Endocrinology | Receptor Pathways

iron in generics what we're going to do in this video is we're going to talk about the various different types of receptor pathways now to go over every single type of receptor for every single hormone it's just it's impossible to do all of that in this video so what we're going to do is we're going to focus on the most important receptor pathways okay now before I do that let me explain something because we can't just dive right into these pathways and not explain why we're doing them so hormones there's two different types of hormones right so we can really define hormones two different ways we can say some are actually going to be peptide hormones right or some are actually going to be steroid hormones now why am I telling you that because peptide hormones are what we refer to as water soluble meaning that if you put these proteins into water it'll actually be able to have its hydrophilic amino acid to interact with the water it'll be soluble in the water all right it will precipitate okay so in other words we can say that peptide hormones are what's called water soluble but here's the problem if you look at an actual cells let's say I draw a cell here let's say here's just a general cell right so look at this guy's he's ready to be stimulated now here's the problem let's say I draw here in blue a peptide hormone now a peptide hormone the problem with peptide hormones is that they can have charges and they're pretty big - so they can't just fit through this cell membrane why one reason is because it's too big the second reason is because the membrane is actually made up of phospholipid so if it's lipid salt if this this actual membrane is a phospholipid bilayer a protein can't move through it right so it's because it's not going to be soluble within the lipid it's water soluble so in other words this protein can't penetrate through the cell so the only way that this protein this hormone can exert its effects on this cell is it has to do it on a certain type of receptor there has to be a receptor on the membrane that this hormone combined on two and then in this cell there's actually going to be these messengers that can say signals all throughout the cell to perform the action of this hormone now these messages that are occurring inside of the cell from an extra cellular membrane receptor is going to be through what's called second messenger systems so these peptide hormones are going to work through what's called the second messenger systems right we're only going to focus on two significant ones okay one we're going to talk about the GQ pathway and one will talk about the G stimulatory pathway okay and we might even discuss a little bit about the G inhibitory pathway but in other words we're talking about the second messenger systems and how these hormones are working on these receptors and in mediating these intracellular responses okay now with scare roid hormones they're a little bit different steroid hormones are lipid soluble and the reason why is they're derived from cholesterol okay so because the derived from cholesterol their lipid soluble meaning that they don't have to have a receptor on the outside of the cell they can have receptors present inside the cell why because let's say that this is your lipid hormone right here if he's a lipid hormone or a steroid based hormone he's lipid soluble right he can pass right through the lipid bilayer and come and bind onto a receptor inside the cell so we're going to focus on just a generic pathway for steroid hormones and how they exert their effects now now that we've done that let's go ahead and just list a couple peptide hormones on a couple steroid hormones that way we know and I'm just giving you a couple we could stay here for peptide hormones I could be mentioning FSH I could mention LH I can mention growth hormone I could mention glucagon I could mention parathyroid hormone and insulin and the list could go on and on and on oxytocin ADH but the basic idea is to know that these peptide hormones are going to be working through the second messenger systems and I'll explain what I mean by that where steroid hormones we're going to take for example the classics testosterone estrogen progesterone aldosterone cortisol go Natick or dacoits and so on and so forth okay going addict or turquoise we could keep listing these we could even say vitamin D and we could even say thyroxine acts like a steroid hormone but you get the basic point these guys have to have receptors inside the cell these guys have to have receptors on the cell membrane so now that we know that let's go ahead and dig in here so what I did is I kind of blew out a really big cell and what we're going to do is we're going to take it to look at two of these receptor pathways right here okay so let's go ahead and do that let's say we focus first on this red receptor now these red receptors that I'm drawing drawing here it's actually coupled with what's called a g-protein so inside of the cell I have what's called a g-protein so these are called g-protein coupled receptors okay so this is called a g-protein coupled receptor now a little bit about their structure protein lines if you notice I drew a line here it's passing through the membrane seven times watch one two three four five six seven so they call these seven pass receptors seven pass trans transmembrane receptors or serpentine receptors now let's say for this specific g-protein this specific one we're going to take a look at what's called G stimulatory so G stimulatory protein so here's our G stimulatory protein so now what's going to activate this G stimulatory protein so let's say I have a hormone here a peptide hormone let's say for example I just picked by random epinephrine okay here's my epinephrine an epinephrine binds on to this receptor when he binds on to this receptor what it does is it changes the overall three-dimensional structure of the inside portion of the receptor and activates this G's taury protein what's this G stimulatory protein normally bound to okay normally this G stimulatory protein is bound to what's called GDP so normally it's bound to what's called g.d.p but when epinephrine acts on this receptor and changes the overall three-dimensional structure this receptor activates this G stimulatory protein and it displaces the gdp and adds on gtp so now look we're binding on