okay i transported distribution the formalism stuff are we clear this don't talk to us on an introduced most fasting little break but I want to do while just start to stumble over his introduction here when we clear with this okay place the ball recorded now let's talk about the hormones into the bloodstream what's happening how they're being the students distributed well they can either be distributed freely just by the one on themselves and you just go to the bloodstream or sometimes it be attached to protein and not be utilizing so it's necessary the good day of lighting is on there that kids going to school some of them can walk to school on the street some of them to ride on buses when they get to this school and it's cold outside who do you think are the first ones that are going to go inside the school to get warms up the ones that are free free walking for the ones that are in a nice warm but the fries welcome months right so the ones this is what I'm saying here has a free hormones are getting used up first the ones on the buses are the ones on a protein will draw on reserve okay thats base with the savior to the free floor Oh [Music] episode up so the zone i have a whole no that's not you're looking at this right that's not what I mention it if I space at night or my fingers and I'm jab it right through here soda how to hold either the difference now right if there is a window in the wall up there would you say that the wall has a hole in it nah profitt a shotgun and flexible there the whole so this is more or less like a window we're not going through the cells that make sense pull this this nice truck now if I extend it is that I'm going to go along here Beyonce don't assume that whole so these are successful little bit what I'm actually drawing over here is the lining you have a field lining of a blood vessel and this is the cheapest any curls so it's like this what I'm showing here but then we're curling it around so that we are making elicit some extent and a blood vessel has Denice tritanus little windows to allow certain things to go through in and out not big they're only on glock 36 so you also have other ones because those those things adults are here or if it's made properly it actually goes through into this layer here now keep in mind that this top you will the obscene what it really looks like a few courses ago drizzled a lot of top of you stick as a phospholipid bilayer this is going to be extracellular fluid this is on the intracellular fluid certain things become thrilled here certain things pants inside so there's water over here and as water here you remember that inside here in eight water this fossil is either lipid here these little sticks for the life of themselves horrible forward side it's awesome right so up here unless the water in here doesn't so we could have certain things go through that membrane things that don't like water sides of lipid compact light through here because it people mix oil and oil together it's a pass right through this mix the water soluble stuff won't be able to do that the Lord is all you'll see it's on our richest training right off because that water not water volved in the water soluble form all when he gets to this area just going to come right back out this isn't like floor so look I'm trying to show you the back to this after the break but what's going to happen here is that lipid soluble hormone can pass right through here if what a soluble stuff want to get in there they have to have another mechanism which I'm going to talk about or that I go through the phoenicia because there is nothing here that's going to prevent water soluble spot to get in systemic them okay and I bet cefaclor is it'll normal is bound to a protein if a child is balance of a fuss the child can still come off it's not here reversible we're going to glue into to the plugs and you can get them all so it's just they're there for a reserve a little side note on this is that if you have kidney disease and protein the protein should not do this if proteins still out in your yard you should not approach things in your yarn but if it was disease it can do that if you lose protein you're also going to lose proteins that have certain hormones on now think about this your dignity you're losing protein you're losing programs are hormones attached to the protein and maybe some little thyroid hormones are taxed there you can see that give it a blues thyroid hormones in the yarn and that person is talking about low levels of t3 t4 so some mess professionals why not put things together they go and got low C 384 we're going to put more that in you and we'll also try and figure out what's going on with your kitty plus if you're going to fix the sideboard ish does that make sense ok that's what you just put things together ok so this is formally and imparting self interaction so again we're doing up dealing with here the tea is the warm up the keyhole is the receptor natural we're jumpin we're suddenly where's the walking feet ok now we have crazy words here lies all that means is anything that binds recess it does that feel horrible anything plus without cronies and a comic alert come forward and we see that you use in your book if you want to use that is going to use the word life that's all it is is just something that attaches to the receptor a hormone is alighting a tea is a life okay and the receptor itself is the binding so I close that lie alright so you put it all together and you're going to have a Zygon binding site when it all together all right just three easy turn freedom okay but it's very specific for instance of growth hormone cannot get into an octuple to me so it has to go Lisa Brooklyn resurfacing sit like a locking key all right this holds into this there's alarm on there's a receptor this is the only one is going to sit like a locking ski very precise yes now the star itself very specific receptors and accession elderly the keyhole so to say and we could have something called up regulations and down really so this is what happens think of yourself inside of themselves okay and you