Membrane Bound Receptors and Secondary Messengers - Video Tutorials & Practice Problems
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1
concept
G Protein-Coupled Receptors
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9m
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Hormones induce changes in target cells because those target cells have a very specific receptor for that specific hormone. But we've said these receptors can work differently because we have different types of hormones. Steroid hormones can pass through the cell membrane. Most amino acid based hormones cannot pass through the cell membrane. So now we wanna think specifically for these amino acids hormones. How can it induce a change inside the cell if the hormone itself has to stay on the outside of the cell? So to do that, we're gonna talk about second messenger systems and specifically, we're gonna talk about G protein coupled receptors, all right, G protein coupled receptors or we can also just write G PC RSG PC RS. This is a class of membrane bound receptors that initiate signaling cascades. And I wanna come back to this word cascades in just a second. But first, I just wanna say it's a class of membrane bound receptors. This is a huge group of proteins and actually, most of them are not involved in hormone signaling. G protein coupled receptors are the options in your eyes. They're what recognize scents in your nose. They bind to neurotransmitters in the nervous system. They're used all over the body. In fact, roughly 5% of you the genes in your genome code for G protein coupled receptors. Now, we're talking about the details here because for understanding how hormones induce changes in cells, it's really important to understand how these G PC Rs work. All right. So now this word cascade, we say that they are gonna initiate these signaling cascades. Well, a signaling cascade. Well, a cascade, you can think it's like a waterfall, right? So as it goes, it picks up speed, it picks up more stuff with it and it sort of gains momentum, it, it gains speed as it goes. So we're gonna say a signaling cascade is when chemical messengers are linked in series, there's all sorts of different types of signaling cascades. But here we're gonna talk about the cyclic A MP or cyclic adenosine monophosphate signaling cascade. And we can write that just as C A MP, that's typically how we'll write it. The cyclic A MP uh signaling cascade is one of the most common examples of a signaling cascade. And if you have to learn the details of one signaling cascade, it's almost certainly going to be the details of this cyclic A MP cascade. So that let's look at the details. All right. So we have this illustration down here and just to orient you, we have the cell membrane and above the cell membrane up here. That's gonna be outside the cell and below the cell membrane will be inside the cell. But we're talking about hormone signaling. So we have all these molecules that are drawn around here. We'll go through them all one by one. But the first one we want to look at is this molecule right here. That's the hormone and that's epinephrine drawn out just to be clear. It's drawn a lot bigger than it would be. It's not really to scale. But for illustrations, this works. So we have this hormone, it's outside the cell, it can't cross the cell membrane. So it's gonna bind to this receptor that we see here in blue and this receptor is going to be a G PC R. So this G PC R, this blue receptor here, you can see it's bound to the hormone, but it's a big protein, it goes all the way through the membrane. And so it's able to transmit the signal across the membrane, right. So that brings us down to number two here. It says that our receptor or our G PC R, it's going to activate a G protein and the G protein you can see here, we have illustrated as this green protein right there. Uh sort of attached that G PC R there. Well, G protein, that's where that gets its name the G protein coupled receptor. Because the way this is gonna work is when it's activated, it's going to replace on that G protein. GTP is gonna replace GDP on the G protein. All right. GTP. GDP. Let's straighten that out. GTP. Well, that's very similar to the molecule. A TP, adenosine triphosphate is a TP. Guana zine triphosphate is GTP. So this is a high energy molecule. And GDP. Well, that's very similar to ad P again, adenosine diphosphate. This is guana zine diphosphate. So, here we're just replacing this sort of lower energy GDP with a higher energy GTP. And that's gonna activate this G protein. And now we can go over to three, once activated, it gets released