Alright Ningeners, in this video we are going to 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 the two pathways, there's what's called an exogenous pathway, which is the path by which we actually transport cholesterol and triglycerides and different types of lipids to different tissues in the body. 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 exogenous 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 triglycerides, 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 are called chemoreceptors. And those chemoreceptors could pick up the fat signals, right? They could pick up the concentration of fats, stimulate the submucosal nerve plexus, to stimulate special enteroendocrine cells. What type of enteroendocrine cells?
Let's pretend here's one of them. This enteroendocrine cell is called cholecystokinin. Cholecystokinin, or CCK, 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 going to be your cystic duct and this one right here is going to 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 duct. 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 hepatopancreatic ampulla. Now why in the world is 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, 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 cholecystokinin. 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 substance?
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. It 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 colic acid.
There's another one called deoxycolic 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 glycocolic acid, or taurine and make torocolic acid. But these are the things that I want you guys to get out of this. So within bile there's many different things, cholesterol, phospholipids, water, bilirubin, 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, imagine having a big fat globule. I'm going to take that big fat globule, and I'm going to 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 chyme, the fluid, because there's enzymes in that.
So these bio salts, they're really, really special. These bio salts have two different types of, 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 hydrophobic portion.
It's the hydro. Phobic portion the other portion which can interact with the water is the hydro Phyllic portion and what these guys do what these bile cells do is they bind on to 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 push out into the small intestine, right?
Well now it's a big fat globule What I'm going to do is, is I'm going to 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 salts, like colic acid and deoxycholic acid. These biomolecules will then bind with this big fat globule here. So what is this molecule right here called?
This is our fat globule. Alright, fat globule. Now what we're going to 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 is just kind of sitting on 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 going to secrete is called pancreatic lipase. And look at this guy. This guy is ready to chew up some lipids.
All right? 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 going to separate this big fat globule. into smaller little droplets. And I'm going to zoom in on one of those droplets now.
So now let's assume that I rip this big globule into a small fatty droplet. Here it is. Okay?
There's my small fat droplet. And this fat droplet contains triglycerides, it contains cholesterol in it, right? This enzyme, this pancreatic lipase enzyme, he sees this and guess what he does? He comes over here. There's a protein that's actually bound onto this.
It's right here. It's called colipase. Pancreatic lipase comes over, binds to the colipase. and then starts chewing some of the triglycerides. So from here, pancreatic lipase is going to come and do what?
It's going to come over here, bind with the colipase, and it's going to start chewing up some of those triglycerides. As it chews up the triglycerides, what are triglycerides 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 monoglyceride. Now, After we do this, after this pancreatic lipase chews up the actual triglycerides, it's going to spit it out into 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 you know who else is like, hey I want to hop on with you guys too, 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 says 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 what kind of bonds are actually holding them together?
Between the glycerol and the fatty acids, we broke the ester bonds. That's the bonds that this pancreatic lipase is actually breaking. Alright, now cholesterol joins, vitamin A, D, E, and K join.
Now 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 colipase. That was our emulsion droplet.
Once we break down the triglycerides into monoglycerides and fatty acids, combine it with cholesterol, A, D, 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. You know how much smaller it is than these emulsion droplets? About 500 times smaller.
So this is called a me-cell. Now what happens? This micelle starts moving and moving towards the enterocyte. This is going to be an enterocyte right here.
So we're zooming in on one massive enterocyte. Now, because these bile acids, they don't really, bile salts, bile acids, we don't want them to get taken up. We want to keep recycling these guys.
They get released off. So the bile salts get pushed out, and then what gets pushed into the cell? So now we're going to have the monoglycerides pushed into the cell, and we're also going to have the fatty acids pushed into the cell. Now, what are we going to do with these guys?
Now I'm going to represent them. Instead of putting that little monoglyceride, I'm going to put MAG, monoacylglycerol, right? And then I'm going to 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 there's special enzymes located in this that'll take the free fatty acids and the monoglycerides and fuse them together. What are we gonna get then? From there, we'll package that into a special substance, which is a triglyceride.
