Signaling via small molecules Flashcards
three mechanisms of small molecule signalling
- independent of plasma membrane proteins
- through ion channels
- downstream of G protein coupled receptors
what molecules can diffuse into a cell
small, hydrophobic molecules can diffuse into the cell
hydrophobic moles
diffuse completely
O2, CO2, N2, steroid hormones
small uncharged polar molecules
diffuse a little
H2O, urea, glycerol, NH3
large uncharged polar molecules
diffuse very little
glucose, sucrose, etc
ions
dont diffuse at all
H+, Na+, HCO3-
how do small hydrophobic signalling molecules diffuse into the cell
they are transported by carrier proteins to help them move them through hydrophilic extracellular space
They are released from the carrier and diffuse into target cell
They are often bound by nuclear receptor superfamily proteins within the cell
Nuclear receptor superfamily protein structure
N terminal transcriptional activating domain activates transcription of target genes
The middle DNA binding domain binds promoters of specific target genes
C terminal ligand binding domain binds to hydrophobic signalling molecules
orphan nuclear receptor
binds unknown ligands
how are the nuclear receptor superfamily proteins both receptors and effectors
Ligand binding causes a conformational change in the protein
DNA binding domain is now free to bind promoters of target genes
Inhibitory proteins are released and coactivator proteins are recruited
Nitric oxide
it can rapidly diffuse to signal to nearby cells
its made from arginine
it is fast and locally acting due to instability
it can diffuse out of endothelial cell and activate signaling in smooth muscle cell
what is both the effector and recdeptor for NO
guanylyl cyclase
ion channel coupled receptors
they are gated by a signaling molecule, they are usually closed until a signal is received.
Once open, channels mediate passive transport: ions will flow down their electrochemical gradient
resting synapse
- synaptic vesicles of neurotransmitters are waiting near the plasma membrane of the pre-synaptic cell
- gated ion channels in the target cell are closed
Active chemical synapse
- A nerve impulse causes neurotransmitter release by vesicle fusion to the plasma membrane
- Neurotrasmitters I the extracellular space open the ligand gated ion channels in the target cell
- Ions move into the target cell down their concentration gradient, triggering responses in the target cell
GPCRs
7 transmembrane domain proteins
subunits in GPCRs
G alpha, G beta and G gamme
how does an activated GPCR work
it acts as a GEF to exchange GDP for GTP on the G alpha subunit
GTP bound G alpha is active
Once activated, GTP G alpha dissociates from G beta gamma}Both G alpha and G beta gamma can activate different targets
what does regulator for G protein signalling (RGS) act as
it acts as a GAP to promote GTP hydrolysis by G alpha
what happens to G apha over time
over time GTPase activity of G alpha hydrolyzes GTP to GDP
GDP bound G alpha will re-associate with G game beta
how can different G proteins signal
- some signal through adenlyl cyclase to make cAMP
- some activate phospholipase enzymes to signal through lipids and Ca2+ channels
cAMP
small molecule secondary messenger
cellular concentration of cAMP are usually very low but large amounts are made in response to signals
what is cAMP synthesized from and broken into
it is synthesized from ATP by adenlyl cylase and it is broken down to AMP by cAMP phosphodiesterase
hw does G alpha activate adenlyl cylase
GPCR activates the heterotrimeric
G-protein complex Gs
GTP-bound G⍺ from Gs activates
adenylyl cyclase
adenylyl cyclase converts ATP to
cAMP
