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Biochem > Signal Transduction > Flashcards

Signal Transduction Flashcards

1
Q

List 3 properties of carriers

A
  1. Slow transport rate
  2. Saturable
  3. Active and passive
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2
Q

List 3 properties of channels

A
  1. Very fast transport rate
  2. Not saturable
  3. Passive
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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)

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4
Q

Ca ATPase does what?

A

Pumps Ca 2+ out of cytosol

Across plasma membrane and ER

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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

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6
Q

Ca ATPase is responsible for what?

A

For maintaining low Ca inside the cell (cytosol) and high Ca outside

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7
Q

For Cl, there are high levels _____ and low levels ____ cell

A

outside; inside

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8
Q

When membrane potential becomes more positive, what is it called?

A

Depolarization

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9
Q

When membrane potential becomes more negative, what is it called?

A

Polarization

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10
Q

Impermeant channels generate

A

No electrical potential

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11
Q

Pearmeant channels generate

A

Electrical potential

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12
Q

Cells communicate via what?

A

Chemical messengers

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13
Q

2 examples of ion chemical messengers

A
  1. Blood Ca 2+
  2. Cytosolic Ca 2+
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14
Q

2 functions of ion chemical messengers

A
  1. Ca 2+ homeostasis
  2. 2nd messenger in cytosol
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15
Q

Examples of metabolite chemical messenger

A

Glucose (doesn’t bind to a receptor)

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16
Q

Function of metabolite chemical messenger

A

Insulin release from pancreas

Glycolysis produces ATP which regulates ion channels and insulin release

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17
Q

2 examples of hormone chemical messengers

A
  1. Glucagon
  2. Insulin
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18
Q

Function of hormone chemical messengers

A

Regulate metabolic homeostasis

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19
Q

Example of growth factor chemical messenger

A

Epidermal Growth Factor (associated with oral cancer)

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20
Q

Function of growth factor chemical messenger

A

Stimulates cell growth

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21
Q

Insulin tells our tissues we are _____ _____ ______

A

Fed with glucose

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22
Q

What are signals telling us we aren’t fed?

A

Glucagon and epinephrine

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23
Q

3 fed steps

A
  1. Liver puts out glucose when we’re fasting
  2. Glucagon and epinephrine are signals telling liver to release glucose to blood
  3. Insulin lowers blood glucose by stimulating uptake in adipose and muscle
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24
Q

4 Steps of signal changes by binding to receptors

A
  1. Cells secrete chemical messengers in response to changes in environment
  2. Messenger diffuses/transported through blood
  3. Messenger specifically binds to receptor on target cell (receptor can be in cell/on surface)
  4. Binding to receptor elicits cellular response
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25
Q

Chemical messengers that bind to cell surface receptors generate what?

A

2nd messenger inside cell

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26
Q

1st message

A

Chemical messenger binds to cell surface receptor

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27
Q

2nd message

A

Generated in response to 1st messenger binding to cell surface receptor

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28
Q

What do changes in 2nd messenger levels cause?

A

Changes in protein activity in cell?

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29
Q

Are 2nd messenger in cell present in high or low levels?

A

Low

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30
Q

Why are 2nd messengers present in low levels?

A

So small changes can have big effect

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31
Q

List 3 classes of cell surface receptors

A
  1. Ion channels
  2. Tyrosine kinase receptors
  3. G-protein coupled receptors
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32
Q

Examples of ion channels

A
  1. cytosolic Ca 2+, membrane potential
  2. insulin release
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33
Q

Examples of tyrosine kinase receptors

A
  1. insulin
  2. Epidermal growth factor (EGF)
  3. GH, PRL, associated JAK kinases
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34
Q

Examples of G-protein coupled receptors

A
  1. Epinephrine, glucagon
  2. cAMP, IP3/DAG/Ca 2+
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35
Q

Energy consuming processes pump Ca ____ _____ ____ against a large unfavourable gradient for Ca 2+

A

out of cytosol

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36
Q

What is gradient for Ca 2+ to enter cytosol?