from this G PC R and the G protein diffuses along the membrane. So you can see here we have it diffusing along the membrane. These G proteins are proteins, but they have a hydrophobic portion that's inserted in the membrane. So they're stuck on the inside of the cell there, they're stuck right up against the membrane. So it diffuses across the membrane until it binds to and activates the enzyme. And we have this enzyme drawn here in pink, it bound to and that enzyme is gonna be a dilate cyclist. All right, a dentate cycle. So that brings us up to number four, when a dilate, cyc lase is activated. A dilate cycle's job is to convert a TP that high energy molecule in the cell. Two cyclic A MP or as I'm writing here C A MP. And we can see that illustrated down here here, we have an A TP molecule with the adenosine and 123 phosphates. And it interacts with adenylate cycles. And then on the other side, here, we have this cyclic, a MP, a cyclic adenosine monophosphate. So we can still see the adenosine but it now has one phosphate on it. It's called cyclic because this phosphate is actually bound to the adenosine in two places making a little ring. Now, that's probably more biochemistry than you really need to know. But if you're wondering where the name comes from, that's where it comes from. Now, real quick helping you remember a dentate cyc lase. Well, a dentate. Well, you can remember it inter it interacts with cyclic adenosine monophosphate and then cyc lase. Well, it makes cyclic A MP. So what that enzyme does is right there in the name and it lines up with the word that you need to know for what it produces. All right. So now this adite cycle is making a whole bunch of cyclic A MP. That means we can go over to five cyclic A MP. Now this is just in the cytoplasm and it is going to bind to the enzyme, protein K A protein kinase A and protein kinase A. Well, it's a kinase and kinase jobs are to phosphorylation other proteins. So now this is an enzyme that again, it's in the cytoplasm and it's going to go around our kinase here, we're gonna go down to number six, this kinase is gonna phosphorylation proteins and as it phosphors proteins, it's turning proteins on or turning them off and that is going to cause or trigger our cellular response. Now, it's gonna turn on all sorts of different proteins depending on what the target cell is. And those proteins then go on and can do all sorts of things. Again, depending on what the hormone is, depending on what the target cell is and that is what gives you our cellular response. So again, we started with this hormone outside the cell and now we have a response coming from this kinase on the inside of the cell. All right, I said, if you need to know the details of one signaling cascade, it's likely gonna be this one. And I realized that I've sort of thrown a bunch of vocab at you here and put it in a very specific order that might be a little tough to remember. So we've put together a little memory tool for you here. And so to help remember this, we have this camper and this guy is sitting at a campfire roasting a marshmallow and it says that he is at camp Kines. All right. And our memory tool is holding really great activities at camp Kines. All right, let's go through this. So remember, the first step is the hormone comes in and that hormone, well, we have h for holding the hormone binds to a receptor, the receptor, we have R and the word really, the receptor activates our G protein. The G protein. Well, that's the G in great. The G protein activates a dentate cycle. Well, a dentate cyc lase that matches up with the A in activities. A dentate cyc lase produces cyclic A MP or as we write it C A MP. Well, that's just the word camp cyclic A MP activates a kinase. And while we're at camp kinase, so again, holding really great activities at camp kinase that matches up with the hormone activating the receptor, which activates the G protein, which activates a dentate cycle, which produces cyclic A MP which activates AR kinase. All right, we're gonna talk about this in more detail going forward because again, we said that this is a cascade and I said as part of a cascade is that it can get bigger as it goes. So, one thing we want to talk about is how do we start with just a few hormones and end up with a massive cellular response. So we're gonna talk about that. And we also just wanna know, I said, if you need to know one, it's likely this one, but there are others. So we just wanna see how different signaling cascades can produce different responses. And so we'll compare some in that way. I'm looking forward to it. I'll see you there.
