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BIO 317 > 5 - Second Messengers and Effectors Regulate your Metabolism > Flashcards

5 - Second Messengers and Effectors Regulate your Metabolism Flashcards

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1
Q

What are some examples of 2nd messengers and kinase cascades?

A

PLC+PIP2+PKC, cAMP+PKA, and calcium signaling

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2
Q

What are some examples of signal transducers?

A

GPCRs, RTKs, RGCs, gated ion channels, nuclear receptors, and integrins

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3
Q

How do GPCRs work?

A

A ligand binds to a receptor, which activates a G-protein

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4
Q

How do RTKs work?

A

Ligand binding activates tyrosine kinase activity (autophosphorylation)

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5
Q

How do RGCs work?

A

Ligand binding stimulates formation of cGMP from GTP

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6
Q

How do gated ion channels work?

A

Open or close in response to ligand or membrane potential

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7
Q

How do nuclear receptors work?

A

Steroid binding allows the receptor to regulate gene expression

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8
Q

How do integrins work?

A

Binds molecules to ECM, altering interaction with cytoskeleton

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9
Q

What does RTK stand for?

A

Receptor tyrosine kinase

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10
Q

What does RGC stand for?

A

Receptor guanylyl cyclase

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11
Q

How is integration seen in 2nd messenger signaling?

A

Effectors can converge on one part of the cascade

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12
Q

How is divergence seen in 2nd messenger signaling?

A

One effector can affect different proteins in the cascade

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13
Q

What is the purpose of scaffolds?

A

Tether responses together for a rapid and specific response

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14
Q

How do scaffolds increase specificity and speed?

A

All the components in the cascade are localized together (no diffusion needed)

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15
Q

What is a linear signaling pathway?

A

Receptors, transducers, and effectors are in a linear pattern (no crosstalk)

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16
Q

What is a convergent signaling pathway?

A

There is integration between the receptors, transducers, and effectors

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17
Q

What is a divergent signaling pathway?

A

There are multiple impacts to the transducers and/or effectors based on one receptor (or another component)

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18
Q

What is a multiply branched signaling pathway?

A

Lots of crosstalk (convergence, divergence) between the different systems

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19
Q

Which type of signaling pathway most accurately describes the cell?

A

Multiply branched signaling pathway

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20
Q

True or false: effectors cannot affect transducers or receptors

A

False: regulation can occur based on these interactions

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21
Q

How can scaffolds form at a receptor?

A

Scaffold complex, assembly on receptor, and assembly on phosphoinositide docking sites

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22
Q

What does “scaffold complex” refer to (in terms of scaffolds)?

A

A complex can bind to the receptor, having the transducers localized for a specific signaling pathway

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23
Q

What does “assembly on receptor” refer to (in terms of scaffolds)?

A

Once a receptor is activated, soluble proteins can dock on phosphorylation sites, and then transmit downstream signals

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24
Q

What does “assembly on phosphoinositide docking sites” refer to (in terms of scaffolds)?

A

Once a receptor is activated, phosphate groups can be added to phosphoinositides to be used as docking sites for other relay proteins

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25
Q

True or false: there are a large number of extracellular receptor ligands (first messengers)

A

True: there are many different types

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26
Q

True or false: there are a large number of intracellular signaling molecules (second messengers)

A

False: there is only a handful

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27
Q

How many major second messengers are found in animal cells?

A

6

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28
Q

What are the 6 major second messengers found in animal cells?

A

cAMP, cGMP, DAG, IP3, calcium, and phosphoinositides

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29
Q

What does DAG stand for?

A

1,2-diacylglycerol

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30
Q

What does IP3 stand for?

A

Inositol 1,4,5-triphosphate

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31
Q

What are second messengers?

A

Small molecules that diffuse rapidly through the cytoplasm to their protein targets

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32
Q

What is an advantage of a second messenger?

A

Facilitate amplification

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33
Q

True or false: different second messengers have different ranges

A

True: some are short range, while others are long range

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34
Q

True or false: different second messengers have different kinds of outputs

A

True: they can be kinases, ion channels, GPCRs, etc.

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35
Q

How does an amplification cascade work?

A

The number of activated participants increases at each step in the cascade

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36
Q

What is one of the major motifs in cell signaling?

A

Phosphorylation cascade

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37
Q

How does a phosphorylation cascade work?

A

Kinases keep phosphorylating kinases to eventually get to an activate protein

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38
Q

What starts a phosphorylation cascade?

A

Relay molecule

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39
Q

How is a phosphorylation cascade stopped?

A

Through phosphatases (PP)

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40
Q

What do kinases do?