need unique glucose just bear with me I know we didn't talk about influence of the despair with so this is what's going to happen here you need glucose so the thing that's going to allow Zuko's to come inside is a hormone called insulin insulin doesn't come inside of stuff insulin is going to be a key to open up the keyhole to allow the door to open we're inside of the stuff you're inside of itself there's a blood stream I haven't eat employee there's a reception at the keyhole you're starving unique glucose there's tons of glucose out there but it can't get inside and let the influence these opens up the door too loudly close to cummin that's how insulin works we'll talk more about this our team okay but you're inside here and you need glucose so this is a problem you don't know what's going on out there maintenance insulin out there and the insulin doesn't see your acceptance doesn't see the keyhole so what you're going to do is that Meghan I was give you numbers maybe there's only five keyholes out there we searched for insolence what you're going to do is make a bigger net your self is going to make more receptors for influence so firing scepters you're going to make a hundred ancestors hoping that the insulin out there is going to feed now a hundred receptors it's going to be able to see that better does that make sense that's what we call up regulation you're going to upregulate you're going to make more of those exceptions you're going to make that sell more sensitive to low hormone you know maybe they're going a few different insulin others we're going to help you if I putting more receptor is out there to let you can glue onto us does that make sense that's upregulation now all the sugar and all the glucose came in now to sell to the needle like glucose so was it going to do a some signals accepted and it's going to their native proteins are going to come back into the cells break it up and Selena lasted and you're going to do what we call down regularly we got enough glucose we don't need any more influential consumers does that make sense with up regulations down regulation and that are so much power that space is what what is control of this negative feedback to control how much of this influence or the Cornwall per se is going to be sensitive or not sensitive okay so it's really responsible to sell itself what's happening inside okay where we're at alright so let's talk about these receptors of formal okay now receptors for catecholamine mm that's a fancy word for a group of chemicals good examples of this is epinephrine in your internet epinephrine and norepinephrine are a group of things both catecholamines that you're going to see quite often okay so catecholamines and peptide hormones these are either small hormones or more soluble subject they're either large hormones or their water receptors of water soluble one they can't get into the stuff category okay they are kind of like this that's a catecholamine like norepinephrine epinephrine or certified one this cannot get into tears of water soluble right and just explained in the flip side of that right through here water soluble it can or if it's a big one it just can't be completely here so in the commons it will just bring say right off of here so these receptors are connected and have to attach itself to something that's on the outsides itself it's going to be a receptor that's made in the cell membranes that make sense so it successor is going to be on the membrane and stuff this is going to win his affections is to kind of changes say dozens of brigade things that we'll talk about and then it tells us by the someone to do right ecs exercise influence ICS intracellular inside themselves is that clear water or large monsters catecholamines are just specifically epinephrine Arthur number but catecholamines and peptide hormone kind of works similarly in where the receptor is okay they can be like I said they can either be water soluble or they could be large enough either way they seem pass through here so we better happy outside himself alright then we had a thyroid and steroid hormone these are lipid soluble formal or very small forms these are one that can pass right through here to look for its acceptance its receptor is going to be something in the cytoplasm or keep in mind that there's a nucleus here and then in police itself as a nuclear envelope and that nuclear envelope is the same thing as the phospholipid bilayer that has two of those layers so worth the same way if there is something to pass through here look for its receptor is not in a cytoplasm it can easily pass through the nucleus soon and look for these doctors inside the nucleus does that make sense did it color coding the water-soluble hormones and large hormones its receptor will be someplace outside the membrane or on the cell membrane and stuff batter wizard soluble hormone or smaller hormones in squeeze right through here look for a successor getting to the cytoplasm and it's not clear compact through the nuclear membrane and financial structure inside the nucleus exactly r SS this is my art therapy all right I suppose me just verbalize something all right they work similarly on that now classes the receptor reiterating on this the membrane-bound receptors is here in red they're going to be integral proteins proteins that are going to be gone through the whole membrane itself with the part of the membrane these are four hormones that cannot enter the cell the interactive logins are worse soluble or large this involves will we call a second messenger system I'm going to get in quite a hardest part of the whole when this business before the quantity first was a first messages we don't call the first messenger but that message has got to get something through sighs hear the message not to form on the message so it's got to get the message into here so there's going to be a fur gain of stuff that goes on to get that message in sergeant stuff this attachment here it kind of changes gergana things happen here and then a treasured messenger that just got it is going to be in here we'll go through