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00:00 | Sorry about that, although I'm sure just happy to start a minute late |
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00:06 | opposed to anything. All right. when we were meeting on Thursday, |
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00:13 | were we talking about? Thank active transport. Um What we're trying |
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00:24 | do with this is we were trying uh compare primary secondary active transport. |
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00:31 | had talked about passive transport. passive transport doesn't require any sort of |
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00:36 | . It's dependent solely upon gradients, . All right. So active transport |
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00:45 | the other hand, has a dependency energy being used in some way, |
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00:49 | or form two different types, active secondary, right or sorry, primary |
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00:53 | secondary, primary active transport. We uses energy directly, secondary active transport |
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00:58 | says use indirectly. Then we got by time passing and then the weekend |
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01:04 | . Was it a good weekend? . Ok. Hm. Ok. |
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01:09 | we need to work on that a bit. Ok. So our first |
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01:13 | we want to look at here is want to look at primary, |
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01:16 | So the sodium potassium A TP A is a good example of a pump |
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01:20 | . It's a good example of primary transport. We have endo activity. |
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01:26 | why it's not beeping and doing All right. So this is |
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01:29 | our pump. It has enzymatic It's an A TP A, it |
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01:33 | the A TP release energy that causes confirmational change so that you move uh |
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01:39 | out of the cell and move potassium the cell exchanges three sodiums to two |
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01:44 | . This next slide shows you like the steps along the way. You |
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01:48 | do them. At the same time you're open to the outside, you |
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01:51 | an affinity towards potassium. When you're towards the inside, you have an |
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01:55 | for sodium. When sodium binds, sits there and goes, I'm ready |
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01:59 | go out and nothing happens unless the TP is available. That's when you |
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02:04 | it inside out. And now it's I can't bind here anymore. So |
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02:07 | gets kicked out, potassium binds up then once the two potassiums binds, |
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02:12 | causes a confirmational change for the A uh ace to turn itself around |
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02:17 | back out and it releases the potassium the cell. So at the expense |
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02:21 | one A TP, we're pumping three out two potassiums in. OK. |
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02:26 | , what we're doing in the process by moving that sodium out, we're |
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02:30 | more and more sodium, we're creating and greater gradient. Does that make |
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02:34 | ? If you have a closet? you're putting ping pong balls in the |
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02:37 | , the more ping pong balls you in the more the ping pong balls |
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02:41 | to come out, right? Same of principle. So this is what's |
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02:45 | on. We're putting sodium outside, wants to come back in. We're |
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02:48 | potassium on the inside, it wants come out and it's going to try |
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02:52 | use leak channels to do so and will. But for the most |
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02:55 | you're trying to create an environment that , hey, um potential energy here |
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02:59 | want to use it and this is secondary active transport comes in. So |
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03:03 | is an example of secondary active It's a sodium. This particular example |
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03:08 | a sodium glucose cot transporter. All , sodium wants to come in desperately |
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03:15 | gradients right, potential energy glucose wants come in but you don't want to |
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03:20 | the energy to pump glucose in That would be absolutely terrible because that |
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03:26 | a poor use of energy, You worked hard for your glucose. |
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03:31 | you agree with that? Like you in line at Taco Bell had to |
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03:35 | people around you. That's a lot energy, right? So you don't |
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03:40 | to expend that energy that you're earning eating that Taco Bell. I guess |
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03:45 | energy there. So you want to energy that you've already stored up and |
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03:50 | and this is what we've done. got this large gradient for sodium. |
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03:53 | sodium binds and when sodium binds, makes the glucose binding site available when |
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03:59 | binds the co transporter changes shape so it opens up, sodium can leave |
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04:04 | glucose can leave. And this is we move glucose against its own |
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04:09 | So glucose, there's lots of glucose cells. Glucose outside cells is |
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04:14 | Would you agree with me on Yeah, because glucose is being used |
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04:18 | the cells for all sorts of So keeping glucose outside the cell is |
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04:21 | useless, but I don't want to the energy. This is how I |
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04:24 | it inside. This is just an , right? Does the example make |
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04:31 | ? So there are tons and tons tons and tons of co transporters. |
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04:36 | you think you need to memorize them ? No, if you understand cot |
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04:40 | , you think you're good. So this is just the examples you |
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04:44 | see up here there's our sodium glucose , we have amino acid transporters, |
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04:48 | have a phosphate transporter. Got all these are just different examples. Notice |
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04:54 | we see in each of these pictures , right? In each of these |
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04:58 | , we're using the potential energy for one ion say potassium or sodium. |
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05:04 | there's others for example, proton right? Or not protons pump but |
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05:10 | cot transporters that are there to move object against its gradient. This is |
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05:16 | a cot transporter does. This is active transport. All right, you |
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05:21 | see this over and over and over where you'll see a specific example, |
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05:25 | might see this actually, I know going to see this in about three |
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05:28 | . I'm never going to ask you the sodium potassium or it's NKCC transporter |
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05:34 | . But it tells you in the name sodium potassium two chlorine. And |
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05:38 | it uses the sodium gradient to pump potassium in plus two chlorine. In |
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05:44 | inside the cell no changes electrically because moving two negatives and two positives kind |
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05:49 | cool. All right, this is example of the cot transporter an exchanger |
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05:55 | the same sorts of energy, In other words, they're moving things |
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06:00 | they're moving things in opposite directions. you might see textbooks refer to it |
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06:04 | an anti port system, right? might see the co transporters referred to |
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06:08 | a SIM port system sim for same for against or opposite directions, but |
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06:14 | the same sort of thing. It's exchanger, you're exchanging one down its |
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06:18 | or down its gradient to move something its gradient. And that's what these |
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06:21 | just examples of. Again, don't , please do not memorize the |
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06:26 | right? That's not what we're We're trying to understand conceptually what's happening |
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06:32 | . This slide just shows you how these things show up and how many |
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06:36 | types of things there are. So can see kind of in this image |
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06:39 | got a pump, we got right? We have leak channels, |
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06:43 | have co transporters, we have voltage channels, we have different types of |
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06:48 | . Here's an exchanger, here's some different types of things and they're just |
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06:52 | pop up over and over and over . And so the key thing, |
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06:55 | important thing for you to take with is do I understand conceptually what an |
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07:01 | is? What a cot transporter What secondary active transport is versus primary |
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07:05 | transport versus the different forms of passive . If you understand that, I |
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07:10 | throw random names at you and you'd like, yeah, OK, I |
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07:13 | it. I understand what that right. That's the idea. So |
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07:19 | we good with this? And I have said that probably in two minutes |
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07:23 | three minutes on Thursday, but it a weekend and I figured we needed |
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07:27 | go home. All right. Any ? Yes, ma'am. Uh |
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07:40 | Yes. So, so the exchangers doing that as well, but they're |
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07:45 | the, the ion for ion. , that's kind of the way that |
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07:48 | can think about it. It's, substance for substance and usually it's ion |
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07:51 | ion, hence the term exchanger, ? But this isn't the only way |
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07:57 | get things across that membrane, Some things are too big. We |
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08:01 | about, for example, the anionic proteins, you know, and how |
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08:04 | play an important role in terms of inside of the cell being negatively |
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08:08 | I think we mentioned that if we mention that we're going to mention |
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08:12 | All right. These things are just big, but your cells are going |
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08:16 | be playing an important role of moving things that's part of its job. |
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08:21 | so it doesn't use transporters or, uh carriers to do this. |
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08:27 | it uses a mechanism of secretion using . Right now. Again, a |
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08:33 | of the stuff is going to be to you. You've probably seen this |
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08:36 | . So, what we're talking about is making a protein that it should |
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08:40 | either secreted so released from the cell into the environment, extracellular fluid, |
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08:45 | maybe you're making a protein that needs go into the surface of the cell |