A

Add phosphate groups to proteins

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41
Q

What do phosphatases do?

A

Remove phosphate groups from proteins

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42
Q

True or false: phosphorylation always activates a protein

A

False: phosphorylation can also inactivate a protein (such as glycogen synthase)

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43
Q

What does the speed of the response (generally) depend on?

A

The turnover of the signaling molecule

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44
Q

How fast are phosphorylation cascades?

A

Fast (kinases are already in the cell) (compared to protein synthesis)

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45
Q

How can cells adjust the sensitivity to a signal (5 ways)?

A

Receptor sequestration, receptor down-regulation, receptor inactivation, inactivation of signaling protein, or production of inhibitory protein

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46
Q

What does “receptor sequestration” refer to (in terms of adjusting sensitivity)?

A

Endocytosis of signal, to either stop surface signaling, or start other signaling

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47
Q

What does “receptor down-regulation” refer to (in terms of adjusting sensitivity)?

A

Degrade receptor in a lysosome

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48
Q

What does “receptor inactivation” refer to (in terms of adjusting sensitivity)?

A

Something in the pathway inhibits the receptor

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49
Q

What does “inactivation of signaling protein” refer to (in terms of adjusting sensitivity)?

A

Downstream effects can inhibit the signaling molecule as part of the pathway

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50
Q

What does “production of inhibitory protein” refer to (in terms of adjusting sensitivity)?

A

Can activate an inhibitory protein that inhibits the signaling loop

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51
Q

What is the structure of a fatty acid?

A

Carboxylic acid and a long hydrocarbon chain

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52
Q

Is the carboxylic acid hydrophilic or hydrophobic?

A

Hydrophilic

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53
Q

Is the hydrocarbon chain hydrophilic or hydrophobic?

A

Hydrophobic

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54
Q

How can fatty acids differ?

A

Through length and saturation (bonds between carbons)

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55
Q

What is the structure of a phospholipid?

A

A polar head group, a phosphate group, a glycerol, and 2 fatty acid tails

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56
Q

What are the most common phospholipid head groups?

A

Serine, ethanolamine, choline, and inositol

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57
Q

What is the structure of serine?

A

C(NH3+)(H)(COO-)(CH2)~

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58
Q

What is the structure of ethanolamine?

A

NH3+-CH2-CH2-CH2~

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59
Q

What is the structure of choline?

A

N(CH3)+-CH2-CH2~

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60
Q

What is the structure of inositol?

A

6 carbon ring with hydroxyl groups (similar to a carbohydrate)

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61
Q

What do the different head groups of phospholipids have in common?

A

All very polar

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62
Q

What term describes phospholipids?

A

Amphipathic

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63
Q

What does amphipathic mean?

A

Both hydrophilic and hydrophobic parts of a molecule

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64
Q

What molecule is amphipathic?

A

Phospholipids (both hydrophobic tails and hydrophilic head)

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65
Q

How are phospholipids named?

A

Phosphotidyl[head group]

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66
Q

What do phospholipids make up?

A

Phospholipid bilayer (plasma membrane)

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67
Q

What is the structure of saturated fatty acids?

A

Straight (all single bonds)

68
Q

What is the structure of unsaturated fatty acids?

A

Kink (cis double bond)

69
Q

What is the purpose of unsaturated fatty acids?

A

Allow for fluidity in the plasma membrane

70
Q

What does cholesterol do?

A

Fills gaps between phospholipids for stabilization

71
Q

What is the environment on the outsides of the plasma membrane?

A

Aqueous (hydrophilic)

72
Q

What is the environment on the inside of the plasma membrane?

A

Fatty (hydrophobic)

73
Q

What would happen if the plasma membrane had no unsaturated fatty acids?

A

It would solidify

74
Q

What G-protein subunit activates PLC-beta?

A

aGq

75
Q

What does PLC stand for?

A

Phospholipase-C

76
Q

What activates PLC-beta?

A

aGq

77
Q

What activates PLC-gamma?

A

RTKs

78
Q

What does aGq do?

A

Activates PLC-beta

79
Q

What G-protein is associated with PLC-beta?

A

Gq

80
Q

What does PLC do?

A

Breaks down PIP2 into DAG and IP3

81
Q

What does PI stand for?

A

Phosphatidylinositol

82
Q

What does PI-4 kinase do?

A

Adds a phosphate group to the 4th carbon of PI

83
Q

What is the structure of PI?

A

Phospholipid with head group of inositol

84
Q

What is the structure of PIP?

A

Phospholipid with head group of inositol, and a phosphate on carbon 4

85
Q

What is the end product of PI-4 kinase?

