activity be of the kinase and the phospatase if we want glycogen phosphorylase to be inactive
the kinase needs to be inhibited and the phosphatase needs to be activated
134
what must the activity of the kinase and the phosphatase be if we want glycogen phosphorylase to be active
the kinase needs to be active and the phosphatase needs to be inactive
135
what must the activity of the kinase and the phosphatase be if we want glycogen synthase to be inactive
the kinase needs to be active and the phosphatase needs to be inactive
136
If we want glycogenesis to occur what must the activity of the kinase and the phosphatase be
the kinase needs to be inactive and the phosphatase needs to be active
137
if we want glycogenolysis to occur what must the activity of the kinase and the phosphatase be
the phosphatase needs to be inactive and the kinase needs to be active
138
in glycogenesis are glycogen synthase and glycogen phosphorylase phosphorylated or dephosphorylated
they are dephosphorylated
139
in glycogenolysis are glycogen synthase and glycogen phosphorylase phosphorylated or dephosphorylated
the are phosphorylated
140
When we are fasting are glycogen synthase and glycogen phosphorylase phosphorylated or not
they are phosphorylated
141
after a carbohydrate meal are glycogen synthase and glycogen phosphorylase phosphorylated or not
they aren't phosphorylated
142
What is the name of the kinase enzyme that when active keeps glycogen phosphorylase active and phosphorylated,
phosphorylase kinase
143
What is the name of the phosphatase that causes dephosphorylation of glycogen synthase and glycogen phosphorylase
phosphoprotein phosphatase-1
144
What directly regulates the activity of phosphoprotein phosphatase-1
Phosphoprotein phosphatase-1 inhibitor
145
How does phosphoprotein phosphatase-1 inhibitor inhibit phosphoprotein phosphatase-1
when phosphoprotein phosphatse-1 inhibitor is activated it binds to phosphoprotein phosphatase-1 and inactivates it.
146
What are the three major hormones that affect the activity of glycogen synthase and glycogen phosphorylase
glucagon, insulin, and epinepherin
147
Which hormone(s) cause phosphorylation of glycogen synthase and glycogen phosphorylase
epinepherin and glucagon
148
Which hormone causes dephosphorylation of glycogen synthase and glycogen phosphorylase
insulin
149
Where is glucagon from
pancreatic alpha cells
150
What is the main stimulant of the release of glucagon
low blood glucose
151
What tissues does glucagon act on when it comes to glycogenesis and glycogenolysis
the liver only
152
What is the end result of glucagon on the liver
the breakdown of glycogen into glucose that can be released into the blood
153
Where is epinepherine from
the adrenal medulla
154
What causes epinepherine to be released
truama, stress, and physical activity
155
What tissues does epinepherine act on when it comes to glycogenesis and glycogenolysis
The liver and muscles
156
What does epinepherine cause in the muscles and liver
glycogenolysis
157
What are the steps from secretion of epinepherine and glucagon to the end start of glycogenolysis
1. the hormones bind their receptors activating adenyl-cyclase
2. Adenylate cyclase converts ATP to cAMP
3. cAMP binds to protein kinase A (PKA) and activates it
4. PKA phosphorylates and activates phosphorylase kinase (which phosphorylates glycogen phosphorylase to activate it)
5. PKA phosphorylates and deactivates glycogen synthatse
6. PKA also phosphorylates and activates phosphoprotein phosphatase inhibitor-1
7. phosphoprotein phosphatase inhibitor-1 binds phosphoprotein phospatase-1 and inactivates it (keeping both glycogen synthase and glycogen phosphorylase phosphorylated)
158
What are the three main kinases that can phosphorylate and deactivate glycogen synthase
1. PKA
2. Phosphorylase kinase
3. Glycogen synthase 3
159
What enzyme is activated by the binding of epinepherine and glucagon
adenylate-cyclase
160
What does adenylate cyclase do
converts ATP to cAMP
161
what does cAMP do in glycogenolysis
activates protein kinase A (PKA)
162
What is the structure of PKA
it is a tetramer with two catalytic and two regulatory subunits
163
What causes the subunits of PKA to separate
binding of 2 cAMP to each of the regulatory subunits, this causes the four subunits to separate
164
is the tetramer form of PKA active, or is the separated form active
when the subunits are separate it is active, when they are together PKA is inactive
165
How many cAMPs must bind to PKA to cause the subunits to separate and become active
4, two to each of the regulatory subunits
166
What are the three things that PKA can do once it has become an active monomeric unit
1. phosphorylates glycogen synthase and keeps it inactive
2. phosphorylates phosphorylase kinase, which then phosphorylates glycogen phosphorylase to keep it active
3. phosphorylates the inhibitor protein, which binds to and inhibits phosphoprotein phosphatase-1 and inhibits it from dephosphorylating glycogen synthase and glycogen phosphorylase
167
We know that PKA phosphorylates glycogen synthase, what other enzymes can phosphorylate glycogen synthase and inactivate it?