2
example
Membrane Bound Receptors and Secondary Messengers Example 1
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2m
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Our example, gives us the steps of a signaling cascade and it wants us to put them in order by writing the correct letter on the blanks here. So before we do this, remember, we had a memory tool for remembering the cyclic A MP signaling cascade. So I'm gonna write that out first. And my memory tool was holding really great activities at camp kindness, holding really great activities at KK. And the first letter of each one of those words matches up with one of the major players, one of the molecules in each one of these steps. So as we go through, we see the order here is gonna start with a hormone binds an extracellular receptor. Well, that's our first two letters here with the hormone binds a receptor binds to a receptor. I'm gonna cross those out because we already have those down. And then we're gonna say, well, from the receptor, we go to something with G, the receptor activates a G protein. So I think that's gonna be my next step. And there it is C, the G protein is activated. So I'm gonna put C on the line here and uh just cross this out to keep things organized. All right. So then we go from our G protein to something that starts with an A. So remember the G protein activates a dentate cycle. All right. And a dental eight cyc lase is activated. That's right there. That's option D. So I'm gonna put D on the next line and I'm gonna cross this up again just to keep things organized. All right. So now our dentate cycle, this enzyme is activated and adite cyc lase is gonna go to camp. Well, H stands for cyclic A MP. So, a dentate cyc lase is gonna produce cyclic A MP. And that's option B here A TP is converted to cyclic A MP. So I'm gonna write B on my next line, cross this out down here just to stay organized. And then finally, cyclic A MP is now in the cytoplasm and it's gonna go bind to a kinase. All right. Well, look at that. Our option here. A protein kinase is activated. It's activated when cyclic A P binds to it. So that's gonna be A is next. And kinase is gonna go out kinase phosphors protein. So it's gonna phosphor all sorts of proteins and that's gonna lead to our, so their response and we did it, we got from a hormone that can't cross the cell membrane. It stuck on the outside of the cell. We went through this signaling cascade using secondary messengers to initiate a cellular response. That's how we do it.
3
Problem
Problem
What is the role of G proteins in GPCR signaling?
A
Catalyzing DNA synthesis.
B
Initiating apoptosis.
C
Transcription of mRNA.
D
Activating downstream effectors.
4
concept
Amplification
Video duration:
5m
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An amino acid based hormone typically induces a response in a cell by binding nuclear receptor on the outside of the cell. Often at G PC RG protein Coupled Receptor and initiating a signaling cascade inside the cell. And we said that word cascade is meant to evoke something like a waterfall where it's picking up speed, picking up momentum, getting bigger as it goes. That idea of getting bigger as it goes, we're gonna call amplification. And we're gonna look at that in more detail here. So first, let's just remember that a signaling cascade is this series of linked chemical messengers where they passed the signal off from one to another. And we looked at an example of that when we looked at the cyclic A MP signaling cascade. Well, this idea of amplification is gonna be when one molecule in that pathway passes the signal to multiple molecules and that's gonna increase. And we'll signify that with an up arrow the total amount of signal. Now, when we looked at how that cyclic A MP pathway works, we just said, you know, this molecule activates the next molecule, but there's gonna be times when it activates. Actually multiple molecules. And we're gonna illustrate that using these sort of personified happy little molecules here. And these are the molecules of the cyclic A MP signaling pathway. And here they're all holding a cell phone and they're sending a message from one to the other a text message or AD M or something like that. And we're gonna say there's gonna be a couple key places in this pathway where the, the signal is amplified. We're gonna say that the cyclic A MP secondary messenger systems are amplified when and then we have three specific places here. So let's take a look. But we're gonna start with our happy little hormone here. The hormone starts the signal by sending a message to the G PC R, this blue G PC R here. But it sends that signal by actually physically binding to the G PC R. And A hormone can only bind to one G PC R at a time. So we're not gonna get any amplification here, but that G PC R is gonna activate multiple G proteins. And so our next little figure in the line here, this green G protein, well, this G pr is gonna get the signal but it's actually gonna pass it off to multiple G proteins. Now, these G proteins have the message and they're gonna go out and diffuse across the membrane and they're gonna pass the message off to their friend here. A dentate cyc lase that we see in pink label that as ac but again, g proteins have to actually bind to ad dilate cyc lase and ident cycle is only active when the G protein is bound to