A

~10 000 to 1

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37
Q

Ca 2+ channels allow Ca 2+ ions to diffuse through cell membrane….

A

Down its electrochemical gradient

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38
Q

Ca 2+ channel 4 steps

A
  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
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39
Q

Ca 2+ channels _____ regulate cytosolic Ca 2+

A

directly

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40
Q

Potassium channels _____ regulate cytosolic Ca 2+ by changing Vm

A

indirectly

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41
Q

Active/open K channels _______ Vm, causing Cav to _____. Less Ca 2+ enters cytosol

A

polarize (bc K going out); close

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42
Q

Inactive/closed K channels ______ Vm, causing Cav to ______. More Ca 2+ enters cytosol

A

depolarize (lots of K in); open

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43
Q

ATP gated K channels couple high blood glucose to…

A

Insulin release in pancreatic beta cells

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44
Q

When are Katp channels open/active?

A

When ATP in cell is low bc polarized Vm, less Ca 2+ enters cytosol

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45
Q

When are Katp channels closed/inactive?

A

When ATP in cell is high bc depolarized Vm, more Ca 2+ enters cytosol

46
Q

What stimulates insulin release?

A

Cytosolic Ca 2+

47
Q

What inhibits the ATP-gated K channel, depolarizing Vm?

A

ATP

48
Q

ATP increases in response to what?

A

Increased glucose

49
Q

High ATP -> membrane _____

A

Depolarized

50
Q

Low ATP -> membrane _____

A

Polarized

51
Q

Ion channels couple glucose catabolism and ATP to…

A

Insulin release from pancreatic beta cells

52
Q

How does glucose enter beta cells?

A

Through GLUT2 transporter

53
Q

Which channels does ATP generated from catabolism close?

A

Katp channels

54
Q

Reduced K+ efflux -> _______ membrane

A

depolarizes

55
Q

What opens Cav?

A

Depolarization

56
Q

Increased cytosolic Ca 2+ stimulates what?

A

Exocytosis of insulin-containing vesicles

57
Q

What do G proteins bind?

A

GTP/GDP

58
Q

G proteins are involved in…

A

Cell signaling

59
Q

What do G proteins undergo in response to protein-protein interactions?

A

confirmational changes

60
Q

G proteins with GDP bound are…

A

inactive

61
Q

What helps release GDP?

A

nucleotide exchange factor

62
Q

What makes the G protein inactive?

A

GTPases

63
Q

What are the 2 categories of GTPases?

A
  1. Heterotrimeric (alpha/beta/gamma) associated with GPCR
  2. Small GTPases
64
Q

Role of alpha s GTPase

A

stimylates adenylate cyclase (increases cAMP)

65
Q

Role of alpha i GTPase

A

inhibits adenylate cyclase (decreases cAMP)

66
Q

Role of alpha q GTPase

A

stimulates phospholipase C (increases IP3/DAG/Ca 2+)

67
Q

Function of Ras (small GTPase)

A

Regulates cell growth through serine- and threonine- protein kinases

68
Q

Is the trimer in heterotrimeric G proteins active or inactive?

A

Trimer is inactive

69
Q

What is inactive trimer associated with?

A

non-stimulated receptor

70
Q

alpha is a GTPase that is inactive with ____, but active with _____

A

GDP; GTP

71
Q

Alpha is a GTPase that dissociates from ___/____

A

beta/gamma

72
Q

What does alpha GTPase do?

A

Alters activities of enzymes and ion channels

73
Q

The active alpha-GTP subunit binds to target protein and…

A

Changes its activity to increase/decrease a 2nd message

74
Q

What is one way 2nd messengers regulate cellular activity?

A

By regulating protein kinases that change the activity of specific proteins

75
Q

What are cAMP levels regulated by?

