adenylate cyclase :epinephrine and glucagon Flashcards
AC
looking at this pathway from the POV of epinephrine…
Heterotrimeric G proteins
labeled as G_s, because they are stimulatory pathways… they are called as such because there are 3 SU and are trimeric… G referring to binding GTP/GDP. This G has nOTHING to do with GL/Gm subunits in PP1c. They are anchored to the membrane by fatty acid side chains.
Norepinephrine has similar receptor
Differential affinity
being bound to one thing vs another, there is a difference in binding affinity/characteristics of binding
In this case, ligand-receptor complex vs AC.
Initially we have receptor and G complex, no hormones in receptors. Hormone comes along and binds (epinephrine or nor, or glucagon, insulin uses diff pathway). Now receptor is occupied, causes displaces of GDP that was bound to alpha subunit, swaps it for a GTP. All written as G_s due to it being a stimulating pathway. When swapping occurs, G_s moves to AC and activates it.
When together, AC and GTP, AC is taking atp and converting it to cAMP which is the cAMP that activates PKA to do bicyclic cascade event… SO all cAMP we have talked about it coming from here!!!!
At some point cAMP needs to be destroyed, there is a specific phosphodiesterase that will destroy cAMP and converts to AMP. This will reverse the action of PKA, bc needs cAMP to be active.
TIMING IS BASED ON GDP TO GTP AND HOW LONG BEFORE PHOSPHODIESTERASE IS OUTPACING PRODUCTION OF CAMP
caffeine
inhibits phosphodiesterase, which means cAMP is continusously active, so if it falls off, nothing to destroy it and will rebind. If constantly turned on, constantly breaking down glycogen store, so there is always sugar in the blood.
Connection between caffeine and sleep: brain looks for adenosine as a “sleep signal” , caffine looks like adenosine, acts like a CI and brain does not register the concentration of adenosine. so you build up a ton of adenosine when on caffeine and have a “crash” after.