Phosphorylase kinase
| Glycogen Synthase Kinase-3 (GSK-3)
168
Which hormones can initiate the cAMP/PKA route to glycogenolysis
glucagon and epinepherine
169
Which hormone can initiate the calcium calmodulin route to glycogenolysis
epinepherine
170
To what receptor does epinepherine bind to in order to initiate the cAMP/PKA route to glycogenolysis
it binds to the Beta-adrenergic receptor
171
to what receptor does epinepherine bind to in order to initiate the calcium calmodulin route to glycogenolysis
it binds to the alpha receptors in the liver
172
What are the steps of upregulating glycogenolysis and inhibiting glycogenesis initiated by epinepherine binding to the alpha receptors in the liver
1. epinepherine binds to alpha receptors
2. this activates phospholipase C (PLC)
3. Phospholipase C hydrolizes PIP into DAG and IP3
4. IP3 stimulates the release of calcium from the endoplasic reticulum
5a. Ca++ and DAG activate Protein kinase C
5b. Calmodulin also binds Ca++ and Ca-Calmodulin levels increase
6. Ca-calmodulin activates phosphorylase kinase and calmodulin dependent protein kinase.
7. Phosphorylase kinase, protein kinase C, and calmodulin dependent protein kinase all phosphorylate and inactivate glycogen synthase
8. Phosphorylase kinase also phosphorylates (and Activates) glycogen phosphorylase
173
In the process of upregulating glycogenolysis and inhibiting glycogenesis initiated by epinepherine binding to the alpha receptors in the liver. what happens directly after epinepherine binds
Phospholipase C is activated and hydrolizes PIP into DAG and IP3
174
What are the products given off of the reaction between phospholipase C and PIP
DAG
| IP3
175
What does DAG go on to do after it and IP3 came from the hydrolysis of PIP by Phospholipase C
DAG goes onto to activate Protein Kinase C
176
What Does IP3 go on to do after it and DAG came from the hydrolysis of PIP by phospholipase C
IP3 goes on to stimulate the release of Ca++ from the endoplasmic reticulum
177
What does Ca++ go on to do after it's release from the endoplasmic reticulum was stimulated by IP3
1. it goes on to activate protein kinase C (along with DAG)
| 2. It gets bound by calmodulin to make Ca-calmodulin
178
What does protein kinase C do after it is activated by Ca++ and DAG
it phosphorylates and inactivates glycogen synthase
179
What does Ca-Calmodulin in the cell
1. it activates calmodulin dependent protein kinase
| 2. it activates phosphorylase kinase
180
What does calmodulin dependent protein kinase go on to do after it has been activated by ca-calmodulin
it phosphorylates and inactivates glycogen synthase
181
What does phosphorylase kinase go on to do after it has been activated by Ca-calmodulin
1. it phosphorylates and inactivates glycogen synthase
| 2. it phosphorylates and activates glycogen phosphorylase
182
what are the effects of insulin on the hepatic glycogen metabolism in comparison to the effects of glucagon
insulin does the opposite. insulin reverses all of the effects of glucagon on hepatic glycogen metabolism
183
In what ways does insulin inhibit glycogenolysis and stimulate glycogenesis
1. Limits the production of cAMP
2. activates hepatic protein phosphatases
3. activates the phosphodiesterase that converts cAMP to AMP
4. inactivates glycogen synthase kinase 3
184
how does the limiting of the production of cAMP by insulin decrease glycogenolysis and increase glycogenesis
cAMP goes onto to activate PKA,
PKA inactivates glycogen synthase
PKA activates glycogen phosphorylase (through phosphorylase kinase)
PKA also activates phosphatase inhibitors (those inhibit phosphatases, keeping things phosphorylated)
Without cAMP those things don't happen
185
How does the activation of protein phosphatases by insulin decrease glycogenolysis and increase glycogenesis
protein phosphatases dephosphorylate both glycogen synthase and glycogen phosphorylase
glycogen synthase is now active
glycogen phosphorylase is now inactive
186
how does the inactivation of glycogen synthase kinase 3 by insulin decrease glycogenolysis and increase glycogenesis