that I got a little video to show you okay it's a chain reaction that happens and the law gives our word soluble or larger like protein hormones polypeptides word on catecholamines the things that cannot get through that FilmOn just like that the question is are possible by later and there is a members of membrane-bound stuff then we have accepted that are found intra still early right inside the stuff degree these are in the cytoplasm ordinate with these are the one owns it can pass through that popular supplies they're the ones that we're talking about the steroid hormones hormones like testosterone estrogen progesterone 12 n was own only it's real cortex one also are going to do that cortisol aldosterone and the thyroid 11 by shows before has he 384 and they could pass right through that possibly by layer finest receptors someplace inside now let's focus on the members membrane great meta grain boundary surface these are the most difficult and challenging for students and for myself to teach so I would explain that then we go for the hardest and work their way down the easiest for us explain we have two ways that the red we're just on the red now about the green we're just talking about the membrane-bound of recession is over here we can either do a tacit event that involves something cold and g protein or one where it doesn't involve a g-protein and tell the second messengers someplace inside themselves what to do so let's talk about the g protein first now it's the most advanced this is the most complex 1 i'm a few different ways of teaching it i'm going to verbalize it here firstly i'm going to show you a picture i'm going to give you an analogy with a nightclub and then i'm going to show you a little short video for about a minute minute assume i'm hoping that one of those are going to click ok so there's a lot of words in here in skinless chemicals and stuff ok so if you watch it is a good time put the titles down and just live it it one of these will flip if you want to write stuff that's fine though I got in trouble one keyboard I just my teacher says I can't write to us I'm recommending you not the writing thing everything is recorded everything is on the tower ok all right let me fertilize this first and i'll give you my little scenario now so what's going to happen here is this cascade has been to give an example that we're going to increase something called camp with the cyclic adenosine mom's process that's what that's what the messages in here we got to precision particular one on Tinian examples so this is what's going to happen our hormone is our first messenger we never refer to as the first messenger but we do refer to something else the special messenger you need understand what is the first met well the hormone needs to get its message into the cell but it can't get into the self physically so how to go lucky well first the hormone is going to attach itself to the memory okay then what's what happen is it's going to bind to this g protein which is located in the membrane itself of procurement first with the g protein the d protein is going to be activated they don't claim this the g protein has something on it called gdp want to die phosphates and what a good activated there's a GT pieces inside the cell that not salted DDPs dtp is watching pride boxing has three boxes so if the g protein gets activated the gdp gets knocked off by GT see that now attaches to the g protein and now as its activated g protein it's going to have another ends on the insider membrane called hi Dennis identity slightly is it ends with AFC it's at any time that gets activated once it gets activated it's going to produce something called Camp cyclic adenosine monophosphate this is the second messenger the message you need to get inside itself how it knows to be activated from outside themselves telling going through all these steps cast them by the protein kind of yet another enzyme and with asp protein kinase called the phosphorylation on certain procedures this means ATP to occur between energy it needs energy for that to happen it says I want to activate protein of whatever that formal was supposed to tell to do and I'll explain what this is in a moment so let me just explain to you what this is all about living in analogy of the nightclub so i've been using for a number of years and things can work out let's say I want to go to New York City and there's tons and I closed down what I want to go to some little catacombs ok now I'm the hormone and I want to go in to see the show at the nightclub so I'm going all over New York City and there's tons of receptors there's tons of nightclubs I need to go through specific one locking feet oh my go to catacombs I finally find it so I said this is it I made it attacks on us right here but I can't get inside ok now the reason why I cannot get inside since is the big guy that's right in front there he's got a big G on it on a shirt that's not for tomorrow and for g protein ok so i can't get inside now the other thing about this analogy is that even on the hormone I'm not I not need I'm not supposed to go inside that's the only I got to try and figure out what I went to renounce what's the message that I want you to show ok but I can't get in because it's a big g protein but the bouncers there the big G so he's got a i'm saying i want to get in so he's gotta change say he's got to get activated by turning around and opening the sword you said I'm saying so he's gotta change safe to do that he opens the door and inside there's a Maitre D' there he's got a call to maitre d so I generally cyclades is the calling you gotta call the maitre d the maitre d is there and it just happens in this make sure these names have to be tamped go figure so his names their camp now he's the second messenger I want to get a good seat he's going to take me to a good seat but I got a huge something before what do I have to give him that I get us a seat right see I got a Duke him right I gotta give them like a twenty twenty bucks so it's close to me to do that ATP it's costing me energies close to me Felton so