it. So again, we're not gonna get any amplification. Each G protein just sort of sends this message off to one identa cycle, but a dilate cycle is an enzyme. And so it's catalyzing chemical reactions and enzymes tend to catalyze chemical reactions really, really fast. So, dilate cyc lase produces many, many cyclic A MP molecules. So here ident cy lace is gonna send this message on to the cyclic A MP that we see here. But again, it's gonna amplify because it's sending it to each individual's identity cyclist is sending that message to many, it's making many cyclic A MP S. Well, cyclic A MP S are gonna send the message off to its little blue friend here. A K. But again, cyclic A MP act actually has to bind to the kinase for the kinase to be active. And you actually need a few cyclic A MP S bound to the kinase for it to work. So you're not gonna get any uh amplification here. Again, it's gonna stay relatively the same. But again, ar kinase, ar kinase is an enzyme. So protein kinase is gonna phosphor many, many proteins. So you can see already from one hormone, we have many kinas and those kinas are now gonna go out and phosphorite whole bunches of proteins and then those proteins, some of those are gonna go off and activate even more molecules. So we can start with very few hormones. Here we have one but like accountable number of hormones binding to receptors on a cell. And that can in turn induce this change that results in literally millions or billions of molecules being activated inside the cell. And that can induce a huge physiological response. So again, this process of amplification because at certain steps in this process, the message gets amplified, it gets sent on to multiple molecules. You can have a very low hormone signal, induce a very large physiological change. All right, we're gonna practice that more in examples and practice problems of all. You should give them a try.
5
example
Membrane Bound Receptors and Secondary Messengers Example 2
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4m
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In this example, it says the image below shows a signaling cascade using cyclic A MP as a second messenger. We wanna circle the places on the image where amplification can happen. And we see this image here that we've seen before showing our cyclic A MP signaling cascade. Now, one tricky thing here is that this image isn't labeled. So the first thing I wanna do is write down the molecules involved so I can label them or at least label them as we go. Remember, we have that memory tool for that. I said holding really great activities at camp K. All right. So our first thing that happens, we have the H and the R the hormone binds to the receptor. So here we have the hormone and it's binding to this blue receptor here which I'm gonna label as a G PC rag protein coupled receptor. All right. Can we have amplification here? Well, one hormone can only bind to one receptor at a time. So we're not gonna get any amplification at this step. So next, what happens? Well, now the G PC R is activated, it's bound to the hormone. So it's gonna pass the signal on to this G here. And this G is going to be our G protein that we see in green and it's gonna activate the G protein and we have amplification here. Absolutely right. This G PC R can actually uh modify multiple G proteins and, and activate them. So, as long as that hormone is bound to the receptor, it can continue activating G proteins. Now, this G protein is gonna go along to our next thing. A so it's gonna diffuse across the membrane here. Remember, and it's gonna bound, bind to this enzyme A and A stood for a dentate cycle which I'll label as ac here. And so do we have amplification at this step? Well, with the G protein binding to a dentate cyc lase, well, one G protein can only bind to one a dentate cyc lase at a time. So we don't get amplification and that Aden cycle is only active when it's bound to the G protein. So no amplification there. Our next step, we're looking at this cyclic A MP. So here we have the A TP being converted into cyclic A MP. Can we get amplification there? Absolutely. This ad dilate cyc lase, this is an enzyme. So it's gonna catalyze this reaction that converts uh A TP into cyclic A MP and it can catalyze it very quickly. So it's making a whole bunch of these cyclic A MP molecules. Well, the cyclic A MP molecules then go out and bind to a kinase. So here's our kinase. Are you gonna have amplification at that step? Well, not at the step of the cyclic A MP binding to the kinase because again, the kinase is only active if it's bound to cyclic A MP. So the cyclic A MP can only bind to one kinase. But remember here, we'll label our kin, what does the kinase do? A kinase phosphors other proteins and it can do that pretty quickly. So I'm actually gonna draw some arrows coming out of a kinase because this is phosphorylation, other proteins resulting in our cellular response. And that is another place that we can definitely see amplification. All right. So again, amplification, we can start with one or just a few hormones signaling to the cell. And because at these steps, we can get multiple molecules passing, getting the signal passed to them, we can amplify the signal and we can end up with a very large cellular response from the kinas in the end. All right. Four problems at all. I'm gonna try.
