Signal Transduction Flashcards
(111 cards)
1
Q
List 3 properties of carriers
A
- Slow transport rate
- Saturable
- Active and passive
2
Q
List 3 properties of channels
A
- Very fast transport rate
- Not saturable
- Passive
3
Q
Na/K ATPase does what?
A
Pumps 3 Na out against conc gradient
2 K in against conc gradient
(Na is already out and K is already in)
4
Q
Ca ATPase does what?
A
Pumps Ca 2+ out of cytosol
Across plasma membrane and ER
5
Q
Na/K ATPase is responsible for high levels of ___ outside cell and high levels of ____ inside cell
A
Na/K ATPase is responsible for high levels of Na outside cell and high levels of K inside cell
6
Q
Ca ATPase is responsible for what?
A
For maintaining low Ca inside the cell (cytosol) and high Ca outside
7
Q
For Cl, there are high levels _____ and low levels ____ cell
A
outside; inside
8
Q
When membrane potential becomes more positive, what is it called?
A
Depolarization
9
Q
When membrane potential becomes more negative, what is it called?
A
Polarization
10
Q
Impermeant channels generate
A
No electrical potential
11
Q
Pearmeant channels generate
A
Electrical potential
12
Q
Cells communicate via what?
A
Chemical messengers
13
Q
2 examples of ion chemical messengers
A
- Blood Ca 2+
- Cytosolic Ca 2+
14
Q
2 functions of ion chemical messengers
A
- Ca 2+ homeostasis
- 2nd messenger in cytosol
15
Q
Examples of metabolite chemical messenger
A
Glucose (doesn’t bind to a receptor)
16
Q
Function of metabolite chemical messenger
A
Insulin release from pancreas
Glycolysis produces ATP which regulates ion channels and insulin release
17
Q
2 examples of hormone chemical messengers
A
- Glucagon
- Insulin
18
Q
Function of hormone chemical messengers
A
Regulate metabolic homeostasis
19
Q
Example of growth factor chemical messenger
A
Epidermal Growth Factor (associated with oral cancer)
20
Q
Function of growth factor chemical messenger
A
Stimulates cell growth
21
Q
Insulin tells our tissues we are _____ _____ ______
A
Fed with glucose
22
Q
What are signals telling us we aren’t fed?
A
Glucagon and epinephrine
23
Q
3 fed steps
A
- Liver puts out glucose when we’re fasting
- Glucagon and epinephrine are signals telling liver to release glucose to blood
- Insulin lowers blood glucose by stimulating uptake in adipose and muscle
24
Q
4 Steps of signal changes by binding to receptors
A
- Cells secrete chemical messengers in response to changes in environment
- Messenger diffuses/transported through blood
- Messenger specifically binds to receptor on target cell (receptor can be in cell/on surface)
- Binding to receptor elicits cellular response
25
Chemical messengers that bind to cell surface receptors generate what?
2nd messenger inside cell
26
1st message
Chemical messenger binds to cell surface receptor
27
2nd message
Generated in response to 1st messenger binding to cell surface receptor
28
What do changes in 2nd messenger levels cause?
Changes in protein activity in cell?
29
Are 2nd messenger in cell present in high or low levels?
Low
30
Why are 2nd messengers present in low levels?
So small changes can have big effect
31
List 3 classes of cell surface receptors
1. Ion channels
2. Tyrosine kinase receptors
3. G-protein coupled receptors
32
Examples of ion channels
1. cytosolic Ca 2+, membrane potential
2. insulin release
33
Examples of tyrosine kinase receptors
1. insulin
2. Epidermal growth factor (EGF)
3. GH, PRL, associated JAK kinases
34
Examples of G-protein coupled receptors
1. Epinephrine, glucagon
2. cAMP, IP3/DAG/Ca 2+
35
Energy consuming processes pump Ca ____ _____ ____ against a large unfavourable gradient for Ca 2+
out of cytosol
36
What is gradient for Ca 2+ to enter cytosol?
~10 000 to 1
37
Ca 2+ channels allow Ca 2+ ions to diffuse through cell membrane....
Down its electrochemical gradient
38
Ca 2+ channel 4 steps
1. Cytosolic Ca 2+ low in a cytosol at rest. Membrane potential is polarized/-
2. Depolarization increases cell activity
3. Depolarization causes Cav channels to open
4. Cav channels allow Ca 2+ to flow into cytosol
39
Ca 2+ channels _____ regulate cytosolic Ca 2+
directly
40
Potassium channels _____ regulate cytosolic Ca 2+ by changing Vm
indirectly
41
Active/open K channels _______ Vm, causing Cav to _____. Less Ca 2+ enters cytosol
polarize (bc K going out); close
42
Inactive/closed K channels ______ Vm, causing Cav to ______. More Ca 2+ enters cytosol
depolarize (lots of K in); open
43
ATP gated K channels couple high blood glucose to...
Insulin release in pancreatic beta cells
44
When are Katp channels open/active?
When ATP in cell is low bc polarized Vm, less Ca 2+ enters cytosol
45
When are Katp channels closed/inactive?
When ATP in cell is high bc depolarized Vm, more Ca 2+ enters cytosol
46
What stimulates insulin release?
Cytosolic Ca 2+
47
What inhibits the ATP-gated K channel, depolarizing Vm?
ATP
48
ATP increases in response to what?
Increased glucose
49
High ATP -> membrane _____
Depolarized
50
Low ATP -> membrane _____
Polarized
51
Ion channels couple glucose catabolism and ATP to...