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08:49 | serve as a receptor or some sort interaction with the external environment. And |
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08:55 | way you're doing this, what you're do is you're going to use the |
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08:58 | sort of production cycle to do this this is something you've already learned way |
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09:04 | when. All right, basically, you're gonna do is you take that |
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09:08 | into plasma curriculum, you make your in the rough er, right. |
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09:12 | it's a secretary molecule, it stays the uh the of the uh of |
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09:19 | uh rough er, and then what happen is portions will be pinched off |
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09:24 | then that little vesicle will move from to the Golgi, from the |
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09:28 | You'll be sorted and tagged and bagged then you'll be sent to where you |
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09:32 | to go. And that's what this trying to show you. So if |
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09:36 | being secreted, that vesicle will contain soluble proteins that will then just be |
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09:41 | outward. And if you're going to on your membrane, they're going to |
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09:44 | inserted along the way, but still through the same process. And now |
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09:48 | that vesicle comes to the surface and with the surface that uh uh transmembrane |
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09:54 | is now sticking outward, facing the environment to interact with it. |
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10:00 | when this happens, you regulate this one of two ways. All |
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10:04 | most things in the body are gonna regulated in a non constituent way, |
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10:09 | you're always just kind of producing it then when you need to actually release |
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10:14 | or put it into the surface, going to regulate the presence of that |
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10:17 | the movement of that vesicle up to surface to be released or whatnot. |
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10:22 | other way you regulate it is by uh the old production at the far |
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10:28 | end. In other words, at , at the RN A level, |
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10:31 | ? So the transcription level, all . So when you're constituently making |
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10:35 | what we're saying is we are just constantly be producing this, constantly making |
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10:40 | . And then we're not really kind controlling when we're producing or when we're |
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10:45 | or stuff like that. So this kind of like a, a cell |
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10:48 | activity, but the regulated stuff as mentioned, this can be done at |
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10:52 | level of release or it could be very much earlier. Um, but |
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10:56 | when you're, um, when you're about release, it's gonna be done |
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10:59 | right there at the release level. ? That's what we're saying. When |
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11:02 | regulated, it's like, ok, gonna have vesicles and they're just gonna |
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11:06 | sitting aside waiting for you to tell when to release that material. |
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11:12 | Anyway, here have um like like an allergic response to bees or |
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11:17 | like that, like a, like an anaphylactic response, right? No |
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11:22 | , no one has anaphylax. that's good. You do. |
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11:25 | So I'm not asking what it You could be allergic to just |
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11:29 | It doesn't matter what it is. the reason you have that kind of |
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11:32 | is because the cells are already primed ready to go. They didn't have |
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11:35 | be, oh, we just got by A B um, what do |
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11:39 | do now? It's like, we got stung, release the chemicals |
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11:43 | it's already there. That's the regulation , right? So, vesicular transport |
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11:51 | this process. All right. It's we're dealing with large things. |
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11:55 | primarily proteins, right? They're too to be using uh some sort of |
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12:01 | or some sort of um uh like , you're gonna require energy because you're |
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12:07 | with big old bubbles, right? these, these vesicles are made up |
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12:10 | plasma membrane So they are part of end the membrane system. And there |
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12:16 | a couple of different processes. when I was in your seat, |
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12:20 | had three processes. Now there's like . All right. It's just because |
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12:26 | we learn more, it's like, , well, we can divide this |
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12:28 | out. All right. So the primary processes, we go endocytosis and |
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12:35 | . And that's pretty simple. Endo in exo means out, right? |
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12:39 | basically, I can take things in I can push things out of the |
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12:43 | . Notice I have phagocytosis sitting over . Phagocytosis is a specific type of |
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12:49 | . It actually is kept separate from because this is an active form of |
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12:54 | in materials uh that you're actively hunting . All right. And it's typically |
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13:00 | by cells of the immune system like and monocytes and neutrophils. Their job |
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13:06 | phagocytosis, hunt for things that shouldn't in the body and then bring them |
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13:10 | and destroy them. But regardless if doing endocytosis or exocytosis, what you're |
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13:17 | with is you're dealing with a very flat plasma or uh plasma membrane. |
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13:22 | right. So think of the earth your flat to you to you. |
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13:29 | it feel flat? It does, it? I mean the horizon goes |
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13:33 | a pretty long distance, right? can't really see the curvature of the |
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13:38 | from your perspective, right? So our purposes, the earth is |
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13:44 | but we know better it's not If you wanted to bend the |
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13:48 | it'd be pretty hard to do from perspective. Right? And that's the |
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13:52 | thing that's true for a cell, plasma membrane, for those little tiny |
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13:57 | , the plasma membrane is pretty large pretty flatt. And this is what |
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14:01 | trying to show. You. Look how long and flat that thing |
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14:03 | All right. This is, this the and you can imagine it's going |
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14:05 | be the same thing for a plasma . All right, if I want |
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14:08 | bend that, I need help to so. And so we have proteins |
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14:12 | do that. One of these proteins heard of? All right, you've |
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14:16 | of clain, right? Do you hearing about Clari clain coated pits? |
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14:21 | right. Well, what's Clari it's class of molecule whose job is to |
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14:27 | a membrane that appears flat and bend against its will so that it bends |
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14:32 | a little tiny bubble, right? what this is trying to show |
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14:37 | There are other types of proteins that discovered since. And so the class |
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14:42 | collectively referred to as the, all . And they basically coat the plasma |
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14:48 | and bend it to its will. right. So, Clarin isn't the |
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14:52 | one and part of the the the of naming these different types of processes |
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14:57 | endocytosis and exocytosis is kind of dependent the presence of which proteins are |
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15:03 | All right. We're not, don't about that so much. All |
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15:05 | But the idea here is that these are there to create the vesicles to |
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15:13 | them to bend so that you can the membrane to turn into that |
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15:19 | All right. Not so bad. how I get my vesicle, that |
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15:22 | that go someplace where does it And why does it go? Do |
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15:28 | just kind of float around the inside the cell randomly when I went to |
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15:33 | ? They did, right. They went where they kind of went. |
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15:39 | the thing is is that everything in cell has a direction, has a |
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15:44 | and is doing something. It's not it in a non random fashion. |
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15:48 | right, there are molecules called the and the snaps. All right, |
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15:54 | snares are molecules that are associated with vesicle and the molecules that are associated |
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16:01 | the membrane that serve as a way the two to recognize each other. |
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16:06 | other words, it's a way to molecules to or vesicles to the |
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16:11 | So the vesicles nowhere to go. ? So if I'm trying to secrete |
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16:16 | the lumen of the digestive tract that vesicle isn't just wandering around the |
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16:21 | going, I don't know where to . Maybe I'll go down here to |
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16:23 | basal side and release myself out into actual body, which would be a |
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16:28 | thing. Instead, what it's doing it's being directed to the apical surface |
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16:33 | there is a dock for it to and wait to be told. Remember |
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16:36 | I said the regulatory portion, the is like, OK, I want |
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16:40 | to go hang out here until we you to release your stuff. And |
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16:43 | what this is not a great picture you. It's gonna be here in |
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16:46 | a second. I'll show you. right. The purpose of the other |
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16:50 | is the, the snap is to everything has been released, I want |
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16:54 | recycle everything. So basically, it a dissociation of these snare molecules. |
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17:00 | , there are V snaps and T . Just think V for vesical T |
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17:04 | target, that's the easy way to it. And all this stuff costs |
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17:08 | . So moving things in cells cost . Uh I thought I had a |
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17:14 | showing the snares and snaps. I it's when we do the synapse that |
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17:18 | show this a little bit more All right, because one of the |
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17:23 | that it does is that the they don't just come and hang out |
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17:27 | the membrane like this, they actually emerge with it. So they're not |
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17:32 | , they're not closed there, half half. And so that's what they're |
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17:36 | for is that signal, we'll get that again, eventually we'll get to |