6
Problem
Problem
Hormones can bring about substantial physiological changes at very low concentrations. How does this relate to the concept of second messenger systems?
A
Second messenger systems act more quickly, creating a larger cellular response.
B
Second messenger systems modify the DNA directly, allowing the hormone to make an impact even at low concentrations.
C
Second messenger systems prevent hormones from being degraded so they can exert their effect for a longer duration.
D
Second messenger systems amplify the original hormone signal, allowing it to work at low concentrations.
7
concept
Secondary Messengers
Video duration:
10m
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Whether or not a hormone induces a change in a cell depends on whether that cell is a target cell. And whether or not it's a target cell depends if it has the correct receptor for that hormone. But different target cells will respond differently to the same hormone. And so here we want to really break down how and why that works. We're gonna do that by talking about signaling using different secondary messengers. Now, we've already introduced the second messenger cyclic A MP. We're gonna review that here, but we're also add a little twist to it. And then we're also gonna talk about the second messengers dag and IP three. So we'll start out by saying that hormones may induce different signaling cascades depending on a few things. Here. First, the presence of a specific receptor. Now, here we're still talking about these G PC Rs, these G protein coupled receptors, but one hormone might actually bind to several different G protein coupled receptors. And these different G PC RS are gonna be used by different cells and the different G PC RS will cause a different signaling cascade inside the cell. Now, one of the main things that can be different for these signaling cascades is the second messenger used. So, depending on what the second messenger is in the cell that's gonna turn on or turn off different things in the cell and you'll get a different response. Now, even further down the line, we have the activity of the Kines often. What happens in these signaling cascades is that a kinase gets activated and kinas go out and phosphor different proteins. But we may activate or uh different kinas and even the same kinase may have different effect in different cells. And that's just because different cells have different proteins. So for example, the same kinase in a cardiac cell versus a liver cell is gonna have a different cell. The response because those cells just have different proteins inside of them. All right now to break this all down, let's let's go through these different signaling cascades. We'll start with the one we know the cyclic A MP signaling. So this starts with a hormone that hormone binds to a G PC R, that G protein coupled receptor. The G PC R activates a G protein. The G protein diffuses across the membrane binds to a dentate cyc lase Aden cycle is then activated when it's activated, it converts that A TP into cyclic A MP, cyclic A MP then binds to protein kinase A and we have several arrows coming off the bottom of that protein kinase A because it's gonna go out and it's gonna phosphor a whole bunch of different proteins in the cell and that's gonna cause that cellular response. Well, here we've talked about making cyclic A MP. But another response the cell may do is to inhibit, or we're gonna say here's cyclic A MP signaling inhibition. So, to break this down, we'll start going through the same way we did. We're gonna have a hormone, it might be the same hormone is gonna go out and in a different cell. Well, it's gonna bind to a G PC R but it's going to be a different G PC R structurally very similar. But how it responds is gonna be slightly different. It's gonna respond by activating a G protein, but it's a different G protein again, structurally similar, but it's gonna work slightly differently. This G protein is gonna go, it's gonna diffuse across the membrane and it's gonna bind to a dentate cycle. But instead of activating a dentate cyc lase, I'm gonna draw a little down arrow here because it's gonna block the function of a dentate cyc lase. Well, if a down cycle is turned off, well, that means the A TP in the cell just stays A TP, it doesn't get converted to cyclic A MP. And so we have the cyclic A MP grade out. We're not making cyclic A MP. If we're not making cyclic A MP, the cyclic A MP can't bind to the protein kinase A. And so I'm gonna draw a little down arrow here to say that we're sort of shutting off that protein kinase A and we don't have any arrows coming off and at the bottom it's not going out in phosphor proteins. We're causing a very different cellular response in many ways, almost the opposite cellular response because instead of making cyclic A MP, we're blocking the production of cyclic A MP. All right. Well, we may also use just completely different secondary messengers. So here we're gonna look at this dag and IP three signaling using these two molecules as second messengers. So again, we'll have a hormone go out. It might be the exact same hormone. It's go going to bind to a G PC rag protein coupled receptor. It's a different G PC R again, structurally, very similar, but a different one, it's gonna activate a G protein again, structurally