we're binding onto this gtp and what do we do we get rid of the G DP okay so now GDP is actually gonna be gone so let's show that here so look now look what it looks like after this so this G stimulatory protein actually can move it's a peripheral membrane protein right so now look at it here he is right here G's stimulatory proteins activated why is he activated because he's bound to gtp so we can show here bound to him is G TP he's bound to him that he's activating this guy now what is this G stimulatory protein due he goes to this effector enzyme that's present on the cell membrane okay so let's draw here in effector enzyme so let's draw this nice little effector in boy this guy has a specific point of an attachment for that G stimulatory protein so G stimulatory protein is going to come in and it's going to perfectly attached to this enzyme right here so look at it comes in in and attaches to this enzyme when it attaches to this enzyme this enzyme becomes very very active so share the gtp here gtp is still bound to the G stimulatory protein this enzyme becomes super active what's this enzyme here called this enzyme is called adenylate cyclase what adenylate cyclase does is it has a specific enzyme look at this it has an enzyme and this enzyme has like a cutting portion here look at this he's got the teeth right there like a look his legs have teeth so his legs have teeth so what's going to happen this enzyme right here is actually going to cut the GTP so what does this enzyme here call it it's called a gtp ace so when it cuts the gtp what does it do it converts gtp into GDP what was gdp doing to the g-protein it was keeping it off it was the off switch what was gtp doing to this it was the on switch it was turning this guy on well before it was on now what when the dis gtp a cuts that phosphate so what is he ripping out of there he's ripping out of this a phosphate he turns off this G symmetry protein because now this is no longer gtp bound it's actually GDP look at that now what happens from him cutting that gtp into GDP he then uses that energy to convert a very important molecule which we know a tipi he converts that into cyclic a and P okay so then he converts it into cyclic AMP e then cyclic a.m. peak that's what he does he comes and he activates a very specific enzyme so let's say that this is this enzyme right here and we're going to draw this one in green this enzyme is actually going to be a protein kinase so here's our protein kinase what is cyclic a and P do cyclic a and P comes over and activates this protein kinase is it doesn't have to just be one it can activate multiple protein kinases and then guess what these protein kindnesses are going to go and do this is where it can go and do a ton of different thing here here's what you need to remember what's the definition of a kinase a kinase by definition is something that phosphorylates right so it's a good phosphorylation so phosphorylation of proteins and enzymes and different types of substances right so what is this protein kinase a going to do he's going to go and phosphorylate tons of different proteins and enzymes so let's show that here so in cyclic ANP acts on him he becomes active because previously he was inactive but when cyclic A&P acts on him he becomes very active and look what he can go and do he can go and do what's called phosphorylation of various proteins proteins right so in fact if it phosphorylates various different types of types of proteins what can those proteins do it depends on what the protein is for example let's say that one of the proteins is embedded here in the membrane let's say this is this protein right here and this protein will only open this channel so let's say it's a channel protein and this channel protein is normally closed in this cell but then this protein kinase a he comes over here and he puts a phosphate group onto that protein and then the protein channel opens and then certain types of ions can flow in for example maybe it could be for calcium maybe it could be for sodium whoever knows but it could be causing ions to flow in or flow out so it doesn't just have to be for ions coming in it could be for ions to go out it just all depends on the cell right generally they're going to be having cations coming into the cell but in general just know that this phosphorylation could do what it could change the membrane permeability of certain ions you know it could also activate a different a lot of different enzymes let's say that you're trying to do glycolysis in the cell so you're trying to convert glucose into pyruvate well you know there's a lot of different enzymes that regulate these metabolic pathways guess what this far that guess what this protein can do he can come over and you can put a phosphate on these enzymes so he can regulate metabolic pathways he can regulate the membrane permeability tons of different things guess what else he could do you know there's also proteins over here that really really are important for being able to control transcription and a lot of different other properties guess what this guy can do he can come over here and he can do phosphorylation of this this transcription factor let's call this a transcription factor T F and guess what that could do that could come into this actual cell activate these genes and make new proteins so it can actually cause new proteins who knows it might even cause the cell to proliferate too so it could even cause cell growth so it can cause cell growth tons of different effects so if you see here now this one mon can act on this cell and produce a plethora of effects it just depends on what the cells function is I just want you to get the basic idea here that what can protein kinase they do he can phosphorylate various different types of proteins what are those proteins it depends if it's metabolic it can maybe regulate certain types of enzymes and glycolysis or gluconeogenesis or glycogen metabolism who knows it can phosphorylate proteins for membrane channels to change the ion permeability and can phosphorylate different types of proteins that control transcription or different types of proteins that control DNA replication and cell growth so a lot of different effects that can come just from this one single pathway alright now that we know that this next pathway is going to be even easier okay so let's go ahead and zoom in