Stimulatory Adenylate Cyclase GPCR Signaling

Alright. So here we're going to revisit our map of the lesson on bio signaling pathways, which is down below right here. And of course, we know that we're exploring this map by exploring the left most branches first and so already in our lesson, we've talked a little bit about the G protein coupled receptors or the G p c. R s. And as we move forward in our course, we're going to continue to talk Maura, Maura, about thes GPC are pathways. And so now we're going to move forward in our map to talk about a very specific GPC are signaling pathway, which is the identity lit cyclist. GPC are signaling pathway and more specifically, we're going to be focusing on the stimulatory, a dental it cyclists GPC are signaling pathway. And so here in this interactive box right here you can write in the word stimulatory And so now that we know where we are within our map specifically the stimulatory a dental it cycles GPC are signaling pathway, we can get started on our lesson. So here we're going to introduce stimulatory, a dental it cyclist GPC are signaling which is also commonly referred to as the identity lit cyclist. GPC our system Now. This is a classic six step example slash prototype of a g p c R signal transaction pathway that's found in all of your textbooks. Now notice down below in our text were actually numbering each of these six steps that are found in our A dental it cyclist GPC our systems and also noticed that each of these numbers in our text that corresponds with each step also corresponds with all of the numbers that we see throughout our large image down below of our dental it cycles. GPC are signaling pathways. So again the numbers up above correspond with the numbers that we see down below in this image. Now, another important thing to note here is that this a dental it cycles GPC are signaling pathway is actually a cycle that begins and ends in the same place. And so that's something important to keep in mind as we move forward in this lesson. Now, in terms of what exactly this a dental it cycles GPC our system does. It turns out that it's actually linked to a wide variety of cell responses. However, that being said, it's usually associated with the ability to allow cells to generate a fight or flight response, which you might recall from your previous human anatomy and physiology courses, is just a response that gears your body for an emergency or a threat to your survival. For example, if you were to take a look to your left in your bedroom and see a bear or a lion right there in your bedroom, what would your body do? Would it prepare for a fight so that you would fight that lion or bear? Or would it prepare for a flight straight out of the room where you're just booking it and trying to get out of the way? I could tell you I'd be booking it right out of that room if I saw a bear lying in my bedroom. But what would you do? And so again, this a dental it cycles GPC. Our system is what allows yourselves to generate this fight or flight response to that emergency situation. And really, this fight or flight response is going to be initiated by the hormone that's known as epinephrine. And epinephrine is just the fancy name for the hormone adrenaline and Of course, you guys have heard your adrenaline is pumping. And of course, that's referring to the ability for your bodies to get ready for something that might require a lot of energy. And so now we can move on to talking about each of these six steps in this pathway. But before we get started, I want to point out that in the text for each of these six steps, there are some words that air color coded to the image down below. And so, in order to make sure that you're getting a complete understanding of this pathway, make sure that you're taking advantage of the color coding in these words. And so I'll make sure to point out the color coding in the text as well. And so here, in our very first step of this pathway, the hormone signaling ligand, epinephrine, or adrenaline is going to bind to the GPC are and in this case specifically the GPC are is a beta adrianne ergic. GPC are, and you can see that the Adrianne Ergic has the root in it for adrenaline, and so that connection is there. And so when this hormone signaling like an epinephrine binds to the GPC are beta agin RG pcr. It actually causes a confirmation. All shift in the GPC, our structure. And so what you'll notice is that end step number one. We actually have the lie Gand and epinephrine color coded with this blue background. And that's because down below in our image were actually color coding epinephrine with this blue background here and also noticed that the g p c R is color coded with this background. More specifically, the beta agin ergic GPC are And that's because down below in our image, you'll see that the beta agin ergic G PCR is colored with that same tan background color. And so, if we take a look at step number one down below in our image right here, which will notice is that the extra cellular lie Gand epinephrine is actually binding to the GPC are the beta agin ergic GPC are again causing a confirmation Will shift in this beta agin ergic GPC are okay and so really here in step number one. What we can say is that there is ligand binding to the GPC are again causing a confirmation. I'll shift in this GPC are And so really, that leads us to step number two of this signaling pathway. And in step number