similar. But a different G protein, the G protein is gonna go out, it diffuses across the membrane and it binds to an enzyme, but it's a different enzyme. This time, it binds to phospho lipase. See, and phospholipase C does something completely different from adite cycle. What it does is it takes this molecule P IP two or sometimes you just call it pip two. Now, this stands for a much longer chemical name that almost certainly you don't need to know. We'll just call it pip two. It takes pip two and it breaks it into two smaller molecules. Dag and IP three. Again, these have longer chemical names that almost certainly you don't need to know. So now we have these second messengers. Dag and IP three. Well, dag goes out and it binds to a protein kinase, but it binds the protein kinase. C a completely different protein kinase that is now activated and it's gonna go out phosphorylation proteins in the cell, but it's gonna be a completely different set of proteins. It's phosphorylation. IP three is gonna do something different. IP three is going to cause the release of calcium ions from stores in the cell from places like in the endoplasmic reticulum. Most calcium ions will have numerous physiological responses. A major one is that they're gonna turn on sort of through a couple steps, they're gonna turn on other protein kinas, those other protein kinas are gonna phosphorite all different sets of proteins. All right. So here you see, you can start with the same hormone and by just changing the G PC R that it binds to, you can get very different responses in the cell. Now, to look at this, I just wanna look at one example and you almost certainly aren't responsible for the specifics of this example, but I think it's illustrative. So we're gonna look at epinephrine. Now, epinephrine is the same thing as adrenaline and we've been using this hormone sort of example as we go. Well, epinephrine is uh active in the fight or flight response. So, one thing that happens is that during their fight or flight response, you release epinephrine and it's gonna bind to these G PC RS called beta two receptors. And these beta two receptors are expressed in Bron and bronchiole smooth muscle. And your bronchioles are the airways that go down into your lungs. Well, in these bronchial smooth muscles, the beta two receptors set off this cyclic A MP signaling cascade. And so I'm gonna draw an up bureau here. We're gonna get more and more cyclic A MP in the cell that's gonna turn on protein kinase and that's gonna result in vasodilation, vasodilation. Those airways are gonna relax, they're gonna get bigger. And that makes sense for a fight or flight response, right? If you need to run somewhere or fight something, you want your airways nice and open. So you get all the oxygen you need. It's also why epinephrine is used in an EpiPen because if you're having an allergic response and those airways are closing down, the epinephrine will cause this response and cause them to open up again. All right. But regardless, we have epinephrine causing one response in these bronchioles. But the same hormone will go out and will bind to a different G PC R. These alpha two receptors that are in arterial smooth muscle. Now, this is in specific arterials that are going towards places like your skin. And in this arterial smooth muscle, these alpha two receptors cause a cyclic A MP response. But this is that cyclic A MP inhibition. So I'm gonna draw a down arrow there. So now we're blocking the production of cyclic A MP. Well, if you block the production of cyclic A MP, you get less protein kinase. A turn on. If you get less protein kinase, a turn on in these cells, you get vasoconstriction or at least it blocks the vasodilation. And now that makes sense for blood vessels going to places like your skin. If you need to run somewhere or fight something, you don't need to worry about blood in your skin, you want it in your skeletal muscle. So you're gonna squeeze down on those places where you don't really need the blood to go. All right, but we're not done, this same hormone is going to also bind to another type of G PC R called an alpha one receptor. These alpha one receptors are in the same arterial smooth muscle cells. These alpha one receptors cause a completely different response. They cause this IP three NDAG signaling response. And so here I'm gonna draw an up arrow because we're getting more and more IP three and dag in the cell. Well, this results in a whole different cellular response. A whole different set of proteins being phosphorated here, but it's also going to cause vasoconstriction. So before we sort of didn't block vasodilation with that, those alpha two receptors, now we're actively constricting. And so here, we're reinforcing, using a whole different signaling cascade, reinforcing that cellular response and making sure that these blood vessels really close down. So again, we have one hormone causing three different signaling cascades, two of them happening in the same cell. And so when you think of these, what are relatively simple things, a hormone, a single molecule going in the blood, how does it cause different responses in all these different cellular tissues? This is how, all right, like always we have an example and practice problems to follow. You should give them a try and I will see you there.