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17:40 | . So if are you with Yeah. Mhm And the membrane has |
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17:49 | , right? So the ones that snares are there. They have the |
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17:53 | for the V snares and V snares the T snares. And again, |
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17:57 | purpose here is just like a dock a boat, right? The boat |
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18:00 | find the dock. But if you tie it off, it's just gonna |
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18:04 | around. And so that's kind of idea here is that they basically come |
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18:07 | and they lock in place. So that vesicle can't move anywhere, I |
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18:12 | I, again, I may have , let me just see. |
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18:15 | I thought I had a picture maybe or three. We're gonna look at |
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18:19 | when we talk about the synapse in couple of lectures, we're gonna look |
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18:21 | the neuromuscular junction as an image and neuromuscular junction is a perfect example of |
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18:27 | because between the neuron and your there are thousands upon thousands of bests |
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18:34 | pre lined up ready to go so you can do this, right? |
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18:38 | don't have to, oh, we to make up the vesicles with full |
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18:41 | the neurotransmitter. Tell the muscle what do. It's they're ready to |
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18:45 | right? So let's just kind of this down, endocytosis, exocytosis |
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18:52 | and um pinocytosis, I think we're , yeah, here we go. |
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18:56 | , the different forms of endocytosis is first thing. So how we're bringing |
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19:00 | in notice on this list here, is kept aside. All right. |
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19:04 | we're gonna look at endocytosis and phagocytosis I think we have exocytosis or maybe |
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19:08 | was what I was already referring to is just how we release the materials |
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19:14 | the cell. Now, it's all scary. All right. First pinocytosis |
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19:25 | back in the day. So I'm of giving you why we name things |
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19:29 | . You know, they saw macrophages things that, you know, that |
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19:31 | around. So they call that, literally means cell eating. All |
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19:35 | that's the next slide, right? then what they noticed is that cells |
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19:39 | actually have this imagination and the cell would come along and they would just |
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19:44 | of enclose around a portion of of the extracellular fluid that was kind |
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19:48 | around the cell was, you just like a little pinch off, |
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19:52 | ? And they would say, what is causing it? Well, |
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19:54 | is nothing there causing it's what basically it is doing, it's picking up |
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19:57 | water and whatever happens to be in environment in that water at that |
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20:01 | So if we have eating, we have drinking. So pinocytosis is basically |
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20:08 | drinking and it's very nonspecific. So not actively going. Oh, this |
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20:14 | the stuff that I want. It's this area. So I'm bringing it |
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20:17 | , it's basically just bringing in a of the materials and the extracellular fluid |
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20:21 | a vesicle and then whatever the cell out of that, it will uh |
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20:25 | and destroy whatever it doesn't need, will then secrete out later. |
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20:29 | So that's basic. Typically, when think, we think that the |
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20:35 | as I said, doesn't do things . It's actually actively seeking to grab |
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20:41 | . And so here what you're gonna is you're gonna have receptors on the |
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20:44 | of the cell. Things are gonna binding to those receptors that when you |
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20:48 | that receptor, it's gonna trans locate a region of clain or some |
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20:53 | And basically say, hey, I up what we're looking for and once |
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20:56 | get enough of the things bound up that, that's gonna activate the clan |
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20:59 | cause it, that imagination to fold . And then now you've created that |
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21:03 | for endocytosis. All right. So call that receptor mediated because a receptor |
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21:08 | involved and it's specific for the thing you're hunting for that makes sense versus |
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21:15 | , which is like, well, we grab or grab. All |
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21:19 | So for example, I see the, the furrow brow and it's |
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21:22 | . If you have a fur I can usually read that in the |
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21:24 | . But if everyone's staring at me this, it's really concerning. All |
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21:28 | . So for example, there is specific molecule x that the cell is |
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21:33 | to bring in for the purposes of from the environment or maybe they're using |
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21:37 | as a way to transport across to other side. So like for |
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21:42 | between the bloodstream and the brain, example. So what it would do |
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21:47 | like, OK, I'm binding things and once I get enough things bound |
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21:50 | , I'm gonna create my vesicle, I move the vesicle over and then |
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21:54 | do exocytosis on the other side. right. That would be an |
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21:58 | All right. Then we have caviar endocytosis, which is called potocytosis. |
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22:04 | is where they started noticing the different of cot um this was noticed uh |
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22:10 | in the vasculature. So in the I just gave right, it would |
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22:14 | like, oh I'm pinching off and , I'm creating a vesicle. The |
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22:19 | is I'm not using Clarin, I'm a different type of Coomer and this |
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22:22 | why it was distinguished as something unique different. All right. And |
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22:27 | trying to move things across uh the because you're too big to leak through |
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22:33 | be an example. So the vasculature very, very thin and you basically |
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22:37 | transporting things quickly across. All So do those three kind of make |
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22:43 | or do you need a better? , ma'am. So, potocytosis would |
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22:51 | be the the first one that we , we we would say is |
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22:56 | The others are primarily using Clan. again, probably when you're standing up |
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23:01 | or working on somebody digging your fingers somebody, we may have found out |
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23:06 | there's actually more to it than All right, if you go on |
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23:13 | , you get to watch fun videos phagocytosis. All right. So the |
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23:16 | here with phagocytosis and endocytosis. endocytosis, remember you have a flat |
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23:22 | that is invaginated, right? it's going downward and then closing |
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23:28 | Phagocytosis is targeted towards the thing that trying to destroy. But notice what |
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23:33 | cell is doing is it invaginated its and it's reaching out, isn't |
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23:39 | And these are really like I they are cool videos on youtube that |
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23:42 | can watch, just look up neutrophil bacteria. That would be an easy |
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23:46 | . And you'll get to watch it the neutrophil is actually chasing the bacteria |
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23:50 | . And then finally, you see , it actually reaches out, extends |
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23:54 | cytoplasm creates these proto extensions, They're not really arms, it's just |
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23:59 | reorganization of the act in it reaches and then encloses the thing that it's |
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24:05 | to consume. And so it encloses in a vesicle and then you can |
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24:09 | that vesicle and then merge it with lysosome and just, you know, |
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24:13 | those enzymes to break down whatever it that you've engulfed. So that's |
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24:18 | So it literally is, looks like grabbing something and, and eating it |
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24:22 | . All right. Again, all these require a TP. Um This |
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24:31 | an example to show you this process uh using a Lyo. It's not |
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24:39 | great example, but it's showing you you can recycle using this Clarin. |
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24:45 | so here you can see we got over here. Here's an Endo, |
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24:51 | endo is simply the fancy word for vesicle that you've brought into the |
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24:56 | right? So Endo is the same as a, what would it be |
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24:59 | faga zone? What do you It's an endo that I just created |
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25:07 | cytosis? So, an endos is the vesical that I brought in. |
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25:12 | so I'm gonna digest things here. how am I gonna digest? I |
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25:16 | to merge with the Lycos. You remember what lysosomes do, right? |
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25:19 | all took our bio one. We our cell, right? It's a |
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25:23 | of enzymes. Merge Lyo with an those enzymes now destroy whatever is |
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25:28 | But you know what um there are for some of the molecules and I |
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25:33 | to recycle those so I can use classroom to form and then I've used |
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25:38 | cla in to pinch off and use classroom to reform and I can just |
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25:41 | back and forth over and over creating lysosomes over and over again. |
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25:47 | kind of cool. It kind of sense. So this process is specific |
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25:52 | it's recyclable. Is that a good ? Good work, bad work. |
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26:00 | . How do we feel about vesicular , endocytosis? Thumb up. I |
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26:06 | that more of those and then we're ready for this one. Everyone know |
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26:14 | osmosis is. If I gave you test question about what is osmosis? |
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26:18 | now, could you all answer it your entire human phys grade dependent upon |
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26:22 | definition of osmosis and your explanation of ? Are you confident that you could |
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26:26 | an a and go on and practice ? Some people are going. |
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26:32 | of course. So I should just ahead and skip it then. |
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26:35 | no. All right. The reason say that is because over the course |
