5 - Second Messengers and Effectors Regulate your Metabolism Flashcards
1
Q
What are some examples of 2nd messengers and kinase cascades?
A
PLC+PIP2+PKC, cAMP+PKA, and calcium signaling
2
Q
What are some examples of signal transducers?
A
GPCRs, RTKs, RGCs, gated ion channels, nuclear receptors, and integrins
3
Q
How do GPCRs work?
A
A ligand binds to a receptor, which activates a G-protein
4
Q
How do RTKs work?
A
Ligand binding activates tyrosine kinase activity (autophosphorylation)
5
Q
How do RGCs work?
A
Ligand binding stimulates formation of cGMP from GTP
6
Q
How do gated ion channels work?
A
Open or close in response to ligand or membrane potential
7
Q
How do nuclear receptors work?
A
Steroid binding allows the receptor to regulate gene expression
8
Q
How do integrins work?
A
Binds molecules to ECM, altering interaction with cytoskeleton
9
Q
What does RTK stand for?
A
Receptor tyrosine kinase
10
Q
What does RGC stand for?
A
Receptor guanylyl cyclase
11
Q
How is integration seen in 2nd messenger signaling?
A
Effectors can converge on one part of the cascade
12
Q
How is divergence seen in 2nd messenger signaling?
A
One effector can affect different proteins in the cascade
13
Q
What is the purpose of scaffolds?
A
Tether responses together for a rapid and specific response
14
Q
How do scaffolds increase specificity and speed?
A
All the components in the cascade are localized together (no diffusion needed)
15
Q
What is a linear signaling pathway?
A
Receptors, transducers, and effectors are in a linear pattern (no crosstalk)
16
Q
What is a convergent signaling pathway?
A
There is integration between the receptors, transducers, and effectors
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)
18
Q
What is a multiply branched signaling pathway?
A
Lots of crosstalk (convergence, divergence) between the different systems
19
Q
Which type of signaling pathway most accurately describes the cell?
A
Multiply branched signaling pathway
20
Q
True or false: effectors cannot affect transducers or receptors
A
False: regulation can occur based on these interactions
21
Q
How can scaffolds form at a receptor?
A
Scaffold complex, assembly on receptor, and assembly on phosphoinositide docking sites
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
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
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
25
True or false: there are a large number of extracellular receptor ligands (first messengers)
True: there are many different types
26
True or false: there are a large number of intracellular signaling molecules (second messengers)
False: there is only a handful
27
How many major second messengers are found in animal cells?
6
28
What are the 6 major second messengers found in animal cells?
cAMP, cGMP, DAG, IP3, calcium, and phosphoinositides
29
What does DAG stand for?
1,2-diacylglycerol
30
What does IP3 stand for?
Inositol 1,4,5-triphosphate
31
What are second messengers?
Small molecules that diffuse rapidly through the cytoplasm to their protein targets
32
What is an advantage of a second messenger?
Facilitate amplification
33
True or false: different second messengers have different ranges
True: some are short range, while others are long range
34
True or false: different second messengers have different kinds of outputs
True: they can be kinases, ion channels, GPCRs, etc.
35
How does an amplification cascade work?
The number of activated participants increases at each step in the cascade
36
What is one of the major motifs in cell signaling?
Phosphorylation cascade
37
How does a phosphorylation cascade work?
Kinases keep phosphorylating kinases to eventually get to an activate protein
38
What starts a phosphorylation cascade?
Relay molecule
39
How is a phosphorylation cascade stopped?
Through phosphatases (PP)
40
What do kinases do?
Add phosphate groups to proteins
41
What do phosphatases do?
Remove phosphate groups from proteins
42
True or false: phosphorylation always activates a protein
False: phosphorylation can also inactivate a protein (such as glycogen synthase)
43
What does the speed of the response (generally) depend on?
The turnover of the signaling molecule
44
How fast are phosphorylation cascades?
Fast (kinases are already in the cell) (compared to protein synthesis)
45
How can cells adjust the sensitivity to a signal (5 ways)?
Receptor sequestration, receptor down-regulation, receptor inactivation, inactivation of signaling protein, or production of inhibitory protein
46
What does "receptor sequestration" refer to (in terms of adjusting sensitivity)?
Endocytosis of signal, to either stop surface signaling, or start other signaling
47
What does "receptor down-regulation" refer to (in terms of adjusting sensitivity)?
Degrade receptor in a lysosome
48
What does "receptor inactivation" refer to (in terms of adjusting sensitivity)?
Something in the pathway inhibits the receptor
49
What does "inactivation of signaling protein" refer to (in terms of adjusting sensitivity)?
Downstream effects can inhibit the signaling molecule as part of the pathway
50
What does "production of inhibitory protein" refer to (in terms of adjusting sensitivity)?
Can activate an inhibitory protein that inhibits the signaling loop
51
What is the structure of a fatty acid?
Carboxylic acid and a long hydrocarbon chain
52
Is the carboxylic acid hydrophilic or hydrophobic?
Hydrophilic
53
Is the hydrocarbon chain hydrophilic or hydrophobic?