two, we pick up right where we left off, which is with the GPC. Our confirmation will shift. And so in step number two, this GPC our confirmation I'll shift that occurred in step number one is actually going to activate a stimulatory g protein G s. And by activate what we mean is that it's going to promote the Alfa sub unit off that stimulatory G protein to release G d. P the low energy form an inactive form and bind GTP, the high energy active form. And so if we take a look down below at our step number two right here, what you'll notice is that GTP is coming into play. And so originally, what you'll see is that the G protein down here is bound to the low energy G d. P. So originally, this is actually the inactive form of the G protein, and you could see the same up above and step number one. However, once this beta age energy GPC are undergoes its confirmation, I'll shift. It allows the G protein here in step number two to replace its G D. P with the high energy G, T P. And so in step number two. What we can say is that GTP replaces G D. P and that is going to activate this G protein here and that leads us to step number three, which is, of course, that with the bound GTP again, the Alfa sub unit of the stimulatory G protein G s is going to disassociate from the other sub units of the G protein the Beta gamma sub units. And when the Alfa sub unit dissociates from the beta gamma subunits, it's actually going to defuse towards a nearby affect er, enzyme. And so notice that the effect er enzyme we have color coded with this reddish background. And that's because down below you can see that the effect er enzyme is this protein that we see throughout, and so in step number three down below. What you'll notice is that once the Alfa sub unit obtains that high energy GTP, it's actually going to disassociate. And so that Alfa Sub unit, the dissociation of the Alfa sub unit, is what we see in step number three. And so if you take a look Notice that the Alfa sub unit with the bound GTP is dissociating from the Beta gamma sub units and defusing towards the effect er enzyme that we see over here and the effect er enzyme, as you can see in this image, is a dental it cyclists, which is really where this entire pathway gets its name from from the effect er enzyme. And so this leads us into step number four and in step number four. What you'll notice is that the activated GTP bound Alfa sub unit of the stimulatory G protein G s is actually not only going to defuse to the nearby effect or enzyme, but it's actually going to bind to that effect er enzyme and activate that affect er enzyme as well, since it is indeed the stimulatory g protein And so when it activates the effect er enzyme again, The effect er enzyme is a dental. It cycles which is again where this entire pathway gets its name from from the effect er enzyme. And so if we take a look at step number four way down below in our image, noticed that the, uh Alfa sub unit of the G protein not only diffuses away, it diffuses towards the identical cyclist, but ultimately it ends up binding to the identity it cyclists affect. Er, enzyme. And so what we see is that end step number four. We will see the activation of the A dental it cyclists protein, and so you can see that the activated a dental it cycles has this yellow border around it to distinguish it from the inactive version over here, which does not have the yellow border around it. And so this leads us into step number five of this pathway and in step number five, which will see is that now that the effect er enzyme is activated, the activated affect er, enzyme a dental it cyclists is going to be able to convert a TP. It's substrate into the secondary messenger. That's called C amp. Cyclic a M P. M. We'll talk more about this secondary messenger later in our course, but ultimately what happens is the production of C AMP leads to the activation of a protein known as protein kindness A or P K A for short. And so P K. A is ultimately going toe lead to the cell response and the cell response would be, for example, increasing the breakdown of glycogen and fat. And, of course, increasing the breakdown of glycogen and fat is going to give ourselves Mawr Energy and MAWR. Energy is what we're going to need if we're going to generate a fight or flight response. And so if we take a look down below at our step number five down below over here, notice that ATP is now coming into play. And so now that the Alfa sub unit of the G protein is stimulating and activating the effect er enzyme right here, three Effect er enzyme can now produce or convert its substrate a teepee and convert it into the secondary messenger See AMP. Cyclic A M P. Here. And, of course, see amp is going to lead to the activation of Peak A. And then PK will ultimately lead to the cell response that leads to our fight or flight response. And so here in step number five, what we can say is that it leads to the generation of the secondary Messenger see amp and then see amp leads to the activation of PK and PK ultimately leads to the cell response and again as we move forward in our course, we're going to talk. Ah lot Maura, about this particular process right here. But moving on to our final step. What you'll see is that it's a step. Number six is what takes us back to the original position. It allows us to go back to step number one and make this entire thing a cycle. And so, in step number six, our final step of this pathway, the