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26:40 | your academic career, you've probably been multiple definitions, right? Every year |
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26:43 | have to learn it and you sit and memorize it for the test. |
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26:46 | vomit the answer out right. Here's and then you promptly go. I'm |
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26:51 | really sure. I understand this. sound about right. OK. My |
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26:57 | today is to make osmosis simple. right. So you're ready for the |
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27:02 | answer. If you have this you'll never go wrong. Don't let |
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27:06 | chemists confuse you. What do chemists care about? Do they care about |
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27:10 | ? No. What do they care the stuff in the water? |
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27:13 | The solutes, right? So whenever give you a definition, they're talking |
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27:16 | solute concentrations, right? And what's to the water with all these solute |
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27:22 | ? And it's confusing, especially on test when you're like under pressure and |
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27:26 | got 38 seconds to answer this All right. So throw all that |
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27:30 | away. Let's keep it simple water osmosis is the diffusion of water down |
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27:34 | gradient that's all it is. If have high water concentration, low water |
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27:38 | , which way is water gonna it's gonna go down its gradient. |
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27:41 | at the end we can move on knowing that it's not that simple, |
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27:47 | ? That we're not just looking at , we're looking at water plus other |
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27:51 | , we need to consider the solute well. So if I have 100% |
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27:54 | , how much solute do I 0%? If I have 50% |
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27:59 | how much solute do I have? see if you keep it with that |
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28:04 | mind, like I'm always dealing with is my water percentage? You don't |
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28:09 | to worry about anything else, So they can throw all sorts of |
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28:13 | at you to make you feel confused like, you know, you have |
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28:17 | much sodium and this stuff all you do is ask the question is all |
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28:20 | , what is my water percentage? I know I have more water over |
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28:22 | and less water over there, water gonna move in that direction as long |
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28:26 | there is no barrier that prevents the of water. OK. So, |
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|
28:31 | far you're good with me, So when a membrane is permeable to |
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|
28:35 | , it allows water to move if impermeable to a solute, solute doesn't |
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|
28:38 | . So water is gonna continue to down its gradient until it reaches its |
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|
28:43 | pressure. That's why I throw everybody . Osmotic pressure. You remember osmotic |
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|
28:50 | ? What is the definition of osmotic ? You wanna know? Mhm. |
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|
28:58 | , that's technical. And I'm not it could be. Right. I |
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|
29:02 | know. I, I, but , it's hard. Right. All |
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|
29:05 | . So every fluid has its own . Hold up your water bottle real |
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|
29:11 | . Is the water escaping? See, water, water is the |
|
|
29:13 | escaping from those things? No. ? Because the water pressure on the |
|
|
29:19 | , you can put them down. water pressure on the inside cannot overcome |
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|
29:23 | internal pressure of the plastic holding it the moment that the internal pressure overcomes |
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|
29:29 | outward pressure, water flows out. ? So that pressure that that fluid |
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|
29:33 | , whether it be the big the small jug or my tea sitting |
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|
29:36 | here, there is a hydrostatic right? Hydrostatic, the water |
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|
29:42 | All right. Now, if I a container that's 100% fluid and 50 |
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|
29:50 | 100% water and 50% water, each those do they have hydrostatic pressures to |
|
|
29:55 | ? Yes. And so as water from the 100% to the 50% what's |
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|
30:00 | to the pressure over here? Hydrostatic is going up, what's happening to |
|
|
30:04 | pressure over here? It's going There's gonna be a point where the |
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|
30:08 | become equal so that water molecule that's to move over when both those pressures |
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30:14 | equal, it's gonna come over and gonna be uh uh there's too much |
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30:17 | over here. You got to go or you have to kick another one |
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30:19 | out. And so you now have that point where those two pressures are |
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|
30:25 | is called the osmotic pressure. All , let me give you a |
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|
30:31 | Do you guys know what a smart is? Yes. You guys know |
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|
30:37 | smart car over here. OK. many people can you fit in a |
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|
30:40 | car? I heard 43. All . You guys are going clubbing tonight |
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|
30:49 | you have eight friends. I didn't , can you fit eight people |
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|
30:55 | I asked the question, how many can you fit in a smart |
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|
30:58 | Right? You could probably get about , right? But let's say you |
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31:01 | that ninth person and you shove them there. What's gonna happen on the |
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31:04 | side? Someone's gonna pop out, reach the pressure point that is like |
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31:10 | osmotic pressure for the car. It's osmotic pressure because it's not water. |
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|
31:13 | that's the kind of the same principle . Water will continue to move down |
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|
31:18 | concentration gradient until the pressure to where going opposes its movement. That's the |
|
|
31:25 | . That's osmotic pressure. Isn't that ? Isn't that so much easier than |
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|
31:31 | sort of strange explanation with solute concentrations stuff like that? Yeah. |
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|
31:37 | So when the chemists try to confuse just go no water concentration, |
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|
31:42 | osmotic pressure. Ah No, no simple it's the opposing pressure that |
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|
31:48 | the movement of water. That's all is. So, osmolarity is what |
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|
31:54 | concern ourselves with in biology or really physiology. You know, you get |
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|
31:59 | learn all about molar and stuff, we never talk about osmolarity or do |
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32:02 | guys ever talk about that in like ? No, no. OK. |
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32:07 | this is a new term. So osmo, it's dealing with solute. |
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32:11 | for example, what it does, , I shouldn't give you the |
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32:14 | The definition simply it describes the number particles in a solution. It doesn't |
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32:19 | what the particles are. It just the question, how many are |
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|
32:24 | So if I have like 100% sodium , right? And so I'm like |
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|
32:28 | one mole of sodium chloride. And I drop that into a fluid, |
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|
32:31 | still have a mole of sodium don't I? Right? But I |
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|
32:37 | have sodium and chlorine that are dissociating their respective ions. So I don't |
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|
32:43 | one molecule, I have two particles each sodium chloride. So my osmolarity |
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|
32:50 | two osmoles if that makes sense. if your molar, so you |
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|
32:56 | one mole in a liter is one , right? When you're dealing with |
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|
33:02 | something like sodium chloride that dissociates, would become two particles. So that's |
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|
33:07 | os moles per liter. All That makes sense. So it's counting |
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|
33:13 | number of particles. It does not what the particles actually are and that's |
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|
33:17 | your body is watching, right? when you become thirsty, the reason |
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|
33:23 | thirsty is that your osmolarity has right? And your body wants to |
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|
33:28 | it back up to the proper solute balance or concentrations. All |
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|
33:35 | So our concern is then what does and solute do in the body when |
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|
33:43 | change waters, solute concentrations? All . And again, the other example |
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|
33:50 | have up here is glucose, glucose dissociate. It just goes in the |
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33:53 | and it sits there. So one of glucose would still be one |
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|
33:57 | All right. I'm not gonna make do math just so you know, |
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|
34:00 | you ask the question, if you a math equation, I know I |
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|
34:02 | said it once just reinforcing, there's gonna be math on the test. |
|
|
34:08 | right. No equation balancing figure. chemist taught you all that stuff. |
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|
34:14 | I want to show you here is first, just a couple of, |
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|
34:17 | , of scenarios when we're dealing with and salt. All right. So |
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|
34:21 | the left here, what you're looking is you're looking at a picture of |
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|
34:24 | normal cell under normal conditions and we're a whole bunch of stuff. We're |
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|
34:27 | looking at the sodium potassium pump, looking at sodium leak channels and we're |
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|
34:31 | at chlorine and the anion accelerate. not even showing the anti Oh |
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|
34:36 | it is. There. It All right. And this is what |
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|
34:38 | see in a normal cell under normal . So the concentration of potassium is |
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|
34:43 | high on the outside. Sodium is . Lots of an cellular proteins. |
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34:47 | is is fairly low on the And you can see we've got pumps |
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34:50 | are active that are moving sodium and to create that imbalance of of |
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|
34:56 | right. Chlorine is moving in the of of where there is positive |
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35:02 | It's just following along. And then cell, your proteins are stuck on |
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35:06 | inside and to keep everything nice and water is moving in and out so |
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35:09 | you have your normal happy cell. . That's a normal circumstance. All |
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|
35:15 | . If we treat this normal happy with this chemical called, do you |
|
|
35:19 | it's horrible smelling up there. When I first learned about it, |
|
|
35:22 | thought it started with a W-2. right. So Waban kills the sodium |
|
|
35:28 | pump. All right. So you're longer able to pump. And so |
|
|
35:31 | that happens, ions are gonna move their concentration gradients to reach equilibrium. |
|
|
35:36 | that's what this uh right side image trying to show you is that we're |
|
|
