Metabolism | Lipoprotein Metabolism | Chylomicrons, VLDL, IDL, LDL, & HDL

I ninja tears in this video we are gonna talk about lipoprotein metabolism we got a lot of stuff to cover in this video so let's go ahead and get started so when we talk about lipoprotein metabolism we have two different pathways by which we're going to perform this and generally what is this lipoprotein metabolism when we talk about in the two pathways there's what's called an exhaustion his pathway which is the path by which we actually transport cholesterol and triglycerides and different types of lipids to different tissues in the body right exogenous is those cholesterol or those lipid sources are coming from our diet we're ingesting them then there's another pathway we'll talk about right after this one called the endogenous pathway which is those cholesterol the lipids those are being synthesized in our body and we're gonna transport those to different tissues so let's go ahead and get started so first with the exhaustion is pathway we have to zoom in into the actual intestine so we're gonna zoom in into the small intestine right here now let's say here I have some triglyceride let's say I have some cholesterol right and I've just digested that right so now let's say here I have some triglycerides here's my triglycerides and here's going to be my cholesterol there can be many different substances here maybe even some free cholesterol you know cholesterol can exist in two forms cholesterol and cholesterol esters so a lot of our food is rich in cholesterol esters you might have a little bit of free cholesterol now what happens here our stomach pushes the fats into the small intestine once it's pushed into the small intestine if you guys have watched the video on the enteric nervous system we said that we have special receptors located right around the actual you know mucosa and those were called chemo receptors and those chemo receptors could pick up the fat signals right they could pick up the concentration of fats stimulate the submucosa nerve plexus to stimulate special inteiro endocrine cells what type of entire endocrine cells let's pretend here's one of them this entero endocrine cell is called Sisto Kainan cholecystokinin RC ck can go to various different tissues in the body but the main one that we're going to talk about here that we really want to focus on is over here around the liver you know in the liver there's a specialized structure here called the gallbladder so let's pretend here is the gallbladder alright and then from the gallbladder you have something draining it called the cystic duct well the cystic duct can combine with another structure here this other structure is coming from the liver okay you have what's called the common hepatic ducts so right here this is gonna be your cystic duct and this one right here is gonna be the common hepatic duct when the cystic duct and the common hepatic duct fuse they make what's called the common bile duct and then what the common bile duct does is is it comes down here to the intestines around where the pancreas is now the pancreas has what's called the main pancreatic doctor and the main pancreatic duct and the common bile duct fuse and when they fuse they open up into the actual small intestine around what's called the hepatic pancreatic ampulla now why in the world does any of this information important well I told you that cholecystokinin what was his stimulus his stimulus was going to be fat substances fats right cholecystokinin was then released tall tells the gallbladder there's some muscle around the gallbladder right let's say here's some muscle tissue some of this muscle is very very sensitive to the course of the kinda cholecystokinin will then stimulate this smooth muscle to contract when it contracts it expels out certain substances into this actual cystic duct what is that substances these substances are called bile now bile is made up of many different things for example it can have cholesterol in it it can have phospholipids in it it can have water a lot of it is water you can even have electrolytes but the most important components of the bile are two things one is your bilirubin which kind of gives the pigment right to the actual feces and it's a breakdown product from the heme of hemoglobin the other really important one is your bile salts and there's many different types of bile salts for example a couple of the bile salts a couple of these bile salts or bile acids is you're going to have what's called Kolak acid there's another one called deoxy Kolak acid and you can actually combine or conjugate these with other different types of molecules like these guys once these guys get into the intestine they can combine with glycine and make glycocalyx acid or taurine and make Toro Kolak acid but these are the things that I want you guys to get out of this so within bowel there's many different things cholesterol phospholipids water Billy room but the big big big one is these bile salts and just remember why are these bile salts important they are going to perform what's called emulsification of the fat they're going to take a Majan have a big fat globule I'm gonna take that big fat globule and I'm gonna separate it into multiple small little fatty droplets we call them emulsion droplets these bile salts are really important for that imagine here I have a fat here's your fat right well fat is what's called hydrophobic so here's my fat or my lipid here's the lipid and lipids are hydrophobic for example you take oil put it in water what does it do it separates it's like a heterogeneous mixture now that's important because we want in this situation we want the lipids to get dissolved into the actual kind the fluid that because there's enzymes in that so these bio salts they're really really special these bile salts have two different types they have different ends one portion of the bio salt actually is good at interacting with the actual lipids they have hydrophobic portions of them the other part is really good at being able to interact with water so this portion which can interact with the lipid is the hydro phobic portion it's the hydro phobic portion the other portion which can interact with the water is the hydro philic portion and what these guys do what these bio cells do is they bind onto the lipids so now let's come over here let's pretend that this guy right here these triglycerides and the cholesterol this is our lipid substance and what we have here is your stomach actually pushed out into the small intestine right well now it's a big fat globule what I'm gonna do is is I'm gonna take these substances that I made these bile salts coming with the bile right so here I'm going