I give him a 20 bucks and then he takes me to a great seat and I see the show that's the that's the whole thing I wanted to be able to see the show Gold does that make sense let me now let me show you a picture and i'll say how the rapidly thing in a moment but this is the picture and look what's happening here here's a horrible yellow it can't get in the side so what is ill it binds to the receptor this is going to change the one case here's your team proteins when this page is shaped this activates the g protein so that tcp cannot gdp comes off now ETP is attached to this and this is now going activate this end on a generally cycling when this gets activated utilizes ATP it's going to produce a lot of camp cyclic adenosine monophosphate once it comes pouring out of here it's going to activate protein kinase and do whatever it needs to do so this hormone is wanting to do the jail thing here but have to go through all these steps to get that message across is that clear let me say this video epinephrine is one of many hormones that is water-soluble hydrophilic and therefore unable to cross the hydrophobic plasma membranes of its target cells instead it binds to receptor proteins located in the plasma membrane and does not enter the cell when epinephrine binds to beta adrenergic receptors on the liver cell G proteins on the inner side of the cell membrane are activated each g-protein is composed of three subunits and the binding of epinephrine to its receptor protein causes one of the g protein subunits to dissociate from the other two the g protein subunit which dissociates from the author's carries a gdp which is replaced by GTP when the subunit is activated the activated g protein subunit then diffuses within the plasma membrane until it encounters adenylyl cyclase a membrane enzyme that is inactive until it interacts with the g protein subunit when activated by the g protein subunit adenylyl cyclase catalyzes the formation of cmp from ATP the cmp formed at the inner surface of the membrane diffuses within the cytoplasm where it binds to and activates protein kinase a an enzyme that adds phosphate groups to specific cellular proteins in liver cells protein kinase a phosphorylates and thereby activates another enzyme called phosphorylase which converts glycogen into glucose 6-phosphate the glucose 6-phosphate is then converted to glucose through this multi-step mechanism epinephrine causes the liver to secrete glucose into the blood during the fight or flight reaction maybe said that brought I'll be honest II that's probably the hardest part of all endocrinology freedom not saying anything else is easy I'm just saying everything else is like there's a lot of mornings overwhelmed by the volume but this is very conceptual and I think that's probably the hardest thing improve speed actually understand all right questions about that no all right this is just showing the same thing another pictures and words over here to fall number is the same thing yeah now let me go back to this prosthetic this part here where psychotic skipped over this particular status and this part here y is for hormones that are water soluble in large size epinephrine and norepinephrine they happen to go very fast over when a full even though the long cascade that is very fast the reason why is because you guys visualize that this receptor is bound to getting free to mention there is a g-protein here there's one over here is one of the process one in the stomach sense they're abducting three dimensions so what's happening here here there is a receptor it can activate three different g proteins or more because it's an example and each one knows to do see how it is compounded so even though one more month over here the process that happen so rapidly because it could activate many things at the same time is that clear the hormones that are epinephrine norepinephrine they're responsive very quick even those if they cascade of events test our own have quick because of this amplification and a physicist a fatal dip ok alright other second messengers I'm just gave you an example of camp but there's a lot of other second messengers that fuels are saying now i am not going to hold you in this course on the sandals other mechanism this is freaky tail and it's a lot there is enough to keep you busy you need to understand camp and the way this works is because that's how pharmacology works we can actually walk g proteins or we can accelerate steep and that's how certain medication when you get into want ecology you'll be learning about the g protein again or at least just review but that's where it's going to come up again that's why I gotta teach us to know most of them take some sort of pharmacology in your future classes okay even for radiology because you got to learn about radial stare right in that way misty so these are other second msgs not going to hold heaters know those mechanisms however I do want you to know the other names is it I can take you right to mouth so i might say all the following and second messengers except you should know what they are okay so understand this camps mechanisms as i show you to just you know what all these different scenarios but don't worry about the mechanisms of the second messengers just know what ones they are okay if you're really inclined to know a little bit more than you can look at the other diagrams that I have up here but I'm not going to hold you to remember them just show me what's going on here it looks pretty much the same there's a reset relations d protein but instead of making ham come out so that is of the Kolkata t3 assessment it's the same way as using my analogy we go to and I wanna go to that nightclub why go to catacombs the g protein is bouncing it still at the same place I max but this night when he opens up the door to maitre d's not there but in this case it might be my brother who owns the place he's the owner so now he is the second messenger so everything up to that point is still the same but now it's my brother and in this case he's going to take me a different way to get a good seat maybe