35:39 | to reach an equilibrium. All And when that happens, what's uh |
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|
35:44 | amount of ion on the inside, as a function of those, the |
|
|
35:49 | of the proteins is gonna draw water the cell. And when you draw |
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35:53 | into the cell, what you're doing you're dropping the osmolarity inside the |
|
|
35:58 | right? In other words, there's water, the cell swells up and |
|
|
36:02 | you've created an environment that's not conducive the chemical reactions that would normally take |
|
|
36:07 | in the cell. So when cells , that's bad. Ok. So |
|
|
36:14 | does this body deal with this right , in this condition? What we're |
|
|
36:17 | is we're giving it a poison. what is, it's literally creating a |
|
|
36:22 | . All right. So it's killing cell and that it's done, |
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|
36:27 | But under normal circumstances, the body how to maintain based on how it |
|
|
36:33 | the inside of the cell relative to outside of the cell. So there's |
|
|
36:36 | , this a whole bunch of mechanisms your body that we're going to explore |
|
|
36:41 | during the renal system stuff that is for ensuring that you have the right |
|
|
36:45 | of water and the right amount of in your body so that your cells |
|
|
36:49 | normally. But let me just kind show you what's going on here. |
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|
36:52 | your normal osmolarity throughout your entire except for one place which we'll ignore |
|
|
36:56 | right now is roughly 300 million All right, no matter where you |
|
|
37:01 | , just one place is different and gonna ignore that. Now, |
|
|
37:04 | it's 290 but 290 is a horrible to work with. So 300 is |
|
|
37:08 | we're gonna stick with. Ok. you can see in this top |
|
|
37:11 | look, we got everything in everything is in balance. And then |
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|
37:14 | we're gonna do is we're going to a whole bunch of solute here on |
|
|
37:18 | outside, right? So the osmolarity . So when that happens, when |
|
|
37:25 | added solute on the outside, in , we have diluted the outside, |
|
|
37:31 | we? Right. If I was solute now I've turned into 70% |
|
|
37:35 | I've gone from 50% water to like water, right? So that's the |
|
|
37:41 | thing that the chemist confuse us about they talk about solutes and they ignore |
|
|
37:45 | . So here, what I've done I've increased the amount of solute or |
|
|
37:49 | the amount of water on the So what does water do? It |
|
|
37:53 | outside? And when that water leaves cell, it causes the cell to |
|
|
37:56 | . Now, the inside of the has a greater osmolarity. And when |
|
|
38:01 | change the osmolarity inside the cell, cell becomes nonfunctional. It doesn't, |
|
|
38:05 | not creating the environment to allow the to work inside the cell. The |
|
|
38:10 | is failing. So what does it ? It introduces these co transporters, |
|
|
38:17 | exchangers to the cell surface so that can then move ions around so that |
|
|
38:24 | is brought back into the cell so we can create an equilibrium when you |
|
|
38:31 | that equilibrium. Now, the cell able to function water salt balance |
|
|
38:38 | Similarly, we can do the same . If we decrease the os outside |
|
|
38:42 | comes in cell swells up. We pumps and channels in places to pull |
|
|
38:47 | out of the cell. So water . I think this is the place |
|
|
38:52 | may be wrong where I give you better example of this. You're |
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|
38:57 | what do you mean? Well, I've been doing this for so long |
|
|
38:59 | keep you the same examples over and again. Do you guys remember high |
|
|
39:04 | ? Did high school suck or? it awesome? It sucks. |
|
|
39:08 | When people answer that question, it me which group you're in, |
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|
39:13 | I mean, you know, the I'm talking about, right? Every |
|
|
39:16 | school has the groups, right? you have the popular group? Like |
|
|
39:20 | prom queen? You know, you have that. Um, people are |
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|
39:23 | in their head like, you you have the, the one girl |
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|
39:29 | everyone wants to date or wants to , you have the guy that's dating |
|
|
39:34 | girl, right? You have the that's the best friend of the |
|
|
39:43 | You know, he's kind of trying , you know, be, he's |
|
|
39:45 | that friend zone, right? He's to, you know, when he |
|
|
39:48 | away, I'm right there to, pick everything up. I'll be the |
|
|
39:52 | , you know, this one and they have their group of friends that |
|
|
39:55 | of hang out with them, watch things for a little bit. You |
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|
39:58 | see them there. I don't But every school has that and if |
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|
40:03 | going, no, it doesn't trust . It did. You were probably |
|
|
40:07 | girl. All right. Now, , why bring this up? Your |
|
|
40:13 | are high school politics. All Sodium is the girl. The popular |
|
|
40:22 | . Sodium loves to hang out with . Water loves to hang out with |
|
|
40:26 | . Wherever sodium goes, water Sodium and water. Take the same |
|
|
40:31 | when one goes to the restroom, other one follows but there's an impermeable |
|
|
40:36 | there. So water has to wait . Water is the guy in the |
|
|
40:40 | , right? He's the cool quarterback or whatever they are the couple in |
|
|
40:45 | . So a sodium goes water All right. Chlorine is the one |
|
|
40:51 | trying to weasel in on water's He's just waiting for water and sodium |
|
|
40:56 | break up. And so when sodium and hangs out, chlorine goes, |
|
|
41:02 | sodium goes. Yeah, water is . But you know, I'm on |
|
|
41:06 | fringes and then wherever sodium and water , all their friends go worse. |
|
|
41:10 | wherever water goes because he's the cool . Potassium follows wherever sodium goes, |
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|
41:16 | goes, wherever water goes, all the other ions follow because they follow |
|
|
41:23 | and then remember waterfall of sodium. you remember that if you ever get |
|
|
41:28 | , just go. Oh yeah. school politics. All right. And |
|
|
41:35 | what you're seeing here is basically I'm these ions. Why? Because water |
|
|
41:42 | gonna go and hang out wherever sodium . That's what's really going on |
|
|
41:47 | Now, we have some weird friends that group. You know, the |
|
|
41:52 | Jock guy always has that one friend not particularly bright. A little |
|
|
41:57 | Right. But eventually we'll get things . That's right. Is our slow |
|
|
42:04 | . So wherever water goes, urea , but it takes a sweet time |
|
|
42:09 | get there. All right. And what this is trying to demonstrate. |
|
|
42:13 | Urea uh is like, oh, water, water goes, Urea and |
|
|
42:16 | Urea goes, oh, wait a . I need to go back the |
|
|
42:18 | direction to balance things out. And it does. And it's actually one |
|
|
42:22 | the things that the kidney has to up with is that it's constantly moving |
|
|
42:26 | e and then kind of goes. . Well, you know, I'm |
|
|
42:28 | go back this direction and it, only get rid of about half the |
|
|
42:31 | , your body is trying to get of at any given time because of |
|
|
42:34 | it slowly moves down its gradients. water salt movement is going to be |
|
|
42:45 | upon that balance, that osmolality or osmolarity of the body. So far |
|
|
42:50 | me, you're like, I'm not anyone here. Not sure. |
|
|
42:57 | Now, let's see how this actually to your lives, right? So |
|
|
43:04 | is something that if you're planning on health profession is something that you need |
|
|
43:07 | understand. All right, and it with this question of osmolarity because what |
|
|
43:12 | dealing with is uh solutions for the part, right? So if you |
|
|
43:17 | a hypertonic solution, it's also referred as being hyper osm. Um And |
|
|
43:22 | that would basically say hyper iso you already know that prefix what it |
|
|
43:26 | . It's the suffix, the tonic referring to the solute and this is |
|
|
43:31 | we get kicked in the pants again those crazy chemists because they don't care |
|
|
43:36 | the water and most of the stuff put in our body, we're not |
|
|
43:39 | about the water we're carrying what we're in, right? So you guys |
|
|
43:43 | here ever used Visine because you have eyes, right? One person is |
|
|
43:48 | their head. Two OK. Three . The rest of you need to |
|
|
43:52 | out outside for a little bit longer stare at your screens for a while |
|
|
43:56 | eyes will start feeling and what do do you put via in Ive is |
|
|
43:59 | isotonic solution, right? Iso meaning solute concentration as your tears. So |
|
|
44:09 | just adding fluid but it's not affecting tenacity of the tears themselves. |
|
|
44:18 | when we're talking about our bodies, the most part, we're talking about |
|
|
44:22 | in osmolarity or osmolality, right? most common causes I mentioned the sodium |
|
|
44:27 | sodium goes, water follows and glucose play a role as well. So |
|
|
44:32 | when you eat food basically, it's water to wherever the glucose is. |
|
|
44:36 | then when glucose starts moving around the , that's when you're drawing water into |
|
|
44:41 | blood to kind of dilute out the . But once you move into the |
|
|
44:43 | , water goes to where the cells . I'm gonna show you the effects |
|
|
44:49 | these things. And I want you see if you can predict why. |
|
|
44:52 | here what we're doing is we're you can see this is ECF and |
|
|
44:56 | F. All right. So, what we're gonna do is we are |
|
|
45:00 | or injecting into our person here, liters of uh basically same osmo. |
|
|
45:08 | it's isotonic saline. All right. you can see here, I started |
|
|
45:11 | , you can see osmolarity is 2 90. So you can see if |
|
|
45:16 | inject 1.5 liters of fluid into the fluid, I get swelling in the |
|
|
45:21 | fluid, but I don't see any in the uh intracellular fluid. Why |
|
|
45:25 | that be? Why do you think would be not that it's impermeable because |
|
|
45:32 | has water. That would be a guess. OK. It's impermeable but |
|
|
45:36 | know it's not because plas membranes are to water. So why do you |
|
|
45:42 | same osmolality? Right? Because it's I've injected in and there's no change |
|
|
45:48 | the osmolality. So there's nothing drawing in or out, right? That's |
|
|
45:53 | key thing that you need to Is water being drawn in a particular |
|
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45:57 | . When I see osmoles, I to be doing that. Ok. |
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46:00 | let's see what happens when we add water to a system. Here we |
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46:04 | up at the top. There's your . You can see same osmolality. |
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46:07 | . I added 1.5 liters of pure onto the ECF and you can see |
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46:12 | I get initial swelling because whenever I anything in anything, it's initially going |
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46:16 | swell up. But look what happens time. Does it balance out? |
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46:25 | , it starts moving over into the fluid so that you get not equivalent |
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46:29 | but you get balance in terms of that fluid is gonna go. All |
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46:36 | , now, why should this be , really important to you? All |
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46:40 | , you have a friend who's right? And you being an entrepreneur |
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46:46 | not entrepreneuring, but you know, anxious young pre health student, you're |
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46:50 | , oh, I've been learning how inject people with ivs. Let me |
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46:53 | you an IV of pure water. know what's gonna happen? That's what |
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47:00 | is right here, right? I'm water into the extracellular fluid. Where |
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47:04 | it going into the cells? And you add too much water into the |
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47:11 | , they, and now you have person who has no red blood cells |
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47:18 | carry oxygen, drowns in their own . So when you're dehydrated, if |
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47:26 | here and here working in the usually get one or two, you |
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47:29 | one. So what do you give sailing? But sailing makes me |
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47:36 | Yeah. But it keeps the cells exploding, but I'm giving them water |
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47:39 | the same time and it will eventually itself out. Ok. Lactated |
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47:46 | D five LR. All right. an impossible situation. You get a |
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47:53 | of pure sodium chloride. No jam it into their extracellular fluid. |
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47:59 | doesn't sound like a lot of Does it? What do you expect |
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48:02 | happen? All right. There's no in the fluid because remember there's no |
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48:08 | , right? But what did I do as I changed the osmolarity? |
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48:11 | see it went from 290 to 3 . So where is the water gonna |
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48:17 | ? It's gonna go down its concentration until it reaches equilibrium, right? |
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48:23 | so we get swelling on both sides the membrane, right? That's the |
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48:30 | . So the the principle to carry from this is that water is gonna |
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48:35 | down its concentration gradient. It's gonna where there's extra solute, which is |