8
example
Membrane Bound Receptors and Secondary Messengers Example 3
Video duration:
8m
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My example tells me that the image below shows a part of a signaling cascade that uses IP three and dag as secondary messengers, we need to label each component and circle the places on the image that are different from a signaling cascade that uses cyclic A MP as a secondary messenger. All right. So as I look down here, we have a list labeled A through H these are the things that I need to label on my image here. And in the image where we have this image of a membrane and all these molecules around it with a whole bunch of blanks that I'm gonna need to fill in. And I see the membrane and just click for reference that uh outside the cell is gonna be on this side of the membrane and inside of the cell is gonna be on the bottom down here on this side of the membrane. And when I look at it, it looks very similar to what we labeled for that cyclic A MP signaling cascade. But I already see some key differences here. Now, as I go through this, we've learned the cyclic A MP signaling cascade pretty well, and the way I wanna do it is I wanna know that one really well. And then remember the differences for other stuff. And I also want to do that because I have a memory tool telling me the parts of that signaling cascade. So if I can start there, I can start labeling things and then I'll be able to see the parts that are different right away. And that's part of what we have to do here anyways. So remember our memory tool for that was holding really great activities at Camp Ks. So holding really great activities at Camp K. All right. So now let's see what matches up here on this list. Well, that h that H was for the hormone and we're always gonna start with a hormone. And so in our image here, we see that hormone right there and hormone is letter E. So I'm gonna cross that out and I'm gonna write e next to the hormone, the hormone is going to bind to the receptor. And that's what the receptor, that's what the R in that uh memory tool stands for the receptor. In this case, a G protein coupled receptor as we look down F is receptor. So that's receptor. And here's our receptor right here. So I'm gonna label this one f now the receptor, this G protein coupled receptor activates a gag protein. And I see on my image here's this molecule in green that we have as a G protein being activated by that G protein coupled receptor. So I look here, oh That's B so I'm gonna cross this out and put B on the line next to my G protein. Now, remember that G protein is gonna diffuse across the membrane and it's gonna bind to this pink molecule here. This is an enzyme in our cyclic A MP signaling cascade. That was our a, a dilate cyc lase. But there's no ident cyc lase on this list because remember we said one of the key differences here, this is where it starts to really change is that this is gonna use a different enzyme. It's gonna use the enzyme phospho lipase C. So this pink molecule here, I'm pretty sure is fossil lipase C. So I'm gonna cross that out and I'll put an A on the line there and that enzyme is then going to catalyze a reaction and it's gonna produce the secondary messenger. Now, in our cyclic A MP cascade, it produces adel cycle produces cyclic A MP. But here we're producing the molecules IP three and dag. But that's what we produce. Remember we make those molecules from splitting another molecule, the molecule we split, it's gonna be that pip two or P IP two molecule labeled here C. So I'm gonna cross that out and that has to be right here. We see here, this molecule that's up against the enzyme and you can see two arrows coming out of it because get it's getting split into those two second messengers. Now, pip two here, it's actually AAA molecule that's embedded in the membrane. So it's sort of stuck up on the membrane and that's why you see it drawn like that there. Now it gets split into our two second messengers, our IP three and our DAG and we see two things coming out of here and on this list here, we have just one letter DAG and IP three. So these two things here, those are our second messengers. I'm gonna label them both as G we'll figure out which is which in just a second. So I can cross that out and then remember the two things that they go off and do well, that IP three or we'll start with the DAG. Remember the DAG goes off and it activates a kinase