to release out here into the area my bile and remember what is the main component of this bile that we are focusing on here it's the bile salt cyclic acid and deoxycholic acid these biomolecules were then bind with this big fat globule here so what does this molecule right here called this is our fat globule all right fat globule now what we're gonna do is we have these bile salts these blue things hydrophobic portion connecting to the lipid the hydrophilic portion is going to allow for it to interact with water the fluid within the actual intestine why is this important let's pretend here is the fluid right here this sucker just kind of sitting on it like a boat here's the fluid right underneath this there's a special enzyme remember I told you that this black line was representing the pancreatic duct this was the main pancreatic duct we were representing here this guy right here well the pancreas makes some special different types of enzymes one of those enzymes that it secretes is called pancreatic lipase so this enzyme right here that we're gonna secrete is called pancreatic lipase and look at this guy this guy is ready to chew up some lipids alright he's ready to chew up some lipids problem is is he can't get to it it's not dissolved properly so what these actual bile salts do is they emulsify and they separate it they don't break any bonds they're just separating the big globules and now from that look what happens I'm gonna separate this big fat globule and two smaller little droplets and I'm gonna zoom in on one of those droplets now so now let's assume that I rip this big glob into a small fatty droplet here it is okay there's my small fat droplet and this fat droplet contains triplet triglycerides it contains cholesterol in it right this ends on this pancreatic lipase enzyme he sees this and guess what he does he comes over here there's a protein that's actually bound on to this it's right here it's called Co lipase pancreatic lipase comes over binds to the co lipase and then starts chewing some of the triglycerides so from here pancreatic lipase is going to come and do what it's gonna come over here bind with the co lipase and it's gonna start chewing up some of those triglycerides as it chews up the triglycerides what I try glycerides made up of if you look at a triglyceride just a basic general concept here here's our glycerol and then from that you have fatty acids what this enzyme is going to do is it's going to break some of the fatty acids so now we might only have two fatty acids and the glycerol will only be connected to one fatty acid you know what they call these these are called free fatty acids and this right here is called a mono glyceride now after we do this after this pancreatic lipase chews up the actual triglycerides it's gonna spit it on to the two different constituents again what is these constituents let's say right here is going to be my monoglyceride and here is going to be my free fatty acids now again we don't want these guys to start floating up to the top so what should be surrounding these guys again we should have those bile salts those bile salts should actually be surrounding these monoglycerides and these fatty acids and know who else is like hey I want to hop on with you guys - can I join guess who else comes in that cholesterol that cholesterol says hey let me come in here and join with you guys you know who else does I want to come and join with you guys fat soluble vitamins a d E K these are vitamin A vitamin D vitamin E vitamin K they also say hey let me come in here so now we start off with a big fat globule we broke it down into smaller fatty droplets and then after that we chemically broke some of the bonds what kind of bonds here you know kind of bonds are actually holding them together between the glycerol the fatty acids we broke the ester bonds that's the bonds that this pancreatic lipase is actually breaking all right now cholesterol joins vitamin A vitamin A D and K join now here's the here's the thing this is your emulsion droplet that big green guy right there right that we had the bile salts surrounding so we had these bile salts surrounding it like this with the co lipase that was our emulsion droplet once we break down the triglycerides into monoglycerides and fatty acids combined total cholesterol ad E and K it's even more compact more small they now call this compact molecule a me cell they call it a me cell and how much smaller it is than these emulsion droplets about 500 times smaller so this is called a me cell now what happens this me cell starts moving and moving towards the intera site this is going to be an harro site right here so we're zooming in on one massive antara site now because these bile acids they don't really a bio sauce bile acids we don't want them to get taken up we want to keep recycling these guys they get released off so the bio salts get pushed out and then what gets pushed into the cell so now we're gonna have the monoglycerides pushed into the cell and we're also gonna have the fatty acids pushed into the cell now what are we gonna do with these guys now I'm gonna represent them instead of putting that little monoglyceride I'm gonna put em AG mono a seal glycerol right and then I'm gonna put free fatty acids where do these monoglycerides or these free fatty acids go to they go to a special organelle in this cell this organelle is going to be called the smooth endoplasmic reticulum so right here I'm gonna have what's called the smooth ER the endoplasmic reticulum from here they're special enzymes located in this that'll take the free fatty acids in the mono glycerides and fuse them together what are we going to get then from there we'll package that into a spud a special substance which is a triglyceride when we fuse these back together we go back to a triglyceride so now we're gonna have our triglyceride molecule which I'm gonna represent with TG right now we have the TG molecule that we synthesized here the smooth ER will synthesize that another organelle is doing another function this other organelle is going to be called the rough endoplasmic reticulum so the rough ER it's synthesizing a special protein that's going to come over here and combine with this triglyceride what is this protein this protein is actually there's a special protein here which we're gonna make and this protein is going to be called a po protein b48 so we're going to have an April protein b40 here another thing that we're gonna have is we're gonna have a lot of phospholipid surrounding this guy so now combining I'm gonna have triglycerides I'm also gonna package in there some cholesterol a little bit of cholesterol and some cholesterol esters all right so you might see