Endocrinology | Synthesis of Thyroid Hormone

I ninja nerds in this video we're going to talk about the synthesis of thyroid hormone all right so we're talking about the sense of synthesis of thyroid hormone what we're actually doing in this video here is we're actually taking the thyroid gland so you know where the thyroid gland is actually located it's located in the anterior neck just inferior to the larynx or your voice box and it's a butterfly-shaped gland and it consists of these things called thyroid follicles those are the structural and functional unit of the thyroid gland what I'm doing is is I'm taking a thyroid follicle and I'm zooming in on it and taking a very deep look into it okay so imagine this is the thyroid follicle with these things called follicular cells these simple cuboidal epithelial cells I'm going to zoom in on all of these cells and look at the mechanism and the synthesis of thyroid hormone okay all right so first off we're going to go over the steps afterwards we're going to have a quick review in recap of everything we're going to do first thing we're going to start with is where is all of this whole hormone producing action starting with it's starting with the hypothalamus so I like to remember it like this I like to think about HPT axis so hypothalamic right because it's the hypothalamus this is your anterior pituitary right so we're going to put anterior pituitary and then we're zooming in on the thyroid gland right so we're actually looking specifically at the thyroid gland so I like to think about this whole thing we're going to talk about it the hypothalamic pituitary thyroid axis okay so it's going to start about this whole axis there's some neurons or nuclei that's located in the actual hypothalamus and these neurons are secreting the actual a specific chemical that's going to stimulate the anterior pituitary what is those in neurons these neurons that are situated up here they're going to be secreting this chemical called thyrotropin-releasing hormone trh these nuclei are called the para ventricular nucleus okay so the paraventricular nucleus is responsible for actually secreting trh and if you know from the hypothalamic answer your pituitary video that the trh comes down and stimulates these cells here in the anterior pituitary what are those cells they're called these blue cells are called cyril tropes and what happens is the trh actually circulates down through that blood connection that vascular connection which is called the hypophyseal portal system and circulate down and goes into the anterior pituitary stimulates these thyrotropin as a result these thyroid tropes start pumping out a specific type of hormone that we're going to focus on a lot called thyroid stimulating hormone okay so the first hormone that was produced was called thyrotropin-releasing hormone trh the second hormone that was produced is TSH what is TSH do it comes over here to the thyroid gland in these thyroid follicles so now look like TSH does it actually circulates through the blood and it comes over and it binds on to this receptor that's present on the external face of the cell membrane because you know TSH is actually a peptide hormone so it doesn't have receptors inside the cell it has receptors outside the cell when this TSH binds on to this receptor it activates an intracellular pathway it activates specifically AG stimulatory protein that G stimulatory protein is normally bound to GDP which keeps it off but then it's bound to gtp which turns it on so then it's bound to gtp and it becomes active the G stimulatory protein then goes and activates a effector enzyme and that effector enzyme is going to react with the G stimulatory protein and this enzyme is called adenylate cyclase and what does it Dental a cyclase do this G stimulatory protein activates the adenylate cyclase and adenylate cyclase converts ATP into cyclic a MP then cyclic A&P activates a specific enzyme and this enzyme is called protein kinase a here's where it gets good you know there's transcription factors you know transcription factors are specifically proteins that have one component so let's draw a transcription factor here let's say I draw it in red here's the transcription factor here's a little pocket here and here is going to be the part that binds with the DNA protein kinase a comes over and puts phosphates on this transcription factor so look what it does it comes in here and puts phosphates onto this transcription factor when it phosphorylates this transcription factor that transcription factor starts stimulating the genes to make a specific protein so you know whenever there's transcription transcription produces what's called mRNA and then that mRNA will actually go to the ribosomes on the rough ER right and produce proteins those proteins when they're actually made there be a translation those proteins are modified and and changed here and actually have different types of actions that are occurring here in the rough ER then after that they're actually sent to the golgi and they're packaged and modify within the golgi and then what the golgi is going to pack those this protein inside of a vesicle and then these vesicles but you're actually going to mix out of this golgi you're going to pack that actual that protein right there into this vesicle so now I'm going to pack that protein into this vesicle so there's my protein and then what's going to happen is I'm going to take this protein and I'm going to use this vesicle with the cell membrane so now look this vessel clear is going to fuse with the cell membrane because this vesicle is a lipid bilayer this is a lipid by there they can come together and dissolve right so fuse one another when that fuses look what happens after the fusion of that vesicle so now you get this little inward bubble and what are you going to start releasing out here you're going to release out into this luminal space here this protein so then you're going to release out this protein okay so that was the step there that was a step to synthesizing this basic unit of thyroid hormone okay stimulates a receptor activates protein kinase a intracellularly phosphorylate transcription factors stimulates the genes to make a specific protein transcribes it translates it packages it and excretes it out or exocytosed it into the lumen now what we're going to do is we're going to zoom in on this protein we're going to take this protein and zoom in on it what is this protein called this protein is called