Hydrophobic
54
How can fatty acids differ?
Through length and saturation (bonds between carbons)
55
What is the structure of a phospholipid?
A polar head group, a phosphate group, a glycerol, and 2 fatty acid tails
56
What are the most common phospholipid head groups?
Serine, ethanolamine, choline, and inositol
57
What is the structure of serine?
C(NH3+)(H)(COO-)(CH2)~
58
What is the structure of ethanolamine?
NH3+-CH2-CH2-CH2~
59
What is the structure of choline?
N(CH3)+-CH2-CH2~
60
What is the structure of inositol?
6 carbon ring with hydroxyl groups (similar to a carbohydrate)
61
What do the different head groups of phospholipids have in common?
All very polar
62
What term describes phospholipids?
Amphipathic
63
What does amphipathic mean?
Both hydrophilic and hydrophobic parts of a molecule
64
What molecule is amphipathic?
Phospholipids (both hydrophobic tails and hydrophilic head)
65
How are phospholipids named?
Phosphotidyl[head group]
66
What do phospholipids make up?
Phospholipid bilayer (plasma membrane)
67
What is the structure of saturated fatty acids?
Straight (all single bonds)
68
What is the structure of unsaturated fatty acids?
Kink (cis double bond)
69
What is the purpose of unsaturated fatty acids?
Allow for fluidity in the plasma membrane
70
What does cholesterol do?
Fills gaps between phospholipids for stabilization
71
What is the environment on the outsides of the plasma membrane?
Aqueous (hydrophilic)
72
What is the environment on the inside of the plasma membrane?
Fatty (hydrophobic)
73
What would happen if the plasma membrane had no unsaturated fatty acids?
It would solidify
74
What G-protein subunit activates PLC-beta?
aGq
75
What does PLC stand for?
Phospholipase-C
76
What activates PLC-beta?
aGq
77
What activates PLC-gamma?
RTKs
78
What does aGq do?
Activates PLC-beta
79
What G-protein is associated with PLC-beta?
Gq
80
What does PLC do?
Breaks down PIP2 into DAG and IP3
81
What does PI stand for?
Phosphatidylinositol
82
What does PI-4 kinase do?
Adds a phosphate group to the 4th carbon of PI
83
What is the structure of PI?
Phospholipid with head group of inositol
84
What is the structure of PIP?
Phospholipid with head group of inositol, and a phosphate on carbon 4
85
What is the end product of PI-4 kinase?
PIP
86
What does PIP-5 kinase do?
Adds a phosphate group to the 5th carbon of PIP
87
What is the structure of PIP2?
Phospholipid with head group of inositol, and a phosphate on carbons 4 and 5
88
What is the end product of PIP-5 kinase?
PIP2
89
What bond does PLC break?
Bond between the phosphate group and the glycerol in the phospholipid
90
What is the structure of DAG?
2 fatty acid tails, glycerol, and a hydroxyl group
91
What is the structure of IP3?
Inositol with 3 phosphate groups (on carbon 1, 4, and 5)
92
Where do the phosphate groups come from in IP3?
One from phospholipid (connected head group to glycerol), one from PI-4 kinase, and one from PIP-5 kinase
93
Where does DAG go after PLC?
Stays membrane bound
94
Where does IP3 go after PLC?
Diffuses into the cytosol
95
Why does DAG remain membrane bound?
It is lipid soluble (fatty acid tails)
96
Why does IP3 diffuse into the cytosol?
It is water soluble (hydroxyl and phosphate groups)
97
How is convergent signaling seen in the PLC pathway?
DAG and calcium converge into one signal (PKC)
98
What does PKC stand for?
Protein kinase C
99
What is needed to activate PKC?
Calcium and DAG
100
What does IP3 do?
Binds to IP3-gated calcium ion channels
101
What is the effect of IP3?
Release calcium into the cell
102
Where is calcium stored?
In the ER lumen
103
What does calcium do (generally)?
Function as a 2nd messenger
104
How is IP3 degraded?
Phosphatases (IP3->IP2->IP->I)
105
What does calcium do in the PLC pathway?
Bind to PKC (along with DAG) to activate it
106
How is the PLC signal turned off?
Calcium is pumped back into the ER lumen (ATP pumps), and IP3 is degraded by phosphatases
107
How is PLC-beta activated?
GTP hydrolysis from aGq activates PLC-beta
108
True or false: there are many different hormone-induced responses mediated by cAMP
True: different cell types have different responses (based on kind of cell)
109
What is the liver response to cAMP?
Glycogen breakdown, glucose synthesis, inhibit glycogen synthesis
110
What is glycogen?
Storage of glucose monomers
111
What is the skeletal muscle response to cAMP?
Glycogen breakdown, inhibit glycogen synthesis
112
What is the thyroid response to cAMP?
Secretion of thyroid hormones
113
What is the ovary response to cAMP?
Secretion of steroid hormones
114
What does glycogen synthase do?
Converts glucose-1-phosphate into glycogen
115
What does glycogen phosphorylase do?