some cholesterol esters you might see some cholesterol some phospholipids I'm gonna package all of these guys into a nice little big size structure here let's represent this with this baby blue color here so now here's this molecule that blue molecule surrounding it we're gonna say that that's a this is actually a part of the phospholipids so the phospholipids inside of this what should we have we should have some triglycerides we should have some cholesterol and even some cholesterol esters but the most prominent component that we should have in here is our triglycerides and then what did we say was associated with it on its surface this protein right here and this protein is called a PO b48 now once we've made this molecule and we've pushed this molecule into this special circulation we push it into the circulation what is that molecule called that molecule right there is called a Kyllo micron it's called a Kyllo micron and this is going to be one of those lipoproteins this is a lipoprotein right here that carries a special special substance called a PO b48 now when this chylomicron gets absorbed across the intestinal wall it's not like normal nutrients like amino acids and glucose and stuff like that they go into the blood this goes into a special lymphatic circulation you know there's a specialized lymphatic capillary located here you know what this guy is called this specialized emphatic capillary located within the intestines is called a Lac teal so it gets absorbed into what's called lacteals these lacteals will eventually combine and make larger lymphatic vessels and then trunks and then eventually there's a big straw sure here it's called the thoracic duct what does this structure we're representing right here this structure is called the thoracic duct the thoracic duct is a big lymphatic structure and what that does is it takes this chylomicron and pushes the chylomicron and some of the other lymph which is the fluid within lymphatic vessels into the blood you know if you know a little bit about your anatomy you have what's called the right subclavian right then you have the internal jugular vein and when they join they make what's called the brachiocephalic vein right here at that junctional point is where this thoracic duct empties its substances into okay so that's where it's empty so now what did we push into the blood successfully we now push into the blood this chylomicron now what is the destination or the function of this chylomicron I'm glad you asked during this while it's moving all right what does that protein add we have to remember all of these proteins I'm sorry guys but you have to able b48 was one of them now there's another little nice molecule he's walking by the chylomicron he's like hey buddy you could use some extra proteins here take these and he throws him some proteins he's very kind of molecule he's very good to us and he should be very thankful for this molecule this molecule is called HDL high density lipoprotein right this HDL is so nice to us and what he does is he donates some of his April proteins to this chylomicron here and again what are some of these substances in the chylomicron I don't want you to forget it we said there's triglycerides lots of them cholesterol cholesterol esters right he donates two really important proteins one is called a PO II which has actually been real scientifically research has shown that it's been related and linked to Alzheimer's disease when there's defects in this and another one which is called a bow see - okay so now these two molecules are gonna become associated with him it's kind of micron so now after this happens after this guy transfers it so kindly and still respectively now look what we have here surrounding this whole big sucker we should now have our chylomicron what the phospholipids it should have inside of it triglycerides cholesterol cholesterol ester and then surrounding it what kind of proteins will have it will have b48 it'll have a PO e and then it'll have c2 ACL so good does right and HDL is really really kind to us because it does other things besides this but now why is this important a PO e is really important for being able to bind on to special LDL or LDL like receptors we'll talk about that later but a plus c2 is really important for activating a special enzyme located in our capillary endothelial so let's assume that we're out of capillary close to our muscles so this is this right here is representing our muscles so what type of muscles the big ones here is gonna be your skeletal muscle so your skeletal muscle and your cardiac muscle these are the two big ones and then over here in orange these cells are representing our Depot sites or a fat tissue so these are some a Depot sites going to the capillaries that serve these tissues there's a special protein molecule you see this green marker right there this molecule is called lipoprotein lipase so it's called lipo protein lipase commonly abbreviated L L I'm sorry LPL actually lipoprotein lipase so it's commonly abbreviated LPL this lipoprotein lipase once this chylomicron comes over here guess what he does and we're gonna represent chylomicron by ch why here right that's our chylomicron he's gonna come over in this a possi to is gonna activate this enzyme so remember a plus c2 activates the lipoprotein lipase what does the lipoprotein lipase do lipase it's going to cut lipids like triglycerides so remember I told you there was lots of triglycerides in this guy tons about out of his composition 85 to 88 percent of it is actually going to be this large amount of triglycerides now once this lipoprotein lipase cuts the triglycerides what's the two components here let's remember this one of the big components that we're gonna release out of this is going to be our free fatty acids that's one component the other component is going to be the glycerol and this is acted upon by the enzyme lipoprotein lipase the free fatty acid is the one that we want to go into the adipocytes and into the skeletal muscle or cardiac muscle so now let's follow this guy the free fatty acids will go into the adipocytes and the free fatty acids will also go into the skeletal muscle what will happen to these bad boys well think about it your skeletal muscle cardiac muscle dude are they gonna want to store it no let's pretend that you're exercising and what I'm gonna do with those free fatty acids if we take these free fatty acids what can I do with them I can break them down by beta-oxidation into acetyl co a then from acetyl co a what can it go through it can go through the krebs cycle from the Krebs cycle where can we take it to the electron transport chain the electron transport chain can then make ATP so for