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48:42 | the chemists talk about and your body trying to balance out and trying to |
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48:47 | you as close to 300 mil osmoles it can. Despite the fact that |
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48:52 | live in Houston and you're sweating all water out of your body, |
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48:56 | Despite that, we're not putting a of solute and water into our |
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49:00 | It's always doing that. And so we consider any thing, when it |
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49:05 | to electrical, when it comes to this stuff, we have to ask |
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49:08 | question of water, salt and that's our body spent a lot of time |
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49:14 | this stuff. Does this kind of sense? Iiii I think I explained |
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49:22 | well enough. I don't know, I didn't. They're all staring at |
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49:27 | like you have no idea what I . OK, because you're doing this |
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49:33 | , but I think you're cold. . Questions. All right. So |
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49:45 | way that we move things through a . So like when you go |
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49:49 | go to Taco Bell or whatever, you're trying to do is you're trying |
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49:52 | get materials from outside your body into body, even though you don't think |
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49:56 | the digestive system being outside the It is, it's just a tube |
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50:00 | happens to travel through your body like whole throat doughnut, right? That's |
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50:04 | the external surface. And so what trying to do is you're trying to |
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50:07 | things from the external circle to the parts of the body. So that |
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50:10 | it has to has to cross over . So what we refer to as |
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50:15 | movement is what is called epithelial And there are two different types, |
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50:21 | ? I can move through a All right. That would be trans |
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50:26 | self uh transport or I can be the cells which is not that |
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50:33 | you're gonna see that less often, that would be paracellular transport. That'd |
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50:37 | leaking through the leaky junctions or the tight junctions, the leaky tight |
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50:42 | , you guys learned about tight right? Ok. All right. |
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50:46 | , if I'm moving from the, hollow portion of an organ, all |
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50:52 | , what I'm doing is I'm absorbing the body. And if I'm moving |
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50:57 | the body across the cell into that , that's secretion. And what I |
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51:02 | have up here is a definition of I'm leaving the body altogether, that's |
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51:06 | , right? So when you're making , that is secretion and then when |
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51:10 | pee urine out that's excretion, You sweat, that's excretion. |
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51:17 | Now, one of the key things when you're dealing with epithelial transport is |
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51:23 | have two plasma membranes that you have cross and we have different concentrations of |
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51:29 | ions on either sides of those So either you're going to have to |
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51:34 | uphill to get into the cell and you're inside the cell, then you |
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51:38 | have a high concentration. So then gonna go downhill, right? So |
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51:42 | an uphill on a downhill or you're into the cell which would be downhill |
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51:46 | then you have to be pumped out other side if that makes sense. |
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51:50 | there's always going to be an uphill there's always gonna be a downhill, |
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51:52 | never going fully downhill across both membranes fully uphill both membranes. All |
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51:57 | And so this is what this is of showing you here. But we |
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|
52:00 | a couple of examples so that you kind of see here. So in |
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52:03 | the first example, you can see talking about sodium sodium, remember we |
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52:06 | lots of sodium outside the cell, little sodium inside the cell. So |
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52:10 | from the loin into the cell is to be a passive event. It |
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52:14 | require energy. Sodium comes in and I don't want the sodium inside the |
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52:18 | . So what do I have to ? Pump it out? So I |
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52:21 | a pump to do so. All , I've got lots of potassium inside |
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52:26 | cell. Why? Because I'm pumping in. So what it's gonna do |
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52:28 | it's going to leak out the But if I'm trying to secrete |
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52:32 | I just introduce those types of channels here on the lumen. So even |
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52:36 | I'm pumping potassium in out, it ok. So it can go in |
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52:41 | direction but it's going out of the . What about glucose? Well, |
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52:45 | remember what we said about glucose, , there's lots of glucose inside |
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52:49 | So in order for me to get the cell, what do I need |
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52:51 | get inside the cell cot transporter? ? So here's our sodium glucose co |
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52:58 | transporter. Glucose goes in the It gets pumped out of the |
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53:02 | Sodium does what about glucose itself? , now I'm going downhill because I |
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53:05 | have glucose freely running around my That's a waste of glucose. |
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53:10 | what do I have is I have transporter so it just binds it up |
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53:14 | sends it out into the blood or into the intertrial fluid gets picked up |
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53:17 | the blood and then moved off to it needs to go. This would |
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53:20 | an example. What's the last one ? oh yeah, chlorine secretion. |
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53:25 | , I'm using that NKCC to move into the cell. I'm using the |
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53:31 | as the driver of that, that energy and then I have a |
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53:36 | So I'm moving chlorine up against its and I'm secreting chlorine out down its |
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53:41 | . So you see half is half is down which one comes first |
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53:46 | upon which thing you're looking at. right. So what this does is |
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53:56 | us to transition away from moving things the membrane to talking about how cells |
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54:02 | to each other, right? Self communication. Now, I hate that |
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54:12 | book says this and I'm just gonna it this way, almost 100% of |
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54:16 | communication between cells is through chemical There's some rare exception that it's |
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54:22 | but even when we talk about we think of neurons being electrical, |
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54:27 | really chemical, right? They use aspects of signaling, but they're not |
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54:32 | doing electrical signaling. When you're talking electrical signaling, what you're doing is |
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54:35 | changing the cell membrane um and you're a discharge. In other words, |
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54:40 | are moving in and out and you're a signal along the surface through the |
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54:44 | of these ions. When you're dealing chemical messages, what you're dealing with |
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54:48 | some sort of molecule that's being released the cell and then another cell binding |
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54:52 | that molecule. So there are four methods. We can do gap junctions |
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54:57 | would be a form of electrical then contact dependent local signaling and long |
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55:02 | or hormone signaling. And I just to kind of walk through these. |
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55:05 | I'm gonna show you some very specific that you can use to help you |
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55:09 | , conceptually what we're dealing with. this is the gap junctions. This |
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55:13 | another term for this would be Jurin you're if you're juxtaposed to somebody, |
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55:19 | are you right next to? So juicy signaling is a term that |
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55:25 | to two cells touching each other or in contact with each other talking to |
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55:30 | other. So this upper picture right through the gap junction is an example |
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55:34 | of electrical signaling, the ions are between the cells. So the cell |
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55:40 | communicating through some sort of chemical what it's doing is it's having an |
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55:44 | exchange. And so a current is from cell to cell to cell. |
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55:50 | , what is a gap junction? , it's a bunch of proteins that |
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55:54 | the an open pore, these proteins called connections. There's multiple ones and |
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55:59 | very, very small, they allow the movement of small molecules. Contact |
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56:06 | signaling is a little interesting. All , it's another type and this is |
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56:10 | chemical form of signaling. And this when two cells come into contact with |
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56:13 | other. One has a cell surface that is a receptor. The other |
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56:18 | has a cell surface protein that is lien. And when they come into |
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56:22 | with each other, then the one the lien is telling the one with |
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56:26 | receptor what to do. We usually to these types of molecules as cams |
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56:30 | cell adhesion molecules. So like the system uses this form of communication. |
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56:36 | have one immune cell, another immune that come into contact with each |
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56:39 | they touch each other and they use leg and receptor binding to tell the |
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56:44 | with the receptor how to respond to sort of immuno, basically immuno |
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56:50 | All right. But this isn't the type of cell to cell recognition. |
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56:53 | are other cells that do this as . All right. This type of |
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57:00 | is what you're more familiar with. right. So we have a dorine |
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57:04 | . This is a cell talking to . Do you ever talk to |
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57:08 | Do you write yourself notes, reminders , what to do? That's in |
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57:12 | , what it's doing is that it out a signal that then comes bind |
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57:16 | and binds to a receptor on the to actually regulate what's going on inside |
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57:19 | cell. Right. Kind of like reminding yourself, you know, I |
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57:24 | to do this and you just create to do list. It's kind of |