glycogen synthase kinase 3 phosphorylates and inactivates glycogen synthase, keeping it inactive. So when it is inactive, glycogen synthase becomes more active
187
What are the levels of insuiln and glucagon like after a carbohydrate meals
insulin is high and glucagon is low
188
What does the high insulin levels and low glucagon levels after a carbohydrate meal lead to in terms of glycogen metabolism
it leads to increased glycogenesis (glycogen synthesis) and decreased glycogenolysis (glycogen degredation)
189
What are the levels of insulin and glucagon like during fasting
insulin levels are low, and glucagon levels are high
190
what does the high glucagon levels and low insulin levels during fasting lead to in terms of glycogen metabolism
it leads to increased glycogenolysis (glycogen breakdown) and decreased glycogenesis (glycogen synthesis)
191
besides hormonal regulation of the of glycogen metabolism, what is the other type of regulation of glycogen metabolism
allosteric regulation
192
what is allosteric regulation of glycogen metabolism
the influence of metabolite levels and the energy status of the cell on glycogen synthase and glycogen phosphorylase
193
which type of glycogen metabolism regulation can override the other? hormonal or allosteric
allosteric regulation can override hormonal regulation
194
What allosteric factors inhibit glycogenolysis and increase glycogenesis in the liver
1. glucose
2. glucose-6-P
3. ATP
195
Why does high levels of glucose in the cell inhibit glycogenolysis and increase glycogenesis in the liver
if there is an excess of glucose in the cell, then we don't want to break down glycogen to make more of it, but store more of it as glycogen
196
Why do high levels of glucose-6-Phosphate in the cell inhibit glycogenolysis and increase glycogenesis in the liver
just like glucose, if there is an excess of glucose-6-P in the cell then we will use it to make glycogen, not break glycogen down to create more of it.
197
Why do high levels of ATP in the cell inhibit glycogenolysis and increase glycogenesis in the liver
because high levels of ATP indicate that the cell is at a high energy state. so the breakdown of glycogen to create more ATP isn't necessary
198
What are the allosteric factors that inhibit glycogenolysis and increase glycogenesis in the muscle
1. ATP
| 2. Glucose-6-phosphate
199
What are the allosteric factors that inhibit glycogenesis and increase glycogenolysis
1. Ca++
| 2. AMP
200
In muscle is glucose an inhibitor of glycogen phosphorylase
No
201
Why isn't glucose an inhibitor of glycogen phosphorylase
because the amount of glucose in the cell doesn't get high because once it enters the cell hexokinase converts it into glucose-6-phosphate
202
In muscle, how many different ways are there to increase activation of glycogen phosphorylase
3
203
what are the 3 ways in muscle to increase activation of glycogen phosphorylase
1. Increased levels of AMP
2. Nerve inpulses
3. Epinepherine
204
How do we get increased levels of AMP in the muscle, anb how does that lead to activation of glycogen phosphorylase
During contraction the muscle uses up ATP and gives off AMP. As these AMP levels rise AMP binds to glycogen phosphorylase and activates it without phosphorylating it
205
How do nerve inpulses lead to activation of glycogen phosphorylase in muscle
Nerve impulses cause Ca++ to be released from the sacrcoplasmic reticulum. then the Ca++ binds to calmodulin, and then Ca-Calmodulin activates phosphorylase kinase, and phosphorylase kinase activates glycogen phosphorylase
206
How does epinepherine cause increased activation of glycogen phosphorylase in muscle
epinepherine binds to its receptor and activates adenylate cyclase, this creates cAMP and cAMP activates PKA. PKA then inactivates glycogen synthase, activates the inhibitor than inhibits the phosphatase from deactivating glycogen phosphorylase, and lastly it activates phosphorylase kinase to activae glycogen phosphorylase.