this I can use it for energy what does he think these ad Depot sites are our fat cells are going to use a for they're gonna take those free fatty acids and they're gonna combine it with glycerol not this glycerol because glycerol there's an enzyme that is not present in the Depot sites or skeletal muscle okay and you don't have that enzyme that can actually convert take the glycerol and actually convert it into glycerol 3-phosphate and then combine with the free fatty acids so because of that this you should that glycerol usually comes from glucose and we actually take and convert that glucose into glycerol but these free fatty acids can combine with the glycerol and make triglycerides and realize that triglycerides we can interchange that with another term ta G triacylglycerol it's the same thing okay same way of describing a different way of describing the same thing okay that's that now what happens to this guy he's unloaded a lot of triglycerides so he's pretty only got like a little bit of cholesterol and some cholesterol esters and not really a ton of it so now afterwards what do we have from him well let's see after this reaction let's bring this guy down so now afterwards where is he gonna go remember I told you that it has the a plus c2 which reacts with a lipoprotein lipase once that reaction happens HDL says hey buddy can I have that molecule back so what happens is that a possi to is passed back to the HDL what does it have left now what it remains with if we draw this molecule is we're gonna have again those phospholipids they're what we have inside of it very very little triglycerides very little triglycerides and you're gonna have some cholesterol and some cholesterol esters it's also gonna have that other molecule what was that other molecule called b48 oh was that other one that we said that molecule was called a PO e hey PO e why is this important we said that a PO e is loves has a high affinity for special types of receptors located within the liver and even in the adrenal cortex what is that receptor this receptor is called an LDL receptor so you're gonna call this molecule here in l DL receptor but also not only does a bowi have a high affinity for LDL receptors it also has a high affinity for other types of receptors you know what that other one is called let's do it a different color so we remember it it's called LDL receptor LDL receptor related protein so we're gonna call that L or P it binds on to the LDL receptor or the L RP and then what happens it gets taken inside of the cell once we take this guy inside of the cell what can we do with it we can break down some of the actual proteins now another thing here we have we should mention is that what's the purpose of this b48 the b48 is good at interacting with another type of molecule this molecule is called heparin sulfate which is on these things called pro do they're called proteoglycans so this heparin sulfate is good for binding the b48 and the April II will bind with the LDL receptors or the LDL receptor related proteins take that in now the protein component let's say that in this blue I'm gonna say what happens afterwards is the proteins they can get broken down into amino acids and we can use those for different things the remaining triglycerides we could do something with that too we could take maybe a little bit of remaining triglycerides and we could store that right but here's the big part what about the cholesterol because we didn't really touch the cholesterol the cholesterol is going to go for three general different functions so let's say here we deviate this on to three general functions one function is we can take that cholesterol and we can convert it into what's called bile salts okay so we can take this and actually convert it into components for the bile where we have boom file right which can go and help to emulsify fats what's another function well maybe we don't really need at that point time so we can store it so let's go ahead and store it but the thing is is cholesterol we don't really like to store it in general this form we like to store into what's called a cholesterol ester so there's special enzymes like call it a cat acetyl you have what's called a Co Co a SEL transferees which helps to transfer an acyl group onto cholesterol and convert it into what's called a cholesterol ester and this is just the storage form another thing we could do with this is we could actually incorporate it into the cell membrane so it can actually become a component of the actual cell membrane to help with giving some rigidity to the cell preventing phase transitions and helping with the fluidity of the cell right so that's important now here's another thing we can do with that cholesterol the liver can take this cholesterol along with these triglycerides can repackage them so let's say we take here some of these triglycerides so we take some of these triglycerides we take some of this cholesterol so we branch this cholesterol off over here and then we're going to take and have some proteins that are going to combine with this again okay so we're gonna taken or combine some proteins you know again with inside of these cells you have what's called a rough endoplasmic reticulum the rough endoplasmic reticulum guess what I can do it can make a protein very very similar really the only difference between this protein in this a PO b48 is the way that they're spliced this protein is called a PO b100 okay April be 100 it's literally almost the exact same as April be 48 and they're specially special types of microsomal transfer proteins in here that helped to make it but again the alternative RNA splicing changes a little bit so now we're gonna have to April be 100 we're gonna take some triglycerides some cholesterol and then we're gonna package it so now let's package all of this stuff together when we package all this stuff together we're gonna make another special molecule okay what is this molecule here called this molecule we're gonna make is called VLDL we're gonna make what's called VLDL now let's say that for VLDL i have this pink coating right so as pink coating is gonna represent some of the phospholipids in it and then again what's going to be present inside of it i'm gonna have some cholesterol and i'm gonna have some triglycerides a decent amount of the triglycerides now we said that the triglycerides could come from these chylomicrons where else could they come from remember our body depending upon the bodies you know state let's say that we're in what's called the fed state we could actually synthesize triglycerides so depending upon whatever the situation is that triglycerides not only could just come from whatever is remaining from these