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57:26 | same sort of thing. So it's talking. All right, paracrine, |
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57:31 | the other hand, is nearby, next to but nearby signaling. All |
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57:37 | . So if I'm re releasing a , it's that signal is a chemical |
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57:43 | traveling out and cells that are nearby can pick up and respond to |
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57:46 | As long as you have the right . If you don't have the right |
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57:49 | , you're never going to respond. we just ignore those. OK? |
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57:53 | here, it's not touching. If touching, that's still x. |
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57:59 | So that's the kind of the key . There has to be a direct |
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58:02 | , a direct interaction. All Um So the material is traveling some |
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58:09 | of distance. So even though these cells are like near each other, |
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58:13 | not touching each other, that's why not Jurin. So like a synapse |
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58:18 | be a form of paracrine signaling, Jurin because they're not touching the cells |
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58:23 | are not interacting. All right. other thing I would say is that |
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58:27 | this uh this signaling molecule leaves, has a finite distance, it can |
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58:32 | because of enzymes in the body and mechanisms that remove the signal itself. |
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58:37 | these are not particularly long distance autocrine, obviously, you're self |
|
|
58:43 | but with paracrine, you're not, not like you're reaching out to the |
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58:46 | side of the room or the other of the body. It's like just |
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|
58:49 | area right here. Think about being by a bee, right? You |
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|
58:52 | local eye swelling, you don't get everywhere. This last is long distance |
|
|
58:59 | . There's no book or no picture any book that does a good picture |
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|
59:03 | this. But the idea is that is a blood vessel traveling some distance |
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59:07 | the body. So here are the that are releasing their chemical, that |
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59:11 | goes into the bloodstream, it travels distance away to the cells that have |
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59:15 | right receptors and you get a right? This is what hormones |
|
|
59:20 | All right, this is the endocrine . So long distance signaling falls into |
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59:24 | category. All right, we refer this when uh the signal goes into |
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|
59:29 | bloodstream, we refer to it as hormone hormones have varying sizes and uh |
|
|
59:34 | which will cover it, I think the next lecture. But the idea |
|
|
59:38 | is I'm using one part of my to tell another part of my body |
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|
59:42 | probably more than just one what to . Does that make sense? |
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|
59:48 | So for example, your uh your anterior pituitary releases chemicals that control |
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|
59:56 | gonads that control your adrenal glands that digestion, they control all sorts of |
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60:01 | at some distance away. It's not signaling, it's using a chemical message |
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60:05 | do. So. Now when that goes, it's going to find a |
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|
60:11 | and there are lots of different types receptors, we have them classed out |
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|
60:15 | . You can see ligand gated G protein couple receptors, catalytic intracellular |
|
|
60:20 | activated. I want to cover these two here right down. Then we'll |
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|
60:24 | the other three in the next All right. But these are just |
|
|
60:29 | of like different structures, how they differently. That's really what it boils |
|
|
60:34 | to. And there's some very generic that every receptor does. And so |
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|
60:39 | you learn the generic thing, then doesn't matter what the receptor is, |
|
|
60:43 | can pretty much figure out how the system is gonna work. And far |
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|
60:47 | often I see students trying to memorize individual type of receptor and what it's |
|
|
60:53 | , right. So let's kind of the big picture stuff. So this |
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|
60:57 | here is the picture from your And you can see what do I |
|
|
61:00 | is I have a receptor ligand It has these molecules and enzymes that |
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|
61:06 | some second messenger that results in the of a downstream protein. Here it's |
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|
61:10 | kind, right? But in what we have is we have recognition |
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|
61:15 | then we have a changing of an signal to an inside signal, that's |
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|
61:21 | , right. I'm changing it from form to the next. And then |
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|
61:24 | inside signal goes and activates some sort effector. An effector is a molecule |
|
|
61:29 | causes an effect. Right. So modulate, we change what's going on |
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|
61:36 | , or we're transmitting that signal and the modulation is, what activity are |
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|
61:40 | doing? Are we turning something on are we turning something off? All |
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|
61:45 | . And then, so that turning or off results in a response in |
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|
61:48 | cell and then you have to turn off because your cells are like your |
|
|
61:53 | and don't waste energy and I'm paying bills and yada, yada yada. |
|
|
61:57 | . So anything you turn on, have to turn off your dad tell |
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|
62:01 | to turn off the the lights when leave the room. OK? Just |
|
|
62:05 | sure because I say that all the . I thought no, no, |
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62:08 | never gonna say that I'm like constantly off the lights, turn off the |
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|
62:12 | , turn off the lights. Let's if you guys can see what I've |
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|
62:17 | described up here in very generic Gotta pull out my pin. All |
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|
62:27 | . So when we're talking about receptor , what we need first is we |
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|
62:30 | a plasma membrane. So I'm going draw a plasma membrane. Look at |
|
|
62:33 | a fantastic artist. I am. you. All right. So what |
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|
62:37 | we need for dealing with receptor What do we need receptor. All |
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|
62:42 | . I'm gonna draw a receptor. receptor is going to be this |
|
|
62:46 | OK. So our acceptor is the giant R, I apologize because I |
|
|
62:50 | to do this without support. So our r it's a receptor. What |
|
|
62:54 | to the receptor? A lien, ? Or a ligand? All |
|
|
62:58 | So we're gonna make the diamond a . Now again, I apologize for |
|
|
63:02 | artwork. All right. So the step is the receptor needs to be |
|
|
63:07 | to recognize the ligand. If you a ligand, that doesn't recognize the |
|
|
63:10 | , nothing's gonna work. That's the step, right? But notice this |
|
|
63:14 | an outside signal. So this is ECF right over here is the IC |
|
|
63:19 | and so that outside signal has to an inside signal. So we need |
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|
63:24 | to convert that outside signal into the signal. And so when the ligo |
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|
63:28 | to the receptor, it changes the of the receptor and the change of |
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|
63:32 | shape of that receptor changes what that is associated with. All right. |
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|
63:36 | that receptor is associated with a OK. So I'm going to make |
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|
63:42 | box for the transducer. So we a transducer and then that transducer does |
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|
63:51 | , right? It's going to activate in that system inside. So it's |
|
|
63:58 | that external signal into that, that , the external into an internal |
|
|
64:02 | Now, not all systems have this step, but I'm going to draw |
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|
64:06 | in here so that you can see . All right. And usually, |
|
|
64:10 | not always what we have is we some sort of enzyme that's associated. |
|
|
64:18 | put it easy for enzyme, some of enzyme associated with the internal side |
|
|
64:22 | the membrane so that the transducer can along and change its activity. |
|
|
64:27 | what we're doing is we're using the to turn on the enzyme, |
|
|
64:33 | And usually what we're going to create a result of that if that exists |
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|
64:37 | some sort of second messenger. All . So that's our second messenger. |
|
|
64:41 | need a new shape in there. think I'll do a triangle. All |
|
|
64:45 | . Now, the second messenger's job to activate the effector. All |
|
|
64:52 | And again, what is the effect we're not concerned about? Um, |
|
|
64:55 | need a new shape here. Uh gonna try to do something weird. |
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|
65:02 | do. That was tough. What we have here is the |
|
|
65:12 | And so this activates the effector and the effector goes on and does something |
|
|
65:18 | change in the cell, right? change in the cell could be something |
|
|
65:26 | turn on something that I turn I can turn on gene expression, |
|
|
65:30 | can change the activation of other right? It's, it could be |
|
|
65:36 | variety of different things. But if see this right, it doesn't matter |
|
|
65:41 | the system is. OK. All the systems signaling systems that we're going |
|
|
65:47 | look at, have something like The one exception being that maybe we |
|
|
65:52 | a system that is missing that internal at which point that transducer is just |
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|
65:57 | the effector. That kind of makes . I can leap over that. |
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|
66:01 | when you look at a, at , at a system and you see |
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|
66:05 | pattern, all you gotta do is oh OK. This is something I |
|
|
66:07 | know. Now, I just maybe have to memorize now the different |
|
|
66:11 | OK? So what I wanna do I want to show you a couple |
|
|
66:14 | these systems and then we'll be done you can go home and you can |
|
|
66:19 | all this information and say, look at all the things I learned |
|
|
66:23 | or didn't. Yeah, I could hear you. Sorry. It is |
|
|
66:35 | activating some sort of factor. Let's that one first. OK? What |
|
|
66:44 | looking at here is we're looking at system like a synapse. OK? |
|
|
66:52 | here we are at the synapse here our message, right? That's our |
|
|
66:57 | . The signal is binding to the . There's not even a transducer in |
|
|
67:01 | system because what that message is doing binding up to a channel and that |
|
|
67:06 | is now opening, this is a gated channel. So when I open |
|
|
67:10 | channel ions flow in or they flow , right, we always draw with |
|
|
67:15 | flowing in stuff, but it could the flowing out and which is going |
|
|
67:19 | cause the cell to either hyperpolarize or depending on which direction the ions are |
|
|
67:25 | , which causes a membrane potential Which means I'm either activating the cell |
|
|
67:30 | deactivating the cell. So far, basic. Everything downstream is more or |
|
|
67:36 | ignored, right? The receptor in case is acting as an effector. |
|
|
67:42 | . That's the easiest my favorite, G protein coupled receptor. Why is |
|
|
67:48 | my favorite? Well, because I in a field that was primarily focused |
|
|
67:53 | this. Plus, there's only 5000 these. So you know, you |
|
|
67:57 | one, you learn them all. . G protein couple receptor, seven |
|
|
68:01 | membrane region. As we mentioned last , it is called G protein couple |
|
|
68:05 | because it is coupled with a G . A G protein is a hetero |
|
|
68:09 | protein, hetero, meaning different kinds meaning three parts. So it's a |
|
|
68:14 | part, different part protein has an , a beta and a gamma |
|
|
68:19 | Now, is that really important? all know it's just something that you |
|
|
68:23 | pick up and you hold on All right, when a ligand binds |
|
|
68:30 | a G protein couple shapes receptor, changes the shape which is interacting here |
|
|
68:35 | the G protein region, right. that causes a change in the G |
|
|
68:39 | the alpha subunit. Basically the alpha job is to bind up to a |
|
|
68:47 | and then has a TPX activity that the cleavage of a TP release |
|
|
68:53 | All right. So what it it says, oh, I'm going |
|
|
68:56 | , and then it holds on to GDP until it's to let go. |
|
|
68:59 | when I bind up to that, when I change the shape of that |
|
|
69:03 | protein, it kicks out the GDP says, bring on the A TPATP |
|
|
69:08 | it and when A TP binds, causes the chimeric protein to separate into |