Insulin release from pancreatic beta cells
52
How does glucose enter beta cells?
Through GLUT2 transporter
53
Which channels does ATP generated from catabolism close?
Katp channels
54
Reduced K+ efflux -> _______ membrane
depolarizes
55
What opens Cav?
Depolarization
56
Increased cytosolic Ca 2+ stimulates what?
Exocytosis of insulin-containing vesicles
57
What do G proteins bind?
GTP/GDP
58
G proteins are involved in...
Cell signaling
59
What do G proteins undergo in response to protein-protein interactions?
confirmational changes
60
G proteins with GDP bound are...
inactive
61
What helps release GDP?
nucleotide exchange factor
62
What makes the G protein inactive?
GTPases
63
What are the 2 categories of GTPases?
1. Heterotrimeric (alpha/beta/gamma) associated with GPCR
2. Small GTPases
64
Role of alpha s GTPase
stimylates adenylate cyclase (increases cAMP)
65
Role of alpha i GTPase
inhibits adenylate cyclase (decreases cAMP)
66
Role of alpha q GTPase
stimulates phospholipase C (increases IP3/DAG/Ca 2+)
67
Function of Ras (small GTPase)
Regulates cell growth through serine- and threonine- protein kinases
68
Is the trimer in heterotrimeric G proteins active or inactive?
Trimer is inactive
69
What is inactive trimer associated with?
non-stimulated receptor
70
alpha is a GTPase that is inactive with ____, but active with _____
GDP; GTP
71
Alpha is a GTPase that dissociates from ___/____
beta/gamma
72
What does alpha GTPase do?
Alters activities of enzymes and ion channels
73
The active alpha-GTP subunit binds to target protein and...
Changes its activity to increase/decrease a 2nd message
74
What is one way 2nd messengers regulate cellular activity?
By regulating protein kinases that change the activity of specific proteins
75
What are cAMP levels regulated by?
Membrane associated enzymes
76
What converts ATP to cAMP?
Adenylyl cyclase (AC)
77
What targets AC?
Galpha-GTP
78
Galphas-GTP activates ___
G alphai-GTP inhibits ____
AC
79
What does cAMP activate?
Protein Kinase A (PKA)
80
What degrades cAMP to AMP?
cAMP phosphodiesterase
81
List key features of 2nd messenger systems
Specificity
Amplification
Augmentation
Rapid signal termination
82
Specificity
Hormones are specific for cell surface receptors
Different tissues express different enzymes and proteins
83
Amplification
Cascade of enzymes activated by hormone binding signal/receptor that amplifies 1st message by up to 1000-fold
84
Augmentation
Different hormones activate same system
85
Rapid signal termination
Signals inside cell removed by enzymes & transporters
86
Each 2nd messenger system is associated with what?
Specific G alpha subunits and specific protein kinases
87
Different GPCRS interact with what?
Different G-proteins
88
What kind of effects do 2nd messenger systems have?
Acute effects & can regulate gene expression
89
G alpha i inhibits AC, which leads to...
Decrease in cAMP, PKA less active
90
G alpha q stimulates phospholipase C, which leads to...
Increase in IP3, Ca, Protein Kinase C (PKC) activated
91
What is the glucagon receptor expressed in?
Adipose and liver
92
Whaat does the glucagon receptor interact with? What happens?
G alpha s, which when active, stimulates AC and increase in cAMP
93
In adipose, what does glucagon receptor stimulate?
Lipolysis to release fatty acids and glycerol
94
In liver, what does glucagon receptor stimulate?
Pathways that increase glucose output
95
Epinephrin receptor is expressed in what?
Many tissues
96
Epinephrine is known as the...
Acute stress hormone
97
What does epinephrine bind to?ne binds to receptors in the vascular smooth muscle & heart to...
Increase heart rate and BP
98
Epinephrine binds to receptors in the liver to...
Increase glucose output
99
Epinephrine binds to receptors in skeletal muscle to...
Increase ATP production for muscle contraction
100
The insulin receptor is what kind of kinase?
Tyrosine kinase
101
What does insulin binding induce?
Phosphorylation of tyrosine residues on receptor & activates its tyrosine kinase
102
The activated insulin receptor kinase phosphorylates tyrosine residues on ____ ____ _____ and a protein kinase cascade is activated
insulin receptor substrates (IRS)
103
Insulin signaling pathways regulate which 2 things?
1. Fuel metabolism
2. Cell growth
104
MAP kinase stands for what?
Mitogen Activated Protein Kinase
105
3 things associated with metabolic pathways (PI-3K/AKT)
1. Increase GLUT4 trafficking to the cell surface (muscle, adipose)
2. Increase synthesis of glycogen, lipid, & protein
3. Suppress glucose release from liver
106
AKT is what?
A protein kinase
107
What is one way AKT regulates fuel metabolism?
By phosphorylating and activating phosphatase-1
108
What does phosphatase-1 do?
Reverses effects of PKA on lover glucose output
109
How Growth Factor Receptor Tyrosine Kinases Activate Ras G-proteins (3)
1. EGF bindnig stimulates receptor dimerization and autophosphorylation
2. Recruitment of adaptor proteins (Grb2 & Sos) activate Ras
3. Ras-GTP binds to Raf (MAP kinase), initiating MAP kinase cascade
110
What happens if there's mutations in Ras?
GTPase activity abolished
MAP kinase always on
Cell proliferation independent of growth factor
Cancer
111
Epidermal Derived Growth Factor Receptor (EGFR) & Ras are associated with...
Oral cancer & poor prognosis