chylomicrons but they could come from glucose glucose can actually eventually get converted and Trikke triglycerides as well and not generally but maybe even some amino acids could help to be eventually convert into triglycerides but it's not as common as having high amounts of glucose so let's say that we synthesize these triglycerides now another thing that could actually help with the triglycerides is even glycerol - so having some glycerol you can actually have a lot of glycerol or fatty acids and we can make some actual triglycerides any way we make this molecule we associated with it in a PO be 100 protein and then it gets pushed out into the circulation when this bad boy gets pushed out into the circulation HDL is so kind he's such a giver he's such a giver and what he does is he says hey buddy I noticed that you only have one protein like this chylomicron did and again what is this molecule here called VL DL is r VL deal with chance for very low density lipoprotein he notices hey you don't have very much of these proteins let me give you some so he gives him the same thing he gave to this chylomicron and again what does this guy have him he has some some cholesterol some triglycerides so phospholipids so this guy says let me give you again but I gave this guy so I'm going to go ahead and give you some a po e lipoproteins and I'm gonna give you some a PO C two proteins which are going to be incorporated into this now after he gets this what well this bad boy look like from here it's gonna take these proteins and it's gonna go track to other different tissues what are some of these tissues don't worry we're gonna cover them what does it have around that just so that we're clear here it's gonna have be 100 it's gonna have II and it's gonna have c2 inside of it it's gonna have triglycerides decent amount of it and some cholesterol and some phospholipids and even a little bit of cholesterol esters where does it go again that c2 is like a magnet for these enzymes it's the same enzyme there what is this enzyme this enzyme here is called L P L lipoprotein lipase the a plus c2 is going to stimulate the lipoprotein lipase what is the actual lipoprotein lipase gonna do it's gonna break down the triglycerides when it breaks down these triglycerides what does it break it down into it's gonna break it down into the two components what are these two components one component is called glycerol or do you think that glycerol right there came from we can have it go right there if you go into the liver you know the liver can actually do a lot of different things with this glycerol all right well what's the other big component the free fatty acids now we're in the sweet goodness do these free fatty acids go to these free fatty acids go into the muscle and the adipose tissue and you already know what they're gonna do depending upon the body's demands we could take the free fatty acids convert it into what's called acetyl co a through what's called beta-oxidation take the acetyl co a go through parts of the krebs cycle and then as we go through parts of the krebs cycle what can happen we could go to the electron transport chain and the ultimate goal is to make ATP so that the muscle can contract right but if it's going to the adipose tissue the adipose tissue is more for the storage form so it can take these free fatty acids right and what do we say we said that we can have let's say that this cell also not only takes up free fatty acids but it takes up glucose right so if you have glucose glucose can also get taken up in TD cells glucose can eventually get converted into what's called glycerol and then cliffs are all can go and combine with these free fatty acids and when they do that what do we make we make triglycerides again we're gonna put TG but you can also represent it t AG just to switch it up we'll put t AG okay the same thing so that's the point there now after that happens what do you think is going to occur same thing the HDL was kind enough to give the a plus c2 well this VLDL this VLDL has to be kind enough to give it back so guess what he does after this reaction occurs he gives the a po c2 back to the HDL now afterwards after this reaction has occurred what do we get out of this so after this occurred we get the remaining VLDL all right we get the remaining VLDL now let's do in red because this is gonna be a different molecule I don't want to represent it a little bit differently different colors now in the same way that this chylomicron after it went with the lipoprotein lipase reaction gave that c2 back we call this molecule here the chylomicron remnants have another name for it but just remember after this reaction with a chylomicron react with the lipoprotein lipase it goes back to the liver it's now called Kyllo micron remnant okay and in the same way this molecule right here it's not gonna have a ton of triglycerides not gonna have a lot but it is gonna have some cholesterol and maybe even some cholesterol esters now this molecule right here is called a VL DL remnant but I guess scientist I'd like to give it a different name let's say hey it's that's calling out a VLDL remnant let's call it an ideal an intermediate density lipoprotein and what protein should be associated with it well it gave back the c2 so I gave back to c2 so all it's gonna have now is a po be 100 and a po e okay here's where gets a little tricky and this VLDL remnant or this IDL what is the fate of this guy how is he a little bit different well you know how when I say it as a Bowie it really gains multiple copies of a Polly so it can actually gain multiple copies of a Polly not just one a Polly it might have you know tons when I'm a couple different he believes why am I telling you this a Bowie is really attracted to specific LDL receptors or LDL receptor related proteins l RPS where are those located in the liver and in the adrenal cortex so where could these go pretend that April is like magnets to these guys it can go do the liver back to the liver so let's pretend it goes back to the liver if it goes back to the liver what happens the same thing that happened to the chylomicron remnant happen to this IDL it can get taken up via its a Poe a reliable protein reacting with the LDL receptor or the LDL receptor related protein taken up and get digested into the different components that we did here same thing can happen but another thing where else gotta go he said we said it could also go over here to the adrenal cortex because the adrenal cortex also has LDL receptors let's pretend that here's one here's an L DL receptor or an L LDL receptor related protein we're gonna represent as L R P and it can react here get taken up and that cholesterol could be utilized