2.8: Signaling via Small Molecules Flashcards
state the three mechanisms of small molecule signaling
- independent on plasma membrane proteins
- through ions channels
- downstream of g-protein coupled receptors
give examples of small hydrophobic molecules that can diffuse into the cell
steroid hormones, nitric oxide (NO)
out of the following, list from fastest to slowest diffusion into a cell (without tm channel or receptor): hydrophobic molecules, large uncharged polar molecules, ions, small uncharged polar molecules
hydrophobic molecules, small uncharged polar molecules, large uncharged polar molecules (not super readily by themselves), ions (don’t cross)
ic receptors bind small hydrophobic signaling molecules, what transports them through hydrophilic ec space
carrier proteins
small hydrophobic signaling molecules are released from the carrier and diffuse into target cell, what are they often bound by inside the cell
often bound by nuclear receptor superfamily
t/f all members of nuclear receptor superfamily are in the nucleus
false! they got the name bc everything that they bind eventually end up in the nucleus
describe the structure. of the nuclear super family protein structure (the receptors are specific but structures are common)
- n terminal transcription activating domain activates transcription of target genes
- middle dna-binding domain binds promoters of specific target genes
- c terminal ligand binding domain binds to small hydrophobic signaling molecules
why are orphan nuclear receptors called that
bc they bind to unknown ligand
nuclear receptor superfamily proteins are both the ________ and the _______
receptor and effector
describe how nuclear receptor superfamily proteins act as both the receptor and effector
- ligand binding causes a conformational change in the protein
- dna binding domain (middle section of receptor) is now free to bind promoters of target genes
- inhibitory proteins are released and coactivator proteins are recruited (the cooh on the receptor is like a latch to keep the ligand in)
NO is made from?
arginine
explain the actions of NO
- NO is fast and locally acting due to instability (half life is 5-10 seconds)
- NO can diffuse out of endothelial cells and activate signaling in smooth muscle cells
- acetylcholine activates the receptor on endothelial cells. leads to IP3 and Ca2+ activation to activate NO synthase, arginine is made into NO, there is rapid diffusion of NO across the membrane
- NO binds to guanylyl cyclase in smooth muscle cells to turn GTP to cyclic GMP which leads to rapid relaxation of muslce cells
describe endothelial cells
they are the epithelial cells lining the lumen of BV
state the ligand that activates the receptor on endothelial cells
acetylcholine
state the name of the enzyme that 1. converts arginine into NO
2. that NO binds to to convert gtp to cyclic GMP
- NO synthase
- guanylyl cyclase
where are the following enzymes located
1. NO synthase
2. guanylyl cyclase
- endothelial cells
- smooth muscle cells
state the effect of guanylyl cyclase
rapid relaxation of smooth muscle cells after turning gtp to cyclic gmp
light is not considered a ligand but what can it do
it can initiate signaling events in some cells after affecting a cryptochrome
As part of your CSB498 project, you have replaced the C-terminus of the
nuclear receptor superfamily protein for cortisol with the C-terminus of the
nuclear receptor superfamily protein for vitamin D; what do you expect to
observe in cells that express this chimeric receptor?
a) Cells will activate cortisol responsive genes when exposed to cortisol.
b) Cells will activate cortisol responsive genes when exposed to vitamin D.
c) Cells will activate vitamin D responsive genes when exposed to cortisol.
d) There will be no changes to transcription in response to any signal since
the chimeric nuclear receptor superfamily protein will not bind DNA.
B. B bc of the binding domain and transcription activating domain
A is normal, C is the wrong way
a _________ gradient exists across the plasma membrane
electrochemical
for Na and K ions, which goes more in and which is more out
more K in (higher cytoplasmic [C]) more Na out (higher ec [C])
ion-channel-coupled receptors are _______ by a signaling molecule and are usually closed until a signal is received
gated
describe the events are a ion-channel-coupled receptors are activated
the channels open and mediate passive transport, their ions will flow down their electrochemical gradient
list the 4 ion channels and what is means to be open or closed
- voltage gated: charged AA may move depending on charges of ions of other sides. When closed the ec is + and cytosol is -, when open cytosol is + and ec is -
- ligand gated (ec ligand)
- ligand gated (ic ligand)
- mechanically gated: like a stretch
ion channels are important during ___________ signaling
synaptic
explain how ion channels are important during synaptic signaling, in POV of ion channel
resting synapse:
1. synaptic vesicles of NT are waiting near the PM of the pre-synaptic cell
2. gated ion channels in the target cell are closed
active chemical synapse:
3. a nerve impulse causes NT release by vesicle fusion to the PM
4. NT in the ec space open the ligand gated ion channels in the target cell
5. ions move into the target cell down their [C] gradient, triggering responses in the target cell