A

PIP

86
Q

What does PIP-5 kinase do?

A

Adds a phosphate group to the 5th carbon of PIP

87
Q

What is the structure of PIP2?

A

Phospholipid with head group of inositol, and a phosphate on carbons 4 and 5

88
Q

What is the end product of PIP-5 kinase?

A

PIP2

89
Q

What bond does PLC break?

A

Bond between the phosphate group and the glycerol in the phospholipid

90
Q

What is the structure of DAG?

A

2 fatty acid tails, glycerol, and a hydroxyl group

91
Q

What is the structure of IP3?

A

Inositol with 3 phosphate groups (on carbon 1, 4, and 5)

92
Q

Where do the phosphate groups come from in IP3?

A

One from phospholipid (connected head group to glycerol), one from PI-4 kinase, and one from PIP-5 kinase

93
Q

Where does DAG go after PLC?

A

Stays membrane bound

94
Q

Where does IP3 go after PLC?

A

Diffuses into the cytosol

95
Q

Why does DAG remain membrane bound?

A

It is lipid soluble (fatty acid tails)

96
Q

Why does IP3 diffuse into the cytosol?

A

It is water soluble (hydroxyl and phosphate groups)

97
Q

How is convergent signaling seen in the PLC pathway?

A

DAG and calcium converge into one signal (PKC)

98
Q

What does PKC stand for?

A

Protein kinase C

99
Q

What is needed to activate PKC?

A

Calcium and DAG

100
Q

What does IP3 do?

A

Binds to IP3-gated calcium ion channels

101
Q

What is the effect of IP3?

A

Release calcium into the cell

102
Q

Where is calcium stored?

A

In the ER lumen

103
Q

What does calcium do (generally)?

A

Function as a 2nd messenger

104
Q

How is IP3 degraded?

A

Phosphatases (IP3->IP2->IP->I)

105
Q

What does calcium do in the PLC pathway?

A

Bind to PKC (along with DAG) to activate it

106
Q

How is the PLC signal turned off?

A

Calcium is pumped back into the ER lumen (ATP pumps), and IP3 is degraded by phosphatases

107
Q

How is PLC-beta activated?

A

GTP hydrolysis from aGq activates PLC-beta

108
Q

True or false: there are many different hormone-induced responses mediated by cAMP

A

True: different cell types have different responses (based on kind of cell)

109
Q

What is the liver response to cAMP?

A

Glycogen breakdown, glucose synthesis, inhibit glycogen synthesis

110
Q

What is glycogen?

A

Storage of glucose monomers

111
Q

What is the skeletal muscle response to cAMP?

A

Glycogen breakdown, inhibit glycogen synthesis

112
Q

What is the thyroid response to cAMP?

A

Secretion of thyroid hormones

113
Q

What is the ovary response to cAMP?

A

Secretion of steroid hormones

114
Q

What does glycogen synthase do?

A

Converts glucose-1-phosphate into glycogen

115
Q

What does glycogen phosphorylase do?

A

Coverts glycogen into glucose-1-phosphate

116
Q

What can glucose-1-phosphate be used for?

A

Glycolysis, or released into the bloodstream

117
Q

True or false: different stimuli acting on the same target cell may induce the same response

A

True: both epinephrine and glucagon lead to the same response in liver cells

118
Q

True or false: both epinephrine and glucagon bind to the same receptor in the cell, thus leading to the same effect

A

False: while they both have the same effect, they bind to different receptors

119
Q

Who discovered glycogenolysis?

A

Krebs and Fischer

120
Q

What is glycogenolysis?

A

A protein phosphorylation cascade that leads to breakdown of glycogen into glucose

121
Q

Why does adrenaline lead to breakdown of glycogen into glucose?

A

Fight-or-flight response (need quick burst of energy)

122
Q

What does cAMP activate in the adrenaline response?

A

PKA

123
Q

What does PKA activate in the adrenaline response?

A

Phosphorylase kinase

124
Q

What does PKA inactivate in the adrenaline response?

A

Glycogen synthase

125
Q

What does phosphorylase kinase activate in the adrenaline response?

A

Glucogen phosphorylase

126
Q

How is glycogen synthase inhibited?

A

Through phosphorylation by PKA

127
Q

What enzyme is inhibited by phosphorylation?

A

Glycogen synthase

128
Q

Why is glycogen synthase inhibited in the adrenaline response?

A

Prevent glucose being converted into glycogen

129
Q

In the adrenaline response, which phosphorylations are inhibitory?

A

PKA -> glycogen synthase

130
Q

In the adrenaline response, which phosphorylations are stimulatory?