now if that cholesterol is taken up what could it be utilized for in the adrenal cortex and what can happen here the cholesterol can get taken up into this cells right so here's our cholesterol what could that cholesterol be used for well you know there's different zones here right for example we have the zona glomerulosa then you can have the zona fascicular da and then you can have another one zona reticularis these produce specific types of corticoids for example if you're talking about the zona glomerulosa it makes a special type of molecule called aldosterone if you're talking about the zona fasciculata it makes a special type of steroid hormone called cortisol and if you're talking about the zona reticularis it makes certain types of sex hormones so DHEA dihydrate beyond roster own and another one epi and roster own all right so it can make many different types of hormones steroid hormones or they could just store it in cholesterol esters here's another thing though over here let's say that this um IDL molecule does come back to the liver there's special proteins in the liver let's represent it down here let's say there's a special protein here in the liver let's do it with this baby blue here's this protein it's waiting for these IDL's okay look at this guy he just loves to chew things up this enzyme is called hepatic triglyceride lipase sometimes they write it as H GTL hepatic triglyceride lipase actually should be HT GL hepatic triglyceride lipase now what does this enzyme do its can actually be found in the liver and even a little bit in the adrenal cortex let's pretend that that molecule comes down here so a lot of it actually got taken up via these LDL receptors or LDL receptor related proteins and the liver and the adrenal cortex some of it though can get reacted with this hepatic triglyceride lipase so now what it is this molecule have on it has april-b 100 and even some a PO e what does it have inside of it again it's going to have triglycerides and it's gonna have some cholesterol esters and some cholesterol this a patek triglyceride lipase is going to react with him and what he's going to do is what are you here within the name guys listen to the name lipase so after this reacts here what do you think is gonna come out of this a lot of free fatty acids and a lot of glycerol now this can again go through the many different pathways within a liver or the adrenal cortex right mainly liver though after it does that we drained a lot of triglycerides there this IDL particle comes back out so let's assume that this guy comes back out here right so it comes back out here and guess what it looks like it's gonna be smaller it's gonna be a little bit smaller so now should be a little bit smaller actually it's making a different color to represent the new particle a different particle let's now use Brown here's this new lipoprotein particle and again it's gonna have be 100 it's gonna be a lot smaller and it's only gonna have April Eve for a little bit of time guess who comes back and says hey buddy can I have that stuff back very little triglycerides a lot of cholesterol a lot of cholesterol esters guess who comes back HDL HDL comes over here here's my HDL molecule and he says hey buddy can I have my a pony back I want my a pony back so then this molecule this IDL at this point in time after he gets his triglycerides taken from him he then gives this a pony back to the HDL so now he gives the apoE back to the HDL particle it then becomes a new particle and this particle is the one that people you know get all crazy about and thinks so Negley but it's not it's not very good protein it's not a very good life of protein for us sometimes again this is actually the IDL at this point I'm still now after it gives up to a Bowie all it's gonna have is the a Poe be 100 and again what we'll have inside of it it'll have a lot of cholesterol cholesterol esters and a little bit of triglycerides this is now the bad one this is our bad cholesterol we call this LDL this is our LDL molecule this LDL molecule is actually very interesting so now after let's just make sure that we get this after the VLDL remnant was formed what can happen just well we don't get confused it can go to the adrenal cortex or the liver if the apoE reacts with the actual LDL receptors or LDL receptor related proteins it gets taken into the cell it's done some of it can actually not get taken into the cell and get reacted with a patek triglyceride lipase decreasing some of the triglycerides with inside of that lipoprotein particle and then after that it gives a pony back to HDL and it turns into L do I just want to make sure that we got that now what can this LDL do well here's the thing April I right we said was a magnet for the adrenal cortex and we said it was a magnet also for the liver well now it doesn't have that night in it so he can go to different tissues in the body what are some of these tissues well some of these are actually located within the you know the nads the gonads right so the this would be the male right sex organs the gonads and this would be the female sex organs the LDL these gonads have LDL receptors so they do have some LDL receptors located on the different tissues and what this can do is this LDL particle can go and deliver some of this cholesterol to these don't ads what can they do with these well if it's the female what kind of sex hormones could she make she can make progesterone from that or she could make a sturgeon and if it's the male what would he make he would make testosterone right so it's gonna make testosterone that's what's gonna happen here now that's not just the only place where else could it go it could also come over here remember this LDL receptor this LDL receptor related protein it can also go there so it can say hey I'm gonna go over here drop some more cholesterol off for you so that you can go ahead and make more abbas draw more cortisol more of this dye Hydra at beyond Ostrom more sex hormones but only a small percentage of it actually does this generally it depends upon the amount of a LDL you have and in general most of the LDL most of the LDL tracks back to the liver most of it about how much of it goes back to the liver about 60 to 70 percent of it goes back to the liver okay and the a poby 100 interacts with the LDL receptors and gets taken inside of the cell and gets broken down use that cholesterol for different sources use the triglycerides for different sources now the remaining about 30 to 40 percent so the remaining about 30 to 40 percent gets taken to the peripheral tissues what are some of these tissues don't ads adrenal cortex and one more the macrophages here's the thing LDLs if they stay in the blood