thyroglobulin Cyro globulin so what did we synthesize essential recension sync we synthesized this flower globulin colloid because it's like a colloid here's where we have the basic unit of our thyroid hormone what do I mean by that you see these I drew circular amino acids I'm going to represent the circular amino acids in this case are going to represent a specific amino acid and this amino acid that I want it to be is called tyrosine if we're talking about tyrosine we could we could show its structure let's say here that structure right here you have an amine amino terminus carbon with a hydrogen and a carboxy terminus and then you got this phenol group coming off of it okay that's the basic structure of tyrosine but we're going to denote it by these circles okay now we have the basic unit here now we need to do some other things so what else do we need for this reaction to occur we actually need iodine okay but where's iodine coming from it's going to come from certain types of nutrient sources now generally here in America we usually put it in the salt right it's like iodized salt but a lot of other food sources but generally it's circulating here in the blood so let's show it here circulating in the bloodstream let's do that in black so let's say here is our iodide but usually iodine in the blood is in an ion form meaning that it has a negative charge so it's not really iodine this is actually called iodide so we have to be specific about this this is iodide now iodide is extremely concentrated in this area so we can say that this is high concentration right so high concentration of iodine over here I can just instead of putting high I can put high like that up arrow and over here there's a very low concentration of iodine so to pump something from areas of low to high requires energy thankfully we have sodium sodium is so good to us look what sodium says he's like hey iodide I got you I'll help you out so what sodium does is he moves you know sodium he's in actually lower concentration inside the cell and then he's actually in high concentration outside the cell so you know what he does he moves from areas of high to low that's a passive transport when you're moving from high to low well guess who else moves with him code transporting iodide so iodide moves with him okay so there's a symporter or code transporter we're removing sodium and iodide it doesn't directly use ATP it's an indirect use of ATP what does it call when there's an indirect use of ATP this right here is called secondary active transport okay so now we got the iodide in here why do we need the iodide okay this iodine is going to come through the cell let's keep following here let's see what it does and look what happens here there's a specific protein here on the membrane let's say here's this protein here and look what this protis protein it might seem like it's not it's insignificant but this protein is very important because we're obviously any mutation it can alter the function of the thyroid hormone production so let's say here in red we draw this protein here okay what is this here protein called this protein is called pen drin it's called pendrick so what does it call it again it's called pin drin and what it does is it pumps the iodide out here into this vicinity okay so now the iodide is going to get pumped out here into this actual luminal space so now look iodized going to get pumped out but here's the next thing that has to happen this is reactive okay because it's got all these charge we want to be able to you know prevent it from having all these problems so that we can put it on this amino acids so look what this enzyme here look at this little sneaky frenchmen enzyme looks like right so look at this guy with the you know the whole a little mustache right this enzyme is a really cool in fun this enzyme is called thyroid peroxidase I'm going to denote this TPL but again I'll write here it's called thyroid peroxidase what this enzyme does is imagine here's his foot imagine here's his foot this guy is going to kick the iodide he's going to kick them and what he's going to do is he's going to kick him so hard that he converts this guy into what's called iodine so you know what you know whenever you go from iodine which is a negative charge to a zero charge that's called oxidation so what is this reactor and this is oxidation oxidation is the loss of electrons he kicked him so hard he knocks electrons off of them okay so look at this enzyme he kicks them so hard knocks electrons off of them what is this step right here called this step is called iodide oxidation okay then he's got this other enzyme he's got he's only got four toes and then look what he does he takes let's say there's a whole bunch of iodine's here he takes these iodine's and he has him on his toes here and look what he does he comes over and he puts onto these little tyrosine amino acids so look we do is you take the iodine's and he puts them onto these tyrosine amino acids so what does he do then let's say that he puts the thing puts an iodine here and an iodine in there and iodine there and iodine there he put four iodine's on these guys this four here is called aya donation so when the thyroid peroxidase puts the iodine on the tyrosine amino acids of the thyroid globulin colloid this is called aya donation okay so it's called io donation all right but then he can do that to other ones too so let's say that he does it also to this guy here so let's say he puts on one there and let's see he puts two on to this one okay you see what he did there this is where it gets really cool now let's apply concept when you're naming things generally you use the term like mono to say one die to say - right so how many amino acids are on that tyrosine - we'll say two we say die but what is die die I Oh doh tyrosine amino acid what about this one same thing it has two of them so die ioad Oh tyrosine amino acid what about this one he has one that's mono so this is mono i odo tyrosine amino acid this one has two so this is die iota tyrosine amino acid look what this guy does he has a hand over here he's so cool that he can actually split his a hand in half look at this he splits it in half he goes over here and splits this guy in half and then he takes his little fingers and he fuses these guys together so then look what he can do he can couple the di T and the di T and couple the MIT and the di T if he couples these guys together he fuses them together what are you going to