on this pathway now but now I'm actually going to draw them over here I'm actually going to redraw them over here so we don't run out of room so let's actually draw him right here now the difference between this protein and the one that we just did is depending upon the g-protein so it just really depends upon the actual g-protein so we mentioned gee stimulatory protein I'm going to mention another different type of protein this protein is actually going to be called GQ okay this is called GQ protein now there's certain types of hormones that can activate this pathway and I'll explain which hormones for right now just let's go with um oxytocin so let's say for this one we say oxytocin okay so oxytocin comes in and binds on to this receptor when he binds on to this receptor activates this GQ protein what was the GQ protein bound to originally it was originally bound to g.d.p but when this oxytocin finds on to the receptor it changes its shape and activates the GQ protein so what does it do it actually binds on gtp and gets rid of the GDP all right now it's active right so it's active what does this GQ protein going to do we know there's enzymes again on this actual cell membrane what does this enzyme that we could have here let's draw this enzyme right here look this guy so this guy is kind of like a blockhead right look at this alright and what's he going to do he's actually going to have a specific domain over here that when this GQ protein binds on so let's show the GQ protein coming over and binding on perfectly to this point right here so there the GQ protein binds and the GQ protein is bound to G T P right same thing is going to happen but this enzyme right here is very very specific this enzyme is called phospholipase C what does phospholipase C do well he does the same thing that they identify cyclase does so he has a little ear over here look at an ear his ear that's a heck of an ear right it has this little cutting domain and what it does it actually cuts the gtp what is it cut it cuts the third phosphate on converts gtp into GDP what is GDP due to the g-protein it turns it off while gtp turns it on so now this g-proteins off then what happens is phospholipase c will cut a specific molecule in the membrane this specific molecule that it cuts in the membrane is actually called pip2 which stands for phospho and a sytle diphosphate what does this guy do now look at the other part of them so now he's got this actual look at his chin his chin he's got this little part right here that it loves to cut like it's going to cut this actual pip2 so what does this guy do he has this part here that cuts the pip2 and it breaks it into two different fragments what are those two fragments alright one fragment that it breaks into is called specifically it's going to break down a to D AG which stands for die a seal glycerol and the other component of it is actually going to be ip3 which stands for an acetyl triphosphate now da G which is the diacylglycerol he can go and activate a specific enzyme that specific enzyme that he can activate it's actually called protein kinase C okay so he can go and he can activate a specific enzyme let's say that specific enzyme is called protein kinase C so now look it activates this protein kinase C and what can this protein kinase you do just what the protein kinase a could do so well let's just actually write that out what could you do you could do phosphorylation of various proteins and then what's the overall result it all depends phosphorylation of proteins we said can either change the membrane permeability it could change the at it could actually control metabolic pathways it can control the protein synthesis it can control cell proliferation you know sometimes phosphorylating a protein can even inactivate the protein too so phosphorylation doesn't always activate something it can also deactivate something okay so that's the point there what is ip3 do okay you know most cells have what's called a smooth endoplasmic reticulum so let's say I draw here a smooth endoplasmic reticulum so here's our smooth endoplasmic reticulum on the smooth endoplasmic reticulum or even in certain cells like muscle cells they have what's called a sarcoplasmic reticulum so this could be a smooth ER so I'm going to put here it could be smooth ER or it could be a Sarco plasmic reticulum it just depends on the cell so it could be one or the other so if it's in like a general cell that's not a muscle cell be a smooth ER if it's in some type of muscle cell could be a smooth sarcoplasmic reticulum right like cardiac muscle or like the actual skeletal muscle and a little bit in smooth muscle but anyway what's the point here on this smooth ER or this sarcoplasmic reticulum they have the specific scepters for ip3 let's draw the specific receptors here's the specific specific protein and on this protein has a very specific receptor let's say let's say that in blue here's this receptor and that's for IP 3 IP 3 comes in and binds on to this receptor when he binds on to this receptor it opens up a specific channel and guess who starts flooding out into this area calcium so calcium is going to start getting pushed out into the cytoplasm what's the significance of calcium calcium loves to bind on to calmodulin and guess what kind module and helps to do it helped helps activate surface if acidic types of kinase is and those kinase ins can perform various different types of functions okay some of them could be kinase could phosphorylate different types of proteins to initiate contraction if it's a muscle cell and that's why I want to mention so let me actually mention this right here so again calcium can actually come in let's actually show it over here can bind on to what's called calmodulin and when it binds on to calmodulin it can activate other different types of kinase a--'s so when this actually can come and activate other different types of kinase is and then again what can kinase is do you can just draw this going in right here look it can phosphorylate various different types of proteins right and what can I do in this case here's what I wanted to mention why I mentioned oxytocin so oxytocin is a very very specific one because we know oxytocin is important for being able to regulate contractions right of the actual uterus or of the myoepithelial cells in the milk ejection or the vas deferens all that stuff