When we fuse these back together, we go back to a triglyceride. So now we're going to have our triglyceride molecule, which I'm going to 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? Protein is actually, there's a special protein here which we're going to make and this protein is going to be called apoprotein B48. So we're going to have an apoprotein B48 here. Another thing that we're going to have is we're going to have a lot of phospholipids surrounding this guy.
So now, combining, I'm going to have triglycerides. I'm also going to package in there some cholesterol. A little bit of cholesterol and some cholesterol esters. Alright, 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 the 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 do we say was associated with it on its surface? This protein right here and this protein is called ApoB48. Now once we've made this molecule and we've pushed this molecule into this special circulation and we push it into the circulation, what is that molecule called?
That molecule right there is called a chylomicron. It's called a chylomicron. And this is going to be one of those lipoproteins. This is a lipoprotein right here that carries a special, special substance called ApoB48.
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 lymphatic capillary located within the intestines is called a lacteal. 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 structure here. It's called the thoracic duct. What is 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 the 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, right, what is that protein it had? We have to remember all of these proteins.
I'm sorry guys, but you have to. ApoB48 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 them some proteins. He's a very kind molecule.
He's very good to us. And you 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 apoproteins 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 ApoE, which has actually been 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 ApoC2, okay? So now these two molecules are going to become associated with him. This chylomicron.
So now after this happens, after this guy transfers it so kindly and so respectively, now look what we have here surrounding this whole big sucker. We should now have our chylomicron. With the phospholipids, it should have inside of it triglycerides, cholesterol, cholesterol ester, and then surrounding it, what kind of proteins will it have? It'll have B48, it'll have ApoE, and then it'll have C2.
HDL is so good to us, right? And HDL is really, really kind to us because it does other things besides this. But now, why is this important? ApoE.
is really important for being able to bind on to special LDL or LDL-like receptors. We'll talk about that later. But ApoC2 is really important for activating a special enzyme located in our capillary endothelium. So let's assume that we're at a capillary close to our muscles.
So this right here is representing our muscles. So what type of muscles? The big ones here is going to 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 adipocytes, or our fat tissue. So these are some adipocytes. Going to the capillaries that serve these tissues, there's a special protein molecule. You see this green molecule right there? This molecule is called lipoprotein lipase.
So it's called lipo. Protein lipase, commonly abbreviated LL. 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 CHY here, right? That's our chylomicron. He's gonna come over and this APOC2 is gonna activate this enzyme.
So remember, ApoC2 activates the lipoprotein lipase. What does the lipoprotein lipase do? Lipase.
It's going to cut lipids like triglycerides. So you 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 going to 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 and cardiac muscle, are they going to want to store it? No, let's pretend that you're exercising. And what I'm going to 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-CoA. Then from acetyl-CoA, 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 adipocytes or our fat cells are going to use it for?
They're going to take those free fatty acids and they're going to combine it with glycerol. Not this glycerol, because glycerol, there's an enzyme. that is not present in adipocytes 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 usually, that glycerol usually comes from glucose. Um, 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 TAG, triacylglycerol, it's the same thing. Okay, same way of describing, a different way of describing the same thing. Okay, so that's that. Now, what happens to this guy?
He's unloaded a lot of triglycerides, so he's predominantly got like a little bit of cholesterol, 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 going to go?
Remember I told you that it has the ApoC2, which reacts with the lipoprotein lipase. Once that reaction happens, HDL says, hey buddy, can I have that molecule back? So what happens is, that ApoC2 is passed back to the HDL. What does it have left now? What it remains with, if we draw this molecule, is we're going to have again those phospholipids there.
What will we have inside of it? Very, very little triglycerides. Very little triglycerides.
And you're going to have some cholesterol and some cholesterol esters. It's also going to have that other molecule. What was that other molecule called?
B48. But what was that other one that we said? That molecule was called ApoE.
ApoE. Why is this important? We said that ApoE 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 going to call this molecule here an LDL receptor. But also not only does ApoE 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 LRP.
It binds onto the LDL receptor of the LRP 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 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 proteoglycans. So this heparin sulfate is good for binding the B48. And the ApoE 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 going to 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 out into 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, bile, right? Which can go and help to emulsify fats. What's another function? Well, maybe we don't really need it at that point in 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 it into what's called a cholesterol ester.