207
How does glycogen regulate glycogen synthesis
1. it inhibits the formation of glycogen by making the active form of glycogen synthase a better substrate for protein kinase A
2. it also inhibits the phosphoprotein phosphatase from dephosphorylating glycogen synthase, keeping it inactive, and not letting more glycogen be stored.
208
What are the 5 types of glycogen storage disorders that we need to know
```
1 - Von Gierke's disease
3 - Cori's disease
4 - Anderson disease
5 - McArdle's disease
6 - Her's disease
```
209
What is the defective enzyme in Von Gierke's disease (type 1 glycogen storage disorder)
Glucose-6-phosphatase
210
What is the problem with having a defect in glucose-6-phosphatasee like in glycogen storage disorder type 1, Von Gierke's disease.
because glucose-6-phosphatase is defective, the liver can't go from glucose-6-phosphate back to glucose. so the liver can't ship glucose out to the rest of the body.
211
What are problems that arise in glycogen storage disorder type 1, Von Gierkes disease
Being unable to reproduce glucose from glucose-6-phosphatase leads to:
- Massive enlargement of the liver
- Failure to thrive
- Severe hypoglycemia
- Ketosis
- Hyperuricemia
- Hyperlipemia
212
What organs are most affected by glycogen storage disorder type 1. Von gierke's disease
liver and kidney
213
How is glycogen storage levels affected with type 1 glycogen storage disorder von gierke's disease
the levels of glycogen are increased
214
What is the defective enzyme in type 3 glycogen storage disorders, Cori's disease
The debranching enzyme
215
What is the problem that arises with having a defecting debranching enzyme for glycogen, like in type 3 glycogen storage disorder, Cori's disease
if you can't debranch the glycogen, then you will be unable to break it down enough. so there will be extra glycogen because we don't break it down enough
216
What are the problems that arise in Type 3 glycogen storage disorder, Cori's disease
They are all similar to type 1 Von Gierke's disease, just milder
- increased liver size
- hypoglycemia
- ketosis
- hyperuricemia
- hyperlipemia
217
What organs are affected by Type 3 Glycogen storage disorder, Cori's disease
The muscle and liver
218
How are the levels of glycogen affected by type 3 glycogen storage disorder, Cori's diseas
increased amount of glycogen
| Shorter outer branches
219
What is the enzyme that is defective in type 4 glycogen storage disorder, Andersen's disease
The Branching enzyme
220
What happens to a person with type 4 glycogen storage disorder, Andersen's disease
they usually have liver failure at age 2 and pass away
221
What tissue is affected by andersen's disease, type 4 glycogen storage disorder
the liver
222
What is the glycogen storage like for someone with andersen's disease, Type 4 glycogen storage disorder
it has very long outer branches
223
What is the enzyme that is defective in type 5 glycogen storage disorder, McArdle's disease
phosphorylase (in the muscle)
224
What happens to a person with McArdle's disease, type 5 glycogen storage disorder
they are unable to do strenuous exercise because of painful muscle cramps, otherwise they are normal
225
What tissue is affected by McArdle's disease (Type 5)
the muscle
226
what is the glycogen like in someone with McArdles disease
pretty normal, but slightly increased amounts
227
What is the enzyme that is bad in type 6 glycogen storage disorder, Her's disease
phosphorylase (in the liver)
228
What happens to the person with type 6 glycogen storage disorder, Her's disease
they have the same symptoms as someone with Von Gierke's disorder, just more mild
- enlarged liver
- hypoglycemia
- ketosis
- hyperuricemia
- hyperlipemia
229
What tissues are affected in Her's disease (type 6 glycogen storage disorder)
the liver
230
what is the glycogen storage like in someone with Her's disease
increased amount of glycogen
231
1. Muscle glycogen cannot contribute directly to blood glucose because:
A. Muscle glycogen can't be converted to glucose-6-P
B. Muscle lacks glucose-6-phosphatase
C. Muscle contains no glycogen phosphorylase
D. Muscle lacks phosphoglucomutase
B
232
Type I glycogen storage disease (Von Gierke’s Disease) is associated with severe fasting hypoglycemia. This is due to:
A. the inability of the liver to release the glucose into the blood.
B. the inability of the liver to synthesize glycogen.
C. a deficiency of glycogen phosphorylase in the liver.
D. A and B are correct.
E. A, B, and C are correct.
A
233
3. Which of the following enzymes involved in glycogen metabolism would be active if the insulin/glucagon ratio is extremely low?
```
A. Glycogen phosphorylase
B. Phosphorylase kinase
C. Glycogen synthase
D. A and B are correct
E. A, B, and C are correct.
```
D
234
Which of the following enzymes involved in glycogen metabolism will be phosphorylated during fasting (interval between meals)?
```
A. Glycogen phosphorylase
B. Glycogen synthase
C. Protein kinase A
D. A and B are correct
E. A, B, ad C are correct
```
D
235
McArdle’s Disease (Type V Glycogen Storage Disease) is characterized by a limited ability to perform strenuous exercise because of painful muscle cramps. The cause of this condition is a congenital deficiency of:
```
A. glucose-6-phosphatase in the liver
B. glycogen phosphorylase in the liver
C. glycogen phosphorylase in the muscle
D. branching enzyme in the liver
E. debranching enzyme in the muscle
```
C
236
6. An individual is born with a defective protein phosphatase inhibitor. What effect would such a disorder have on glycogen metabolism?
Increased glycogen synthesis
237
5. Caffeine is a phosphodiesterase inhibitor. What effect would the consumption of several cups of coffee have on glycogen metabolism?
this gives rise to more cAMP, this activates protein kinase A, which activates glycogen phosphorylase
238
4. If an individual is born with a GLUT-2 deficiency, would you expect him/her to have fasting hypoglycemia? Explain.
Yes, because the liver can’t transport glucose out in to the blood
239
3. There is a strain of mice that is deficient in muscle phosphorylase kinase. Phosphorylase b in muscle of such mice cannot be converted into phosphorylase a. Nevertheless, heavy exercise results in depletion of muscle glycogen. Explain.
Muscle contraction uses ATP and creates ADP, this then goes to AMP, AMP binds directly to glycogen phosphorylase activating it, even though it may not be phosphorylated
240
2. If glycogen inhibits its own formation, why do you see massive accumulation of glycogen in Von Gierke’s Disease (Type I Glycogen Storage Disease)?
Because it can’t turn glucose-6-phosphate into glucose, and glucose-6-phosphate is a positive influence on glycogen synthase and a negative influence on glycogen phosphorylase. This even happens if the glycogen synthase is phosphorylated and in its inactive.
241
1. Compared to glucokinase, hexokinase:
```
A. is a constitutive enzyme.
B. is found in all tissues.
C. is inhibited by glucose-6-P.
D. a and b are correct.
E. a, b, and c are correct.
```
E
242
2. Compared to hexokinase, glucokinase:
```
A. is a constitutive enzyme.
B. is found in all tissues.
C. is inhibited by glucose-6-P.
D. is not specific for glucose.
E. has a higher KM.
```
E
243
This enzyme is present in all tissue types (hexokinase Vs. glucokinase)
Hexokinase