G protein Alfa sub unit is actually going to slowly inactivate itself. And so the way that it does this is by Hyg allies ing. It's G T p, the high energy form into G d. P, the low energy form. And of course, if the G protein Alfa sub unit in activates itself, it's also going to inactivate the effect er enzyme as well, since the G protein is what was stimulating the effect er, enzyme, and so ultimately, when the G protein hide relies is it's GTP into G d. P. The low energy state Thea Alfa sub unit can then reassemble its original inactive form with its Beta gamma sub units and the Lie Gand can actually disassociate from the GPC are in order to reset this pathway back to the beginning and again make this and a complete cycle. And so if we take a look at our step number six down below right here, notice that the G protein Alfa sub unit right here has, uh, the ability to hide relies the GTP so you can see GTP. Hydraulics is occurring here, and so GTP gets cleaved into G d. P releasing an inorganic phosphate. And then this Alfa sub unit is able to go back and reform its original inactive form with its beta gamma sub units and the lie Gand here, epinephrine is going to disassociate from the beta Adrianne ergic. GPC are in order to reset the pathway back to what we see in step number one, and so really in step number six. What we can see is that we have the GPC our signal eyes terminated or GPC our signal termination. And again, we'll talk more about this idea here later in our course as well. But for now, what you'll see is that we've completed our entire a dental it cyclist GPC are signaling pathway and we've talked about all six of these steps. Now, I'll admit this is quite a lot of information to commit to memory. So how in the world could I expect you guys to remember all of these different steps? Well, and are very next lesson video. We're going to talk about a specific way that you guys can memorize all six of these important events that take place in this pathway, and so I'll see you guys in that video.

So when it comes to stimulatory, a dental a cyclist GPC are signaling as you guys probably noticed from our last lesson video. There's quite a lot for you guys to remember. And so how in the world are you guys supposed to remember all of the different components and events in the correct order for stimulatory? A dental a cyclist GPC are signaling? Well, that's exactly what this video is all about, helping you guys remember the most important components and events in the correct order. And so I'm really excited to share the memory tools that we've created here at clutch prep. Because I can tell you right now, I've tried searching and you won't find anything like these memory tools anywhere on any resource. So notice what we have right here in the middle is an ordered list of the most important components and the most important events that occur in stimulatory, adrenaline, cyclist GPC are signaling. And so over here on the far left we know that the extra cellular ligand, epinephrine or adrenaline is going to bind to the GPC are more specifically the beta adrianne, ergic GPC are. And that's going to cause a confirmation. I'll shift in the GPC are now that confirmation will shift in the G. P C. R. Is ultimately what allows the G protein to exchange its G. D. P. The low energy inactive form for G. T. P, the high energy active form. And so that activates the G protein? Now the activated G protein, alpha sub unit will then disassociate from the beta gamma subunits. And that alpha sub unit will diffuse towards the effect er enzyme a dental it cyclist and bind to it in order to activate it. And so the ad until it cyclist defector enzyme will convert its substrate into the secondary messenger C AMP and C AMP will then activate the protein kinase a enzyme over here or P. K. A. Which ultimately leads to the cell response. And so really this here is what you guys need to know. And so how is it that you can go about memorizing again these particular components and these events in this exact order? Well, that's exactly why we came up with this creative but fictional story to help you guys remember this particular signaling pathway. Now, bear with me here just a little bit because this story is not fully bulletproof. It's not a perfect story to help you memorize all of the different details. Instead, this story was intentionally designed to help you guys memorize the most important components in the most important events in the correct order. And so keep that in mind as we move forward. And so the plot of our story is that the cell wants to go on a camping trip. And of course within the word camping there is the secondary messenger C. AmP. And so going camping is going to represent our secondary messenger C AMP or cyclic GMP. And of course, what is the camping trip Without cooking some s'mores. And so cooking s'mores is going to represent the cell response. And so notice down below we have all of these numbers to label the steps of our story. And what's important to note is that these numbers for the steps of our story correspond with the numbers that you see up above. As well as the numbers that you see down below throughout our image. And all of these numbers correspond with the numbers from our previous lesson video for the steps of the signaling pathway. And so in the very first step of our story, of course, how could you go on a camping trip without first packing the luggage