So there's special enzymes, like called ACAT, acetyl. You have what's called acyl-CoA, acyl transferase, 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 going to take and we're going to 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 it can do?
It can make a protein very, very similar. Really the only difference between this protein and this APOB48 is the way that they're spliced. This protein is called APOB100.
Okay? APOB100. It's literally almost the exact same as APOB48. And there's special types of microsomal transfer proteins in here that help to make it.
But again, The alternative RNA splicing changes a little bit. So now we're going to have the APOB100. We're going to take some triglycerides, some cholesterols, and then we're going to package it.
So now let's package all of this stuff together. When we package all of this stuff together, we're going to make another special molecule. Okay, what is this molecule here called? This molecule we're going to make is called VLDL.
We're going to make what's called VLDL. Now let's say that for VLDL, I have this pink. Coding, right? So this pink coating is going to represent some of the phospholipids in it.
And then again, what's going to be present inside of it? I'm going to have some cholesterol and I'm going to 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 body's, 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 could actually eventually get converted into triglycerides as well. And not generally, but maybe even some amino acids could help to be eventually converted 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 too.
So having some glycerol. You can actually have a lot of glycerol or fatty acids and we can make some actual triglycerides. Anyway, we make this molecule. We associate it with it.
An ApoB100 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. So VL, DL, which stands 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 in him? He has some cholesterol, some triglycerides, some phospholipids. So this guy says, let me give you again what I gave this guy. So I'm going to go ahead and give you some Apo-E lipoproteins, and I'm going to give you some Apo-C2 proteins, which are going to be incorporated into this.
Now, after he gets this, what will this bad boy look like? From here, it's going to take these proteins, and it's going to go track to other different tissues. What are some of these tissues? Don't worry, we're going to cover them. What does it have around it, just so that we're clear here?
It's going to have B100, it's going to have E, and it's going to have C2. Inside of it, it's going to have triglycerides, a 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 LPL, lipoprotein lipase. The ApoC2 is going to stimulate the lipoprotein lipase. What is the actual lipoprotein lipase going to do? It's going to break down the triglycerides. When it breaks down these triglycerides, what does it break it down into?
It's going to break it down into the two components. What are these two components? One component is called glycerol. Where do you think that glycerol right there came from?
We can have it go right there. It could go into the liver. You know the liver can actually do a lot of different things with this glycerol, right? Well, what's the other big component? The free fatty acids.
Now, where 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 going to do. Depending upon the body's demands, we can take the free fatty acids. convert it into what's called acetyl CoA through what's called beta oxidation take the acetyl CoA 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 did 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 into these cells. Glucose can eventually get converted into what's called glycerol. And then glycerol can go and combine with these free fatty acids.
And when they do that, what do we make? We make triglycerides. Again, we're going to put TG, but you can also represent it TAG. Just to switch it up, we'll put TAG.
Okay, but 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 APOC2. Well, this VLDL has to be kind enough to give it back.
So guess what he does after this reaction occurs? He gives the APOC2 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, right?
We get the remaining VLDL, and now let's do red. Because this is going to be a different molecule. I 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 remnant.
So what do you think we're going to call this guy after this reaction? The VLDL remnant. We also have another name for it.
But just remember, remember, After this reaction with a chylomicron react with the lipoprotein lipase, it goes back to the liver. It's now called chylomicron remnant. Okay? And in the same way, this molecule right here, it's not going to have a ton of triglycerides. Not going to have a lot.
But it is going to have some cholesterol and maybe even some cholesterol esters. Now. This molecule right here is called a VLDL remnant. But I guess scientists, they'd like to give it a different name.
Let's say, hey, instead of calling it a VLDL remnant, let's call it an IDL, an intermediate density lipoprotein. And what protein should be associated with it? Well, it gave back the C2. So it gave back the C2.
So all it's going to have now is ApoB100 and ApoE. Okay. Here's where it gets a little tricky.
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 has ApoE, it really gains multiple copies of ApoE.
