Transcription
Welcome back to Dirty Medicine's Dirty Biochemistry series. This video is on part 2 of lipid transport.
As a brief summary, in part 1 of lipid transport, we talked about how dietary lipids move throughout the body, initially passing through salivary lipase, then going through the liver where bile salts get thrown at them, and ultimately surviving pancreatic lipase, which is a very potent way of destroying fats. Ultimately, we form chylomicrons, which enter enterocytes in the small intestine. That's where we left off.
So, with part 2 of lipid transport, we're going to pick right back up with the chylomicron at the intestine. So the chylomicron reaches the intestine, and then it needs to go somewhere next. Next, from the intestine, the chylomicron, depicted here in purple, will enter the lymphatic system.
Okay, so it's in the lymph now. The lymph is depicted on this slide as this sort of rectangular black area. So the chylomicron has made it to the lymph now. In the lymph, the chylomicron will have its first apolipoprotein receptor act on it, and that's depicted here with an orange triangle. This is ApoB-48.
Now, as you'll see in this video and in part 3 of lipid transport, there's a certain theme when it comes to lipid transport, and that is that there are what is referred to as apolipoproteins that act on various players in this biochemical pathway. Now, if you're overwhelmed by the different ways that these apolipoproteins are written, for example, ApoB-48, ApoC-II, ApoE, etc., etc., don't worry, because for each of the apolipoproteins, I have an awesome mnemonic to help you memorize what they do and what their role is in this pathway.
But anyway, this is the first time in the pathway of lipid transport where you see an apolipoprotein come into play. So the way that you're going to remember what the ApoB-48 apolipoprotein does is B-48 should make you think of the B-48 bomber, a famous aircraft, the B-48 bomber. Now, instead of this airplane dropping bombs, I want you to imagine that it drops chylomicrons, or "chylo-mike bombs," if you will. So instead of regular bombs, the B-48 bomber is going to drop chylomicrons from the intestine or from the GI system into the lymphatic system. And that's just the role that ApoB-48 plays. It mediates the release and the secretion of chylomicrons from the intestine, right from the GI system, into the lymphatic system, because it's very important that chylomicrons are formed and ultimately go downstream where they're supposed to end up. So if on test day you have a question about what ApoB-48's role in biochemistry is, you need to think: the B-48 bomber dropping bombs, or dropping the chylomicron bomb on the lymphatic system. So that is the role of ApoB-48.
So here's where we are. The chylomicrons were formed in the intestines, and then ApoB-48 mediated their release from the GI system into the lymphatic system. And now the chylomicrons have made it into the lymph. Now, where do they go after the lymph? Well, the next place that they're going to go is into the systemic circulation. So now they're in the blood.
So shown here in the second sort of rectangular black line is the chylomicron in the systemic circulation. It still has the ApoB-48 apolipoprotein on it, but it's about to get some more apolipoproteins as well. So many of you probably have heard that there's the "bad cholesterol," which is LDL, and there's the "good cholesterol," which is HDL. And the only difference is the density, right? HDL is high-density lipoprotein, whereas LDL is low-density lipoprotein. So don't worry about it for the purposes of USMLE and Comlex, but just know that the density is really what's different between HDL and LDL.
So many of you already know that HDL is the good cholesterol, but have you ever thought for a second why? Right? Why is HDL the good cholesterol? Well, one of the roles of HDL is to put more apolipoproteins on a chylomicron, and those apolipoproteins will have downstream effects that are important for correctly processing fats and cholesterol. So along comes HDL in this pathway. HDL is sort of a carrier molecule. It has two apolipoproteins that it's basically shuttling around this system. It's going to show up here, and it's also going to show up again later on.
Now, when it reaches the systemic circulation where the chylomicron is just chilling, enjoying life with its little ApoB-48 hat, it's going to donate HDL, that is, it's going to donate ApoC-II and ApoE to the chylomicrons shown here. So the chylomicron is still in the systemic circulation. It's just going to kind of move a little bit to the right. And when it's moving through the systemic circulation, the high-density lipoprotein is going to donate ApoC-II and ApoE.
Now, when this happens, the chylomicron now has three, right, three different apolipoproteins sitting on its shell, if you will. It's got ApoB-48, shown here in orange. It's got ApoE, shown here in that sort of mustard mucus color. And it's got ApoC-II, shown here in that sort of maroonish color.
Okay, so here's where we are. Our purple chylomicron has three apolipoproteins on it. It's got ApoB-48, which came from the GI system and sort of helped the chylomicron reach the lymphatic system. And then it was donated ApoE and ApoC-II from HDL, also known as the good cholesterol. So if I can sort of just crop out the chylomicron from this picture and stick it in the middle of