get let's see if I take a di T a diameter tyrosine and I add it to add i io to tyrosine I'm going to get four iodine's on one of these two tyrosine amino acids we're going to call that T 4 T 4 is another word for thyroxine ok but what if I take an MIT and a di T infuse these together well then I get three iodine's on to tyrosine amino acid so we're going to call that t3 t3 is also called triode oh so i roaning okay sigh rock scene and trial earth are rolling so t3 and t4 collectively are thyroid hormone okay that should make sense now right so iodine oxidation as a nation coupling now there's other enzymes in this area that will try to be able to help in this cutting and re moving these different types of D IPs and MIT s around fiber globulin but in general thyroid peroxidase is helping to be able to kind of put these di T's and mi T's together but there will be other cleavage processes and rearrangements but we've basically in a nutshell have teeth t4 and t3 in our thyroid globulin Cawood but we can't just secrete that out into the blood we have to get these chunks and these chunks out of this so now look guys we have this guy here here's our thyroid globulin with the t4 and t3 in it I'm sorry hormone what we're going to do is we're going to take this whole thyroglobulin colloid with the t4 and t3 and bring it into the cell you see these guys are here these lysosomes they're going to help us to get this thyroid hormone out of the colloid so how did it do this how does it get in you know there's a process where you take substances into the cells called endocytosis so what is this guy going to do he's going to bring so it's going to actually endocytosis whole protein and put it into this vesicle so what is this this reaction right here call whenever you bring this protein substance into the cell and pack it into this vesicle this is going to be called endo cytosis okay now we've brought it into the cell and we have our t4 t3 right there so this is t4 this is t3 but the whole thing is the thyroid globulin colloid right and our t4 t3 are part of that we have to isolate that t4 and t3 out of that so that we only see create that how do we do that these lysosomal enzymes the lysosomes will fuse with this vesicle here so look it fuses with the vesicle and then these enzymes are ready to start cutting things up they're ready what are they going to do they're going to cut all around this fiber globulin colloid and isolate just the t4 in just the t3 so now what are we going to get out of this afterwards all we're going to have left in this vesicle so now what we're going to do is we're going to isolate out of this these two things here the t3 and the t4 so let's say this one on top is the t4 so we'll have four iodine coming off of it okay then over here let's say this is t3 so I'll have three iodine is coming off of it right so we isolated the t4 and t3 out of the thyroid globulin colloid through the action of who are these guys the lysosomal enzymes then we have our functional t3 and t4 now we're going to fuse this vesicle with the cell membrane of the follicular cell when this fuses look what we can do we can release out this t3 and t4 added to the bloodstream but you know t3 and t4 kind of interesting they're kind of to act like steroid hormones so because of that these are actually because of those benzene rings the phenyl rings they're not really good at being water-soluble so we have to transport them in the blood through some type of transport protein so the liver actually synthesizes a specific protein here to transport this actual thyroid hormone through the actual blood what is this protein here called that it actually secretes this protein here is called thyroxine binding globulin okay so this protein right here is called thyroxine binding globulin and what happens is look now I'm going to draw over here I'm just going to bite it in t4 and t3 are transported by this protein called pyroxene binding globulin okay all right so now that we've done that we have almost everything that we need here to make the functional thyroid hormone now we're going to do is we're going to recap everything we're going to finish this video off okay guys so let's recap in an order here so the first thing that had to happen was trh had to be released so trh release from hypothalamus and specifically you could say the paraventricular nucleus trh then stimulates the anterior pituitary so the thyroid ropes but we're just going to put anterior pituitary to release T SH then TSH stimulates the follicular cells right so our thyroid gland so specifically the follicular cells that make up that thyroid follicle to synthesize thyroglobulin so I'm going to put here Cyro globulin so tgb thyroid globulin okay then what the fourth step was is that we had to get that iodide inside so we had to do what's called iodide trapping okay that was the fourth step the fifth step was that we had to oxidize we had to oxidize the iodide right so we have to oxidize the iodine so we'll say oxidation of iodide through the tessai ROI peroxidase enzyme right after it gets transported through the pen during protein into the actual lumen then the sixth step is we have to iodine eight the tyrosine amino acids so ioud in asian of tyrosine amino acids okay seventh step is coupling so then you have to couple so then you have to couple what the deai T's and mi t--'s respectively vit with MIT is T three di t with di T is T 4 then what the eighth step is I have to take that thyroglobulin kalo 23 and T 4 and bring it into the cell so I have to mediate what's called endo cytosis okay of key what dier globulin and with well with the T 3 and the T 4 so in other words we have two endocytosed of the thyroid globulin with T 3 and T 4 in it then lysosomal enzymes lie so zomo enzymes cleave T 3 and T 4 out of thyroglobulin and what is the tenth and final step the tenth and final step is actually going to be the EXO cytosis of t3 and t4 into blood plasma which is bound to the actual thyroxine binding globulin which is then going to be transported to the target tissues all right guys in this video we covered the synthesis of thyroid hormone I hope it made sense I hope you guys enjoyed it in the next video we're going to talk about the effect of thyroid hormone on its target organs

Channel: Ninja Nerd

Views: 307,493

Rating: 4.9611864 out of 5

Keywords: synthesis of thyroid hormone, thyroid, endocrinology

Id: BeI0-xw_cSQ

Length: 24min 21sec (1461 seconds)

Published: Thu May 11 2017