So it can actually gain multiple copies of ApoE, not just one ApoE, it might have, you know, tons. It might have a couple different ApoEs. Why am I telling you this? ApoE is really attracted to specific LDL receptors or uh, LDL receptor related proteins, LRPs. Where are those located?
In the liver and in the adrenal cortex. So where could these go? Pretend that ApoE is like magnets to these guys. It can go to 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. can happen to this IDL.
It can get taken up via its ApoE lipoprotein 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 could it go we 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 LDL receptor or an LDL receptor related protein. We're going to represent as LRP. 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 the 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 fasciculata, and then you can have another one, zona reticularis. specific types of corticoids. For example, if you're talking about the zone of glomerulosa, it makes a special type of molecule called aldosterone.
If you're talking about the zone of fasciculata, it makes a special type of steroid hormone called cortisol. And if you're talking about the zone of reticularis, it makes certain types of sex hormones. So DHEA, dihydroepiandrosterone, and another one, epiandrosterone. Alright, so it can make many different types of hormones, steroid hormones, or they can just store it in cholesterol esters. Here's another thing though.
Over here, let's say that this 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 IDLs, okay? Look at this guy.
He just loves to chew things up. This enzyme is called hepatic triglyceride lipase. Sometimes they write it as HGTL, hepatic triglyceride lipase. Actually it should be HTGL, hepatic triglyceride lipase.
Now, what does this enzyme do? It 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 receptor-related proteins in the liver and the adrenal cortex. Some of it, though, can get reacted with this hepatic triglyceride lipase.
So now what should this molecule have on it? It has ApoB100 and even some ApoE. What does it have inside of it again?
It's going to have triglycerides and it's going to have some cholesterol, esters and some cholesterol. This hepatic triglyceride lipase is going to react with him. And what he's going to do is, what do you hear within the name guys? Listen to the name, lipase. So after this reacts here, what do you think is going to 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 the 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 going to be smaller. It's going to be a little bit smaller. So now it should be a little bit smaller. Actually, let's make it 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 going to have B100. It's going to be a lot smaller. And it's only going to have ApoE 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 ApoE back? I want my ApoE back.
So then this molecule, this IDL at this point in time, after he gets his triglycerides taken from him, he then gives this ApoE 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 think so negatively about. It's not a very good lipoprotein for us sometimes. Again, this is actually the IDL at this point in time still.
Now, after it gives up the ApoE, all it's going to have is the ApoB100. 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 so 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 hepatic triglyceride lipase, decreasing some of the triglycerides inside of that lipoprotein particle. And then after that it gives ApoE back to HDL and it turns into LDL.
I just want to make sure that we got that. Now, what can this LDL do? Well here's the thing, ApoE 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 magnet, so it 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 gonads. 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 estrogen. And if it's the male, what would he make?
He would make testosterone, right? So it's going to make testosterone. That's what's going to 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 going to go over here. Drop some more cholesterol off for you so that you can go ahead and make more aldosterone, more cortisol, more of this dihydroepiandosterone, more sex hormones.
But only a small percentage of it actually does this. Generally, it depends upon the amount of 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% of it goes back to the liver.
Okay? And the ApoB100 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%. So the remaining about 30 to 40% gets taken to the peripheral tissues.
What are some of these tissues? Go Nads. Adrenal cortex and one more, the macron.
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's pretend that this LDL particle, it's in the blood for a while, and it accumulates right here in what's called the subendothelial spaces, right, the subendothelial layer.
As it accumulates there, It can undergo special oxidation reactions. 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 ApoB100. It can undergo what's called oxidation.
You know there's what's called reactive oxygen species? These reactive oxygen species can actually oxidize certain proteins on this LDL molecule. This is our 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 CD36.
Okay? Fat CD36, 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 foamy-like structure. And what is this foamy cell? It's called a 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 the around the tunica.
Intima and that actually can lead to the big big danger here, which is called atherosclerosis right 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 to and then contribute to the atherosclerotic process. Now, here's the thing. We have some other cells here that are so kind to 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.
It's 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 it like this. This protein is called ApoA1. It's called ApoA1. ApoA1 is going to be the initial component of the HDL molecule.
You know what it does? ApoA1 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 ApoA1 over here. Let's show him though in this orange color. So here's this ApoA1 protein.