for the camping trip? And so packing the luggage is going to represent ligand binding to the G. P. C. R. And so you can think that the L. And luggage is for the L. And ligand. And so of course, we know that once the ligand binds to the G. P. C. R, it will cause a confirmation. I'll shift in the G. P. C. R. That will ultimately activate the G. Protein. And so let's take a look at our image down below. And what you'll notice is that right in the middle, what we have is our biological membrane. And so of course above the membrane here represents the outside of our cell and below the membrane represents the inside of ourselves. And so notice that on the outside of the cell, what we have is the luggage for the camping trip for the ligand. And of course we know that the ligand is going to bind to this beta ADR energy GPC are. And so when the ligand or the luggage binds to the G. P. C. R. It will cause a confirmation. I'll shift in the G. P. C. R. That will ultimately activate the G protein. And so notice that were symbolically representing are G protein as this superhero with his beta blaster and his gamma gadget. And so recall that the G protein is a hetero Try Merrick G protein, which means that it has three different sub units. It has the alpha sub unit which you can see the symbol alphas in the belly of our superhero. So the superhero here represents the alpha subunit. Then we also have the beta subunit represented by our beta blaster here and then we have the gamma gadget which represents the gamma subunit. And so notice that when we go to step number two of our story, it starts off with the alpha hero which we know represents the G protein, alpha subunit. And so this Alpha hero wants to go on this camping trip. And so the alpha hero or the G protein alpha sub unit is going to take charge of this camping trip situation. And so what he's going to do is he's going to exchange the empty gas can that he has with a full gas can so that he can go on this camping trip. And so the exchange of the empty gas can with a full gas can is going to represent GTP exchange where the low energy G. D. P. Is going to be exchanged with the high energy G. T. P. And so G. D. P. The low energy form is going to be associated with the empty gas can. And the high energy form G. T. P. Is associated with the full gas can. And so if we take a look at our image down below, notice that our hetero trimeris G protein is initially associated with an empty gas can. And so notice that we have this gas meter here and it is on empty. And of course the empty gas can is associated with the low energy G. D. P. But again, when the ligand binds to the GPC are causes a confirmation. I'll shift in the G. P. C. R. And that confirmation I'll shift in the G PcR allows the G protein to exchange the low energy G. D. P. With the high energy G. T. P. And so the high energy G. T. P. Is associated with the full gas can. And so notice that the gas meter is on full and our gas can is now filled with gas. And so in step number three of our story, the alpha Hero or the G protein alpha sub unit is going to go to rent a car in order to go on this camping trip. And so notice that a car is going to represent the effective enzyme, a dental IT cyclist. Now, when the Alpha hero goes to rent a car, he actually forgets his beta blaster and his gamma gadget behind. And so the beta blaster and the gamma gadget are not coming along. And so this reminds us that only the G protein alpha Sub unit is going to be dissociating towards the defector enzyme a dental IT cy clicks. And so if we take a look at our image down below, notice that and step number three, it's only the alpha subunit, the alpha Hero here that is going to disassociate from the beta subunit and the gamma subunit and this alpha subunit is now associated with the high energy G. T. P. Which is this full gas can. And he has gone to go rent a car and again a car represents the effect er enzyme, a dental it cyclist. And so in step number four of our story, the Alpha Hero then uses his full gas can to fill up a car's gas tank and to start the engine of a car. And so this represents the activation of the effect er enzyme, a dental it cyclist. And so if we take a look at our image down below, notice that the Alpha hero is going to use his G. T. P. Um or his full gas can in order to fill up the gas tank of a car and to start the engine of a car. And once the engine has been started of a car that represents the activation of the AD until it cyclists enzyme. And so once a car's engine has been started up, we can go to step five A. And so of course a car is going to go to the campsite. And so the campsite going to the campsite represents the production of the secondary messenger C. AmP or cyclic GMP. And so again, if we take a look at our image down below, notice that once a car's engine has been started, it can go to the campsite and again the campsite here represents the production of our secondary messenger cyclic amp, E. Or C. Amp. And then of course in step five B. of our story. Upon arrival to the campsite of course, before they can engage in any camping activities, they need to park a car and of course parking a car is going to be associated with peak a protein kinase a. And then of course once peak A uh is activated. Once they have parked the car, they can now engage in those campsite activities and they can begin cooking S'mores. And again, cooking S'mores represents the cell response