specifically, it activates protein kinase C. So when I look here, this here looks more like uh an enzyme that could, something that could be an enzyme, a kinase, that molecule there. So I'm pretty sure that that's gonna be my option. D my kinase. So I'm gonna put d on the line there, non cross kinase. And then uh our IP three, remember it goes off and it causes the release of calcium ions into the cell. And while they're not to scale this sort of looks like what I might imagine how you draw calcium ions. Uh And so here we have our calcium ions and calcium ions here are H so I'm gonna cross out that and put an H here. Now, that means while we labeled both of these G, this one must actually be the IP three and this molecule up here is actually the dag. All right. So we've labeled our diagram. Now, we wanna go through and try and figure out how is this different from our cyclic A MP cascade? Which parts are the same and which parts are different. Now to be really technical, all the parts except for the hormone are going to be different. It's gonna use a different G protein coupled receptor. It's gonna use a different uh G protein, um et cetera, et cetera, et cetera. But some of these things we just sort of labeled generally. And so we want to think about the things where we're specific enough to actually call them different things. We wanna call those out and then we wanna sort of see which things generally work the same way. So we started out with a hormone again, it might be the exact same hormone. So that's the same. And then next week bind to a G PC R. Now, both signaling cascades use a G PC R. The G PC R activates a G protein, both signaling cascades activate a G protein. The G protein diffuses a across the membrane and it binds to an enzyme. Both use an enzyme. But here we've been specific in the name and we're using a different enzyme in the cyclic A MP cascade. We use a dentate cycle. Here we are using phospho lipase C. So I'm gonna circle this enzyme here. We've called this something different. All right. Now, this enzyme is going to produce a second messenger. But again, we've been specific in the molecules here. So I think we can call these things out as different cyclic A MP. Remember converts a TP into cyclic A MP. But here we have the molecule right here. I'm in a circle the molecule pip two or P IP two being converted into DAG, which is not found in our other cascade and into IP three, which is in our, in our other cascade. Now IP three goes on to cause the release of calcium ions in the cell. And that's not something that we talked about as a direct result of that cyclic A and P signaling cascade. So I'm also gonna circle the calcium ions dag goes on to activate a protein kinase. Now, we've said this is a different protein kinase. It's protein kinase C versus protein kinase A that's used in the cy cyclic A and P cascade. However, here we have only labeled it as a kinase. We haven't gotten more specific here. So I'm not gonna circle this one in both cases, that molecule uh ends up being activated is a kinase. All right. So that's what I see when we get to this level of specificity specificity is different and real generally just to step back one more time. Remember this is how the same hormone can cause multiple different cellular responses in different cells because the secondary messengers used are gonna be different. All right, practice problems after this, I'll see you there.
9
Problem
Problem
You are studying how a hormone affects a cell and find that when oxytocin binds the receptor, the intracellular Ca2+ concentration increases. Based on this information, what could you logically conclude about this cell and hormone?
A
The cell uses adenylate cyclase as a second messenger.
B
Oxytocin directly interacts with the DNA of the cell.
C
The cell uses IP3 and DAG as secondary messengers.
D
Both A & B are correct.
10
Problem
Problem
cAMP, IP3, and DAG are all molecules that are used as secondary messengers. Which statement below correctly identifies a difference between the pathways in which they are found?
A
cAMP secondary messenger systems result in the activation of a kinase, while systems that use IP3 and DAG do not.
B
cAMP and IP3 are part of the same signaling cascade, while DAG is found in different cascades.
C
Adenylate cyclase produces cAMP while phospholipase C produces IP3 and DAG.
D
Both A & C are correct.
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