|
|
69:11 | parts, an alpha subunit bound to and then a beta gamma subunit that |
|
|
69:16 | off and does its own thing and kind of ignores but it has its |
|
|
69:19 | activity, right? We really have now, two transducers, an alpha |
|
|
69:24 | a beta gamma. All right. then the alpha goes off and does |
|
|
69:27 | thing. It, it cleaves that TP. So basically, it's GTP |
|
|
69:32 | . Um our, it's, it's TP activity, basically cleaves, it |
|
|
69:37 | the energy and it comes back and , I'm ready to hang out with |
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69:39 | again, right? And then you can repeat that process over and over |
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69:43 | over again as long as the channel opened up. So this is kind |
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69:47 | what it looks like. All Now, see if you see the |
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69:51 | . All right. So here what have, we have our G protein |
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69:55 | , coupled to the G protein couple . Here's our ligand, it binds |
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69:58 | that. See, we're bound up the GDP, right. We activate |
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70:02 | . See, I'm activating. So kicking out the old GDP. Go |
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70:06 | . I don't like you anymore. in the GTP. All right. |
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70:09 | I'm gonna do is I'm gonna separate and I'm gonna go downstream and I'm |
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70:12 | go, start looking for things that can activate. What am I |
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70:15 | I'm activating some sort of enzyme. enzyme doesn't matter right now. I |
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70:20 | activate this 10, wait, maybe can go activate something else. |
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70:23 | look, that's what beta gamma is . It's activating two different things, |
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70:27 | . And so now I'm kicking off signaling cascade. All right. That's |
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70:33 | particularly helpful because it's pretty generic, it? First one, you guys |
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70:36 | to know signaling through Adal cycles. is the most common type of G |
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70:43 | coupled receptor signaling that exists primarily because nose has all these G protein coupled |
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70:49 | and this is the system that it . All right, we're going to |
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70:53 | more specific. Now, here's our , here's our G protein, here's |
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70:58 | ligand, it binds to it here's the alpha subunit. In this |
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71:02 | case, it's an S subunit. , that doesn't matter. It's activating |
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71:06 | enzyme in the membrane, that enzyme the membrane is called a cycle, |
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71:11 | ? Biologists name things for what they like or for what they do. |
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71:15 | is an enzyme it says so in name, it's a cycle. So |
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71:17 | is it doing? It's taking a cleaving off two of the proteins and |
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71:24 | that last little uh uh phosphate and binding it around and rebinding it to |
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71:29 | ribo sugar to create a molecule called A MP. That cyclic A and |
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71:35 | . So I bent it right back . Really? That's the bent |
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71:40 | All right. And that cyclic A P is now a second messenger. |
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71:44 | can do things. All right. this is the, the second messenger |
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71:49 | moving on. Typically, what admiral does it binds to and activates another |
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71:56 | , an factor called protein KSE This is the most common protein kind |
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72:04 | . You can see in this thing a couple of sub units, get |
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72:06 | cyclic K MP. It, the , when you activate the system, |
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72:10 | happens is, is that it can and activate other things downstream, not |
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72:15 | one thing, many things. So can activate this and it can activate |
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72:20 | and it can activate this over And so you're turning on multiple things |
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72:23 | turning off multiple things in the You can turn on gene transcription or |
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72:29 | off gene transcription through this mechanism. so you can turn a single molecule |
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72:35 | into a massive response inside the cell of the cascade event and how it's |
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72:40 | out to all sorts of different Protein cyclic and P A no |
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72:49 | they all go together. So it's hand in hand. Second, most |
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72:56 | type signaling through phospho dias PDES for . Right here. Once again, |
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73:05 | is light. Look at this. this is how your eyes work. |
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73:08 | going to go in a lot of here a little bit later. But |
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73:10 | essence, same thing. We got G protein. You activate the G |
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73:13 | . What is it doing is an phospho, what do you think phospho |
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73:18 | do? They're looking for Dior to , aren't they phosphor? So that's |
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73:25 | it's doing. It's looking for a bond, cleave it. All |
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73:28 | So that's what it does. It that cyclic GMP which is like cyclic |
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73:33 | MP, right? So it has little cycle cycle and it's gonna |
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73:38 | sorry, that bond right there. it's gonna turn cyclic GMP into |
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73:43 | All right. Now, there's a why it does that. We're not |
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73:46 | to go into it, but it, it, it changes the |
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73:50 | of the cell. So that channels closed because you get rid of the |
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73:53 | that's opening the channels and off it . Does that look any different? |
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73:59 | though there's a lot of different molecules receptor transducer enzyme, second messenger. |
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74:10 | would this be defector? Here's another , phospholipase, man. Another |
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74:20 | Yes, another one. All But notice they're all the same receptor |
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74:25 | transducer enzyme, second messenger, second messenger, Ector. All |
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74:36 | Now, what's going on here? we talked about phospho and no PP |
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74:42 | . I said we're gonna come back it. Well, here we're coming |
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74:45 | to it. And there it this phospholipase looks for PP two and |
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74:50 | cleaves it. So here's pip You can see that right there. |
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74:53 | that head and what it does, cleaves that off and it gives you |
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74:58 | glycerol and it gives you IP three nool trios. IP three is a |
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75:04 | easier, isn't it? And each those molecules are now second messengers. |
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75:09 | , diacylglycerol is second messenger to activate K AC. If I have a |
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75:14 | kine A and a protein kine do I have a protein kine |
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75:17 | Yeah, I do. Ok. right. If I have a fossil |
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75:21 | , what do you think? A , IP three goes and acts as |
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75:28 | second messenger to activate and open So, basically what you can do |
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75:35 | you can flood the cell with All right. Now, why is |
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75:40 | important? Well, calcium also serves a second messenger. It binds to |
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75:44 | molecule called calmodulin. See how clever name is. I'm a modulating |
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75:50 | calcium modulated protein. Ridiculous. How some of these names are. And |
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75:58 | it does is when this gets it acts a lot like protein kine |
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76:01 | does, it turns things on and things off. And so what I'm |
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76:06 | by releasing the calcium is I'm, spreading the wealth. I'm spreading the |
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76:10 | to activate other things and you're sitting looking at me, I can see |
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76:15 | looks on some of your face. have to memorize all this stuff. |
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76:18 | I say you had to memorize No, I said you had to |
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76:21 | the pattern and I'm giving you three of really strong common pathways. All |
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76:29 | got to remember is calmos an It's activated by calcium. I open |
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76:33 | through an effector. What's that It's a channel. How did I |
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76:37 | that? Oh, through a second . It's basically putting all the pieces |
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76:42 | , right? Is my last slide . Yay Raonic acid pathways. |
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76:53 | nothing to memorize on this slide. is just an example. So you |
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76:56 | heard of a Raonic acid when you of a Raonic acid, what do |
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76:59 | think of spiders? Yeah, I too. It has nothing to do |
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77:03 | spiders. All right. But it everything to do with um uh pain |
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77:08 | modulation. It has to do with contractions, all sorts of stuff. |
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77:14 | interferes with the production of these these molecules downstream. They affect this |
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77:21 | right here. Where is it So there's cox and cox too. |
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77:25 | , aspirin gets in the way of things irreversibly blinds it. So the |
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77:29 | doesn't go forward. But why I'm this thing up here is not to |
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77:33 | how and what Aon acid does. want to show you. What are |
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77:36 | doing here? What's that? What's ? Right. What's this transducer? |
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77:48 | this enzyme? So, what does become down here? Well, I |
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77:53 | , really here. What's this right ? That's our second messenger, |
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77:58 | Here's another enzyme, right? What's ? Oh, sorry, there's the |
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78:01 | enzyme, right. What's this acting second messenger? What's that receptor right |
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78:08 | ? An factor. What's calcium doing messenger? Do you see? You |
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78:15 | , you don't have to memorize and every step, you can look at |
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78:19 | like this and you'll see it up over and over. Granted. Right |
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78:23 | , we're looking at G protein couple . When we come back on |
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78:27 | we got three other classes of receptors we're gonna be looking at and I |
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78:31 | you to look at them through that lens. What's the receptor? Is |
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78:36 | a second messenger? Is there a and all this stuff? And you're |
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78:39 | sit there and go. Holy This is so easy. Why do |
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78:41 | make molecular biology hard? You guys a great day. I will see |
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78:46 | |
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