how remember I told you it was designed to increase calcium inside of the cells this is the mechanism that it works through so oxytocin can actually activate this pathway to increase the calcium levels in the cell why because calcium can either by onto troponin or it could activate calmodulin and those could activate kinase Asst they can phosphorylate different types of proteins like myosin and then to what trigger muscular contraction but that's obviously not the only thing that could happen with this pathway it could also phosphorylate various different pride types of proteins that can control membrane permeability cell proliferation all right so it can still do all of these different things that we showed up there it can control metabolism it can control cell proliferation protein synthesis various different types of pathways okay that covers that one now we're going to finish up with one more okay one more pathway here let's actually show him over here on this side all right so let's show this guy in red so I can show them inside of the nucleus okay so this is actually going to be for the steroid hormones now okay now there's a receptor right there it's an intra nuclear receptor now I told you steroid hormones have receptors either inside of the cell right and inside of the cell means it could be intra site of Sallah or it could be inter nuclear it honestly depends upon the steroid hormone okay so usually these guys when they're not bound to steroid hormones they're bound to something which is referred to as HSP which stands for heat shock proteins now a steroid hormone what do we say it can diffuse right through the lipid bilayer so let's show that and blue here so here is my steroid hormone and I take for example this steroid hormone this could be testosterone okay but it could have been any of them I'm just picking this one as an example and what does it do it actually moves right through the membrane so we can show it actually diffusing through the membrane then what does it do it actually can actually move either if it's in the cytosol it can bind onto that receptor displacing the heat shock proteins or if it's in the nucleus it actually will move right into the nucleus and look when it binds on to this actual intra cellular receptor it displaces the heat shock proteins now the heat shock proteins are displaced this receptor that it binds onto is not very active and look what it can do it can bind onto a specific gene sequence what is that gene sequence that it binds on to let's say I highlight this portion that it's by binding onto I'm highlighting this this right here this specific gene sequence is called a H R you know what that stands for that stands for hormone response element so it's a specific gene sequence that whenever these actual hormone receptor complexes bind on to that gene what could it do it could trigger a plethora of effects it could cause the cell to start proliferating so it can stimulate mitosis it could stimulate the synthesis of more proteins and what could those proteins do they could do very simple things they could control metabolism they can control ion permeability they can control protein synthesis there might be structural proteins there could be functional proteins if you control cell growth we don't know right it just depends upon the hormone okay so again understanding this is critical that testosterone can actually do what move right through the cell membrane it can bind onto an intracellular receptor whether it's in the cytosol or in the nucleus that receptors normally bound to heat shock proteins but when testosterone binds it displaces the heat shock proteins and when it does it can actually activate called a zinc finger but we're not going to talk about that and that can bind on to this specific gene right which is called a hormone response element what would that do that can actually undergo what it can undergo mitosis oh you could actually cause DNA replication or it could stimulate translate i'm transcription and then translation to make different types of proteins okay last thing i want to mention here is we mentioned how we stimulate all these pathways well how do we inhibit it because we can't have these things you know we had this GQ protein coming over here and binding onto this guy and then this whole pathway was occurring how do we actually inhibit this process from continuing to occur because this cyclic AM P is rising in the cell right so this cyclic GMP is rising in the cell how do we prevent that cyclic GMP from continuously rising and rising and rising okay you can use and you can also do this for this phospholipase see you can use an enzyme and this enzyme is called so look at this I'm going to show this enzyme like this here's this enzyme and this enzyme loves to be able to eat the cyclic AMP II whenever it's time what does this enzyme called this enzyme is called p d e pv e stands for phosphodiesterase so phosphodiesterase loves to be able to break down and degrade the cyclic AMP II why because the cyclic a and P levels increase so much it's just going to continue to keep stimulating the cell so to inhibit it we have to have these phosphodiester raises which will start breaking down this cyclic AMP e alright and this can also do that to these phospholipase phospholipase enzyme also so you can also have that enzyme over there that phosphodiesterase molecule select here he is this is also called phospho diester s and this could also occur in multiple different types of pathways but just understanding that these enzymes are the ones that are breaking up the cyclic AMP E or they could be breaking up to phospholipase C or other different types of enzymes to prevent these pathways from continuously occurring alright alright guys I hope this made sense in this video we covered the G stimulatory proteins we covered the G Q proteins we covered the testosterone pathway we discovered why certain types of peptide hormones have to work on extra cellular membrane receptors and we discuss why steroid hormones can actually have intracellular receptors obviously we didn't cover all the different types of receptor pathways in this video I hope it made sense thank you guys ninja nerds until next time

Channel: Ninja Nerd

Views: 568,470

Keywords: receptor pathways, endocrinology

Id: RMV130vU8gA

Length: 28min 3sec (1683 seconds)

Published: Thu May 11 2017