Alright so the ApoA1, ApoA1. What it does is it binds onto special types of scavenger receptors. What are some of these scavenger receptors?
One of the big ones is called ABCA1. You're probably like, what the heck does that stand for? It stands for ATP binding cassette protein, and technically A1.
There's another one called ABCG1, and that's ATP binding cassette protein G1. These A1 molecules, first one, the first thing that they usually bind at 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 A1 molecules, these HDL molecules, these what we call pre-HDL molecules, kind of like they also call them beta or 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 ApoA1 molecule. And it becomes more of what's called a nascent HDL molecule. 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 ABCG1 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 mature by now. Alright, so generally it starts off as ApoA1, 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 HDL3. It can go on to bind onto other scavenger receptors such as ABCG1. After it does that and takes up more of this cholesterol, it becomes bigger and we call it HDL2. So generally we start off with the ApoA1, alright, ApoA1, and then it goes to HDL3, then it goes to HDL2.
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 it's good at? Remember these cells over here, these adrenal cortex and the gonads?
They have special receptors. These receptors are called scavenger receptors B1, SRB1. This brown one here and these 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 HDL molecule, which is full of cholesterol, it can come over here with its ApoA1 protein, right?
It still has that ApoA1 protein. Here we'll represent A. 1, A1, A1, bind on to these SRB1 receptors and deposit cholesterol into these tissues so that they can make steroid hormones such as aldosterone, cortisol, dihydroepiandosterone.
If you're going to the female gonads, progesterone, estrogen. If you're going into the male, it's going to be testosterone. It's so cool, but it's got to do something else now. Once it takes up this cholesterol. It takes this cholesterol up, right?
So let's 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 him, right?
It's got all this cholesterol nice inside of him. Now, here's the thing. HDL is pretty interesting.
What does it have on him again? It has ApoA1, 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 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 called? 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 gonna do? It's gonna deposit cholesterol to the IDL and the IDL is gonna 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 going to 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 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 LCAT. And all the LCAT does is, so remember over there in the foam cell, it 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 LCAT is esterifying 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 BLDLs, IDLs, LDLs.
It's taking up cholesterol from the peripheral tissues, it's donating it to the steroidogenic tissues. But in the same way, it could come back to the liver. At the liver, what does it have? Scavenger receptors.
SRB1 receptors. What can that HDL particle do, guys? You should already know.
It should come over here, bind onto this with what protein? Apo A1. What should it have inside of it?
A lot of. This cholesterol that it pulled from the peripheral tissues. And then what should it 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 bind onto more foam cells, turn into an HDL3.
Go bind onto more foam cells, turn into an HDL2. 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, IDLs, LDLs, HDLs. So remember we talked about chylomicrons that were coming from the exogenous pathway. 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, It's only about 1%. It's only about 1%.
The VLDLs are about 10% protein. IDLs are about 10%. 10% protein.
But the LDLs, they have a little bit more protein component, about 20%. But the HDLs, they have most of the proteins. And the proteins weigh the most. They're 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 TAG, remember TAG or TG, it's the same thing. Triglycerides or triacylglycerol. 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%. IDLs are approximately around 30%. LDLs are around 15%, and so are HDLs, okay?
Next part is the cholesterol, the free cholesterol. Free cholesterol is transported in all these guys too. Not in a high amount, but in a decent amount. For chylomicrons it's about 1% and it's about 10% across the board for 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 VLDLs, they were carrying some, about 15% of the cholesterol esters.
IDL 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 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 lipid 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 dl. But that's not good enough to know. From this you want to know two different things. HDL and LDL levels.
HDL, the higher it is, the better. For males, it's around 40 to 50 milligrams per dl. For females, it's approximately a little bit more, 50 to 60 milligrams. per dl 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 129 but that's getting close to borderline but you want it to be ideally around 100 milligrams per deal any higher and you can get very very dangerous risk of atherogenesis ninja nerds 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 down in the comment section, please subscribe.
Also, guys, if you guys get a chance, check out our Facebook, Instagram, and even our Patreon account. We would truly appreciate it. All right, engineers, as always, until next time.