A

Membrane associated enzymes

76
Q

What converts ATP to cAMP?

A

Adenylyl cyclase (AC)

77
Q

What targets AC?

A

Galpha-GTP

78
Q

Galphas-GTP activates ___
G alphai-GTP inhibits ____

A

AC

79
Q

What does cAMP activate?

A

Protein Kinase A (PKA)

80
Q

What degrades cAMP to AMP?

A

cAMP phosphodiesterase

81
Q

List key features of 2nd messenger systems

A

Specificity
Amplification
Augmentation
Rapid signal termination

82
Q

Specificity

A

Hormones are specific for cell surface receptors
Different tissues express different enzymes and proteins

83
Q

Amplification

A

Cascade of enzymes activated by hormone binding signal/receptor that amplifies 1st message by up to 1000-fold

84
Q

Augmentation

A

Different hormones activate same system

85
Q

Rapid signal termination

A

Signals inside cell removed by enzymes & transporters

86
Q

Each 2nd messenger system is associated with what?

A

Specific G alpha subunits and specific protein kinases

87
Q

Different GPCRS interact with what?

A

Different G-proteins

88
Q

What kind of effects do 2nd messenger systems have?

A

Acute effects & can regulate gene expression

89
Q

G alpha i inhibits AC, which leads to…

A

Decrease in cAMP, PKA less active

90
Q

G alpha q stimulates phospholipase C, which leads to…

A

Increase in IP3, Ca, Protein Kinase C (PKC) activated

91
Q

What is the glucagon receptor expressed in?

A

Adipose and liver

92
Q

Whaat does the glucagon receptor interact with? What happens?

A

G alpha s, which when active, stimulates AC and increase in cAMP

93
Q

In adipose, what does glucagon receptor stimulate?

A

Lipolysis to release fatty acids and glycerol

94
Q

In liver, what does glucagon receptor stimulate?

A

Pathways that increase glucose output

95
Q

Epinephrin receptor is expressed in what?

A

Many tissues

96
Q

Epinephrine is known as the…

A

Acute stress hormone

97
Q

What does epinephrine bind to?ne binds to receptors in the vascular smooth muscle & heart to…

A

Increase heart rate and BP

98
Q

Epinephrine binds to receptors in the liver to…

A

Increase glucose output

99
Q

Epinephrine binds to receptors in skeletal muscle to…

A

Increase ATP production for muscle contraction

100
Q

The insulin receptor is what kind of kinase?

A

Tyrosine kinase

101
Q

What does insulin binding induce?

A

Phosphorylation of tyrosine residues on receptor & activates its tyrosine kinase

102
Q

The activated insulin receptor kinase phosphorylates tyrosine residues on ____ ____ _____ and a protein kinase cascade is activated

A

insulin receptor substrates (IRS)

103
Q

Insulin signaling pathways regulate which 2 things?

A
  1. Fuel metabolism
  2. Cell growth
104
Q

MAP kinase stands for what?

A

Mitogen Activated Protein Kinase

105
Q

3 things associated with metabolic pathways (PI-3K/AKT)

A
  1. Increase GLUT4 trafficking to the cell surface (muscle, adipose)
  2. Increase synthesis of glycogen, lipid, & protein
  3. Suppress glucose release from liver
106
Q

AKT is what?

A

A protein kinase

107
Q

What is one way AKT regulates fuel metabolism?

A

By phosphorylating and activating phosphatase-1

108
Q

What does phosphatase-1 do?

A

Reverses effects of PKA on lover glucose output

109
Q

How Growth Factor Receptor Tyrosine Kinases Activate Ras G-proteins (3)

A
  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
Q

What happens if there’s mutations in Ras?

A

GTPase activity abolished

MAP kinase always on

Cell proliferation independent of growth factor

Cancer

111
Q

Epidermal Derived Growth Factor Receptor (EGFR) & Ras are associated with…

A

Oral cancer & poor prognosis

Biochem (6 decks)

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