long enough they can become very dangerous very dangerous watch this let's pretend that this LDL particle here this is our LDL particle right let us pretend this this LDL particle it's in the blood for a while and it accumulates right here and what's called the sub endothelial spaces right the sobbing Ophelia layer as it accumulates there it can undergo special oxidation reaction so here's our LDL particle here and again what's inside of it cholesterol cholesterol esters and a little bit of triglycerides right with the phospholipid layer around it and only having a PO be 100 it can undergo what's called oxidation you know that's what's called reactive oxygen species these reactive oxygen species can actually oxidize certain proteins on this LDL molecule is's or LDL after it gets oxidized it becomes what's known as after this reaction here with your active oxygen species it becomes oxidative LDL this is dangerous because as this oxidized LDL accumulates and accumulates within these spaces it initiates an inflammatory response which causes these macrophages to come to the area and start actually taking up some of this oxidized LDL how how does it take it up there's special molecules this pink receptor here it's in my hand this right here is called fatty acid translocase also called CD 36 okay fat CD 36 or fatty acid translocase 36 this guy can take up some of these oxidized LDL particles what is this guy right here this molecule this is called our macrophages this is our macrophage but here's the thing after it starts accumulating a lot of these oxidized LDL particles it starts becoming kind of like a a foamy like structure and what is this foamy cells called foam cell so macrophages after they accumulate a lot of this oxidized LDL can turn into what's called foam cells why is this bad because if this happens it eventually this can become so dangerous that it can lead to smooth muscle cell migration into that around the Tunica intima and that actually can lead to the big big danger here which is called a Theo sclerosis right um other situations that can happen I'm not going to talk too much about it but not only can it can react with the active oxygen species but if someone has high blood glucose levels some of that glucose can react with the LDL and it becomes what's called glycated LDLs and that also has been found will put G LDL glycated LDLs they can also be taken up too and then it contribute to the athira sclerotic process now here's the thing we have some other cells here that are so kind us and they protect us from these LDLs and how much they can actually deposit into these macrophages and cause this atherogenic process these beautiful molecules have been so kind to us many times is called the HDL molecule HDL molecules refer to as the high density lipoproteins now this one is weird it actually starts off you know the intestines the intestines can make proteins and so can the liver and these proteins is referred to we're just going to kind of draw like this this protein is called a bow a one it's called a PO a one a PO a one is going to be the initial component of the HDL molecule you know what it does April a1 is so cool it comes over to those macrophages and it sees that it's got a lot of cholesterol in it let's go over and see what it does so cool this guy he comes over here and he sees a lot of cholesterol accumulating here so let's actually show this a boy one over here let's show him though in this orange color so here's this a PO a1 protein all right so a PO a1 a PO a1 what it does is it binds on two special types of scavenger receptors what are some of these scavenger receptors one of the big one is called abca1 you're probably what the heck does that stand for it stands for ATP binding cassette protein and technically a one there's another one called a B cg1 and that's atp-binding cassette protein g1 these a1 molecules first one the first thing that they usually buy that is the abca1 molecules and what this does is is it actually causes cholesterol to get taken up cholesterol to get taken up into these a 1 molecules these HDL molecules these what we call pre HDL molecules kind of like they also call them beta orden nascent HDL molecules right so once we get this taken up into the a1 molecule right it then becomes a little bit more mature right so we're going to take up some of this cholesterol let's represent this cholesterol in green here it's going to start taking up some of this cholesterol into this April a one molecule and it becomes more of what's called a nascent HDL molecule or I'm sorry it becomes a little bit more mature after it becomes a little bit more mature then it can go on and bind to a b c g1 molecules and take up more cholesterol let's represent this as the cholesterol after it starts pulling up more and more cholesterol it's then considered to be a little pretty pretty mature by now alright so generally it starts off as April a1 comes over here binds to the abca1 takes up some cholesterol after it takes up cholesterol they actually call it after it does that they say it's called HDL 3 it can go on to buy it on to other scavenger receptors such as ABC g1 after does that takes up more of this cholesterol it becomes bigger and we call it HDL 2 so generally we start off with the April a 1 all right a PO a 1 and then it goes to HDL 3 then it goes to HDL 2 now we're taking up a lot of cholesterol we're getting all this cholesterol from the actual blood vessel walls where these foam cells are protecting our bodies but you know what else is good at remember these cells over here this these adrenal cortex and the gonads they have special receptors these receptors are called scavenger receptors b1 s RB 1 this brown one here and the Brown ones here guess what this actual HDL molecules can do with this cholesterol they can take this cholesterol that they have accumulated and go over and drop it off to some of these tissues so here let's say that we take this HDL molecule right here and this HCl molecule which is full of cholesterol it can come over here with its April a one protein right it still has that April a one protein here will represent a 1 a 1 a 1 bind on to these s RB 1 receptors and deposit cholesterol into these tissues so that they can make steroid hormones such as aldosterone and cortisol dye Hydra and dosterone if you're going to the female gonads progesterone estrogen if you're going into the male is gonna be testosterone it's so cool what it's got to do something else now once it takes up this cholesterol it takes this cholesterol off right so let's bless but say he's coming over here now he's over here now here's this HDL molecule it has all this cholesterol all nice and good inside of them