Coverts glycogen into glucose-1-phosphate
116
What can glucose-1-phosphate be used for?
Glycolysis, or released into the bloodstream
117
True or false: different stimuli acting on the same target cell may induce the same response
True: both epinephrine and glucagon lead to the same response in liver cells
118
True or false: both epinephrine and glucagon bind to the same receptor in the cell, thus leading to the same effect
False: while they both have the same effect, they bind to different receptors
119
Who discovered glycogenolysis?
Krebs and Fischer
120
What is glycogenolysis?
A protein phosphorylation cascade that leads to breakdown of glycogen into glucose
121
Why does adrenaline lead to breakdown of glycogen into glucose?
Fight-or-flight response (need quick burst of energy)
122
What does cAMP activate in the adrenaline response?
PKA
123
What does PKA activate in the adrenaline response?
Phosphorylase kinase
124
What does PKA inactivate in the adrenaline response?
Glycogen synthase
125
What does phosphorylase kinase activate in the adrenaline response?
Glucogen phosphorylase
126
How is glycogen synthase inhibited?
Through phosphorylation by PKA
127
What enzyme is inhibited by phosphorylation?
Glycogen synthase
128
Why is glycogen synthase inhibited in the adrenaline response?
Prevent glucose being converted into glycogen
129
In the adrenaline response, which phosphorylations are inhibitory?
PKA -> glycogen synthase
130
In the adrenaline response, which phosphorylations are stimulatory?
PKA -> phosphorylase kinase -> glycogen phosphorylase
131
How is convergent signaling seen in the adrenaline response?
PKA leads to both activation of glycogen phosphorylase, and inhibition of glycogen synthase, which both converge to increase glucose levels in the cell
132
What is the adrenaline:glucose ratio?
1:10^8
133
What does glucagon do?
Signals (through cAMP) to break down glycogen into glucose
134
What is glucagon?
A hormone that promotes the breakdown of glycogen into glucose
135
What does insulin do?
Activates glycogen synthase to store glucose as glycogen
136
If blood sugar levels are high, what hormone is produced?
Insulin (promote creation of glycogen)
137
If blood sugar levels are low, what hormone is produced?
Glucagon (breaks down glycogen into glucose)
138
If glucagon is released, what is the blood sugar level?
Low (needs more glucose)
139
If insulin is released, what is the blood sugar level?
High (use up as glycogen)
140
How are blood sugar levels regulated?
Integrated signaling between insulin, glucagon, epinephrine, and the glycogen/glucose pathway
141
How does glycogen/glucose levels relate to higher tissues?
Can regulate the amount of insulin or glucagon that needs to be released
142
What is the general description of the glycogen/glucose system?
Closed, auto-regulatory system
143
What is meant by a "closed, auto-regulatory" system?
The system can regulate itself based on the concentrations present (glucose/glycogen)
144
How does PKA regulate gene expression?
PKA can also phosphorylate CREB to change receptor levels
145
What is meant by biochemistry "uses groups robustly"?
Slight differences in structure significantly change function
146
How does tissue specification relate to cell signaling?
Tissues have different AC receptors, how it's used, and how it's localized
147
True or false: if there is a mutation in AC, the body cannot produce cAMP
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
What are the differences between the different PKAs and PKCs?
What tissues produce them, and where they are localized
149
What is the cell signaling pathway for beta-pancreatic cells in releasing insulin?
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
What is the purposes of having multiple kinases in a phosphorylation cascade?
Specificity, amplification, and regulation (can target specific, localized outcomes)
151
How come cAMP from one part of the cell does not impact cAMP-dependent proteins elsewhere?
Strong localization of proteins / effects
152
True or false: there can be crosstalk between different receptors
True: activated receptors can affect other receptors through direct interactions
153
What is an example of crosstalk between different receptors?
Adenosine binding to adenosine receptors changes the affinity of dopamine receptors for dopamine
154
What are some outcomes of receptor crosstalk?
Modulation of binding site, modulation of active site, or novel allosteric sites
155
How does evolution relate to cell signaling?
Billions of years of evolution lead to the cell signaling pathways seen today
156
What is gluconeogenesis?
Production of glucose from non-carbohydrate sources (pyruvate)
157
Where and when does gluconeogenesis occur?
Only in liver cells, after glycogen is used up
158
What is glycogenosis?
Glucose storage disease
159
Does gluconeogenesis use energy or make energy?
Uses energy
160
Does glycogenolysis use energy or make energy?
Produces energy
161
What does phosphorylations do for PIs?
Create docking sites for other signaling proteins
162
What cells remove the phosphate groups from glucose?
Liver cells
163
What enzyme removes the phosphate group from glucose?
Glucose-6-phosphatase
164
Why do liver cells remove phosphate groups from glucose?
To make it able to leave the cell and go into the bloodstream
165
Why do muscle cells not remove phosphate groups from glucose?
To keep the glucose in the cell to be used for its own energy
166
What is required for the direct phosphorylation of PKC?
DAG and calcium
167
True or false: aGq activates PI-4 kinase, PIP-5 kinase, and PLC
False: aGq only activates PLC