you'll pick me up on the balcony but I'll have to do come he's my brother I'll slap him silly i'll tell my mom alright so it's just different mechanisms that on maybe another dad's old and it's the manager and the mac soul your your John's brother don't worry about is I'm going to take you down using down in stellar to get up to that spot over there jump into things does that make sense so up until that point it's going to be the same but the second messengers are different okay another story another one of the second messenger exploding I see three let's do that okay all right and this is more detail to learn a little bit more about g protein is the alpha human subunits and beta subunit so much detail about that so this is a listen like you feel should you need to go there now these are the hormones that do what I just showed you don't have to memorize them a link putting this up here to be complete these are all the war models that use the g protein for yourself to code establish ones are there in this essence to gold catecholamines epinephrine norepinephrine vol test five or peptide or protein normal we're excited ok or large monsters and these are the second messengers list again you don't have to worry about the mechanisms ok now we're going to get a little simpler now the hormones that is water-soluble cannot go through here so if we stuck there's something someplace on the membrane there to be a g-protein here in a whole thing I just explained 24 in certain hormones they attach 20 subjects that doesn't have a g-protein here I think there isn't a bouncer to the nightclub that you could just walk in and see the second messenger right there does that make sense so pretty much the same we just don't have a sound if you just so happen to eat proteins and certain hormones to exactly so let's just simply be close the g proteins not included okay and it's pretty much space to the same type of thing okay and it's also very rapid because the whole cascade away I crunching push this button and it kind of tells other things wouldn't do so it's basically this there's no key protein so I have a g-protein beam that connection between identity generally side plates and the receptor this is attached to this will now swaddling cycling and there's no t protein we're just getting the balance does that make sense syphilis okay and these are the war long let's do that with insulin included on this all right yeah I will ask you about it really just being complete there's just too much of those one you list me to know this biochemistry system of war that subsection to haunt you but just pretty serious be complete if you know that's catecholamines and the protein or peptide hormones to put okay questions about that all right now let us talk about the opposite now or the other one we're done with the red here like immunity protein what without a deeper now let's talk about the lipid soluble for the small formal that can pass through here and look for it to be stuck there either in the cytoplasm it's not very fast easy Ziggler envelope and looks like a circus even useless it's linking them more simple I'm now going to read this all to you and I'm going to show you the picture let me more anxious here's the cell membrane phospholipid bilayers that's this okay here's all the side applause here's the nucleus and here is particular edibles keep in mind nuclear envelope is the same architecture as its cell membrane you want to get it to phospholipid bilayers there you need to protect yourself inside your who is better than just inside themselves some extent but if you can pass through here at the pass through here is possible is pilot what's going to happen is this this stairway normal can easily pass through the cell membrane look for if you suck in the cytoplasm it defines its super if it doesn't it's kind of old further and go inside the nucleus it looks for in receptor this receptor is actually called chaperone protein okay several novels once this by one and several molecules discusses inactivated come walk and now you've got receptor hormone complex then by some place on the DNA at certain protein it goes through transcription to make me mrna that goes outside here's Austin translate these needs all the transcription translation you understand it it's to make a protein and that makes encloses so that message is done celta makes it it has to go through this okay my ex about transcription steroid hormones are not water-soluble they travel in the blood attached to protein carriers when steroid hormones arrive at their target cells they dissociate from their protein carriers and pass through the plasma membrane of the cell some steroid hormones bind to specific receptor proteins in the cytoplasm and then move as a hormone receptor complex into the nucleus other steroids travel directly into the nucleus before encountering their receptor proteins not shown the hormone receptor protein activated by binding to the hormone is now able to bind to specific regions of the DNA these DNA regions are known as the hormone response elements the binding of the hormone receptor complex has a direct effect on the level of transcription at the site messenger RNA mRNA is produced which then codes for the synthesis of specific proteins but because this steroid hormone has to appear look for stuff up there look over here and hold a little comes here there is an amplification either it just shows how to do one receptor that complex goes on here it doesn't get amplified so hormones that utilize this steroid hormones and ac3 mp4 happens to be making its products once slower so what I shows you in red over here that make sense this is just a handful price alright so adult amplification that's going to fit so that's why it happened to slow down do it and these are the ones that do this sex steroids which I mentioned a few on their disposal progesterone texted all the ones that come from the exam cortex which we're going to find out soon enough aldosterone supported on and androgens which are basically sexier way and the thyroid hormones so those are the ones that do that okay