A

PKA -> phosphorylase kinase -> glycogen phosphorylase

131
Q

How is convergent signaling seen in the adrenaline response?

A

PKA leads to both activation of glycogen phosphorylase, and inhibition of glycogen synthase, which both converge to increase glucose levels in the cell

132
Q

What is the adrenaline:glucose ratio?

A

1:10^8

133
Q

What does glucagon do?

A

Signals (through cAMP) to break down glycogen into glucose

134
Q

What is glucagon?

A

A hormone that promotes the breakdown of glycogen into glucose

135
Q

What does insulin do?

A

Activates glycogen synthase to store glucose as glycogen

136
Q

If blood sugar levels are high, what hormone is produced?

A

Insulin (promote creation of glycogen)

137
Q

If blood sugar levels are low, what hormone is produced?

A

Glucagon (breaks down glycogen into glucose)

138
Q

If glucagon is released, what is the blood sugar level?

A

Low (needs more glucose)

139
Q

If insulin is released, what is the blood sugar level?

A

High (use up as glycogen)

140
Q

How are blood sugar levels regulated?

A

Integrated signaling between insulin, glucagon, epinephrine, and the glycogen/glucose pathway

141
Q

How does glycogen/glucose levels relate to higher tissues?

A

Can regulate the amount of insulin or glucagon that needs to be released

142
Q

What is the general description of the glycogen/glucose system?

A

Closed, auto-regulatory system

143
Q

What is meant by a “closed, auto-regulatory” system?

A

The system can regulate itself based on the concentrations present (glucose/glycogen)

144
Q

How does PKA regulate gene expression?

A

PKA can also phosphorylate CREB to change receptor levels

145
Q

What is meant by biochemistry “uses groups robustly”?

A

Slight differences in structure significantly change function

146
Q

How does tissue specification relate to cell signaling?

A

Tissues have different AC receptors, how it’s used, and how it’s localized

147
Q

True or false: if there is a mutation in AC, the body cannot produce cAMP

A

False: while that particular tissue may not be able to produce cAMP, other tissues have different ACs that would still be able to produce cAMP

148
Q

What are the differences between the different PKAs and PKCs?

A

What tissues produce them, and where they are localized

149
Q

What is the cell signaling pathway for beta-pancreatic cells in releasing insulin?

A
  1. Glucose is brought into the cell through channels
  2. There is an increase in ATP (glycolysis)
  3. ATP sensitive pumps close, stopping potassium and depolarizing the cell
  4. Calcium channels open as a response to depolarization
  5. Insulin vesicles are released as a response to calcium
150
Q

What is the purposes of having multiple kinases in a phosphorylation cascade?

A

Specificity, amplification, and regulation (can target specific, localized outcomes)

151
Q

How come cAMP from one part of the cell does not impact cAMP-dependent proteins elsewhere?

A

Strong localization of proteins / effects

152
Q

True or false: there can be crosstalk between different receptors

A

True: activated receptors can affect other receptors through direct interactions

153
Q

What is an example of crosstalk between different receptors?

A

Adenosine binding to adenosine receptors changes the affinity of dopamine receptors for dopamine

154
Q

What are some outcomes of receptor crosstalk?

A

Modulation of binding site, modulation of active site, or novel allosteric sites

155
Q

How does evolution relate to cell signaling?

A

Billions of years of evolution lead to the cell signaling pathways seen today

156
Q

What is gluconeogenesis?

A

Production of glucose from non-carbohydrate sources (pyruvate)

157
Q

Where and when does gluconeogenesis occur?

A

Only in liver cells, after glycogen is used up

158
Q

What is glycogenosis?

A

Glucose storage disease

159
Q

Does gluconeogenesis use energy or make energy?

A

Uses energy

160
Q

Does glycogenolysis use energy or make energy?

A

Produces energy

161
Q

What does phosphorylations do for PIs?

A

Create docking sites for other signaling proteins

162
Q

What cells remove the phosphate groups from glucose?

A

Liver cells

163
Q

What enzyme removes the phosphate group from glucose?

A

Glucose-6-phosphatase

164
Q

Why do liver cells remove phosphate groups from glucose?

A

To make it able to leave the cell and go into the bloodstream

165
Q

Why do muscle cells not remove phosphate groups from glucose?

A

To keep the glucose in the cell to be used for its own energy

166
Q

What is required for the direct phosphorylation of PKC?

A

DAG and calcium

167
Q

True or false: aGq activates PI-4 kinase, PIP-5 kinase, and PLC

A

False: aGq only activates PLC

BIO 317 (27 decks)

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