right it's got all this cholesterol nice inside of them now here's the thing HDL is pretty interesting what does it have on them again it has a PO a one as well as a lot of other proteins like c2 and E and those are good for donating to other different lipoprotein molecules but something else he donates with remember the VLDL he not only donated some of its actual at c2 and E it also gives to this VLDL it gives it cholesterol and then this VLDL gives this HDL molecule some triglycerides but we need a protein to mediate that process what is that protein here call that protein that's mediating this process is called cholesterol ester transport transport protein or transfer protein right not only is this happening between VLDL but it's also happening between the IDL so over here we're still gonna have HDL here's our HDL particle and our HDL particle will have cholesterol and then what is it going to do it's going to deposit cholesterol to the IDL and the IDL is going to pass triglycerides over to the HDL and again this is regulated by the cholesterol ester transfer protein and the same thing happens with the LDL so if we had the LDL over here it's gonna do the same thing here's our LDL here's our HDL molecule right here and again what does it have inside of it it has cholesterol this cholesterol can get passed to the LDL and the LDL can pass some triglycerides and this is mediated by the caresse cholesterol ester transfer protein now the HDL once it gets this cholesterol it normally stores the cholesterol inside of it in the form of what's called cholesterol esters okay what is this molecule that helps to do that so once it takes the cholesterol in these HDL molecules it has another molecule called L cat and all the L cat does is so remember over there the film set was taking the cholesterol out of the foam cells once it takes the cholesterol out of the foam cells so pretend here's the cholesterol CH and we put it inside of the actual HDL particle this L cat is as terrifying that cholesterol into cholesterol esters okay now that HDL what could it do it could just keep going and doing this all right because what happens is it's passing over the cholesterol to these V LDLs ideals LDLs it's taking up cholesterol from the peripheral tissues as donating it to the steroid agenda tissues but in the same way it could come back to the liver at the liver what does it have scavenger receptors s rb1 receptors what can that HDL particle do guys you should already know it should come over here bind on to this with what protein a PO a1 what should have inside of it a lot of this cholesterol that it pulled from the peripheral tissues and then want you to do it should then deposit that cholesterol into the actual liver and then after that it'll decrease in size after it decreases in size it might go back to the original HDL particle like the immature one then go by on to more foam cells turn into an HDL three go by not to more foam cells turn into an HDL two then do what come back and do this again it's constantly happening and it's such a beautiful process now to finish it all off guys I want to give you guys just a general concept here because we talked about a lot of different stuff here but last thing here to finish off is I want to give you guys an idea of the percentages why they call these vldls ideals LDLs hdls so where we talked about chylomicrons that were coming from the exhaustion Espace way these ones generally have the lowest amount of proteins and we're approximating a lot of these percentages okay so in general chylomicrons their protein percentage is only about 1% it's only about 1% the vldls are about 10% protein ideals are about 10% protein but the LDLs they have a little bit more protein component about 20% but the HDL is they have most of the proteins and the proteins weigh the most of the most dense so because of that since it has the most protein composition that's why it's called the high density lipoprotein now triglycerides or ta G remember ta g or T G it's the same thing triglycerides are try a CO glycerol the chylomicrons are carrying most of it okay generally around 88% but let's take that to about 90% to make it easier to remember right vldls these ones are about 55% IDL's are approximately around 30% LDLs are around 15% and so our HDLs okay next part is the cholesterol the free cholesterol free cholesterol is transported in all these guys to not in a high amount but in a decent amount for chylomicrons is about 1% and it's about 10% across the board or VLDL IDL and LDL and it's only about approximately maybe 5% within the HDL okay but the last thing is the cholesterol esters and you can already imagine who was carrying most of it the LDL chylomicrons weren't carrying a lot of it about 3% of it then the VL deals they were carrying some about 15% of the cholesterol esters IBL was carrying a decent amount approximately around 35 around 35% the LDLs were carrying approximately about 50% of the cholesterol esters and then the last one was the HDL carrying approximately about 30% now to finish everything off guys what should be our normal when you're going to get your blood checked getting a leopard profile lipid panel what is the total serum cholesterol so your total serum cholesterol should generally be anywhere you prefer it to be anywhere less than 200 milligrams per deal but that's not good at us know from this you want to know two different things LD HDL and LDL levels HDL the higher it is the better for males it's around forty to fifty milligrams per deal for females it's approximately a little bit more 50 to 60 milligrams per deal if you can get it higher than that the better LDL though this is the bad cholesterol this is the one that you want the lower the better so on average you want this to be less than 100 milligrams per DL it can go up to about a hundred and twenty-nine but that's getting close to borderline but you want it to be ideally around 100 milligrams per kilo any higher and you can get a very very dangerous risk of a thorough Jennison engineers I can't say thank you guys enough if you guys stuck through this whole video with me I thank you guys so much I hope you guys learned a lot I hope it made sense I really truly do and if you guys did like this video please hit that like button comment on the comment section please subscribe also guys you guys get a chance check out our Facebook Instagram and even our patreon account we would truly appreciate it alright engineering as always until next time [Music] you [Music]

Channel: Ninja Nerd

Views: 617,146

Keywords: lipoprotein metabolism, VLDL, IDL, LDL, HDL, metabolism, chylomicrons

Id: wQY0xpwqPfQ

Length: 63min 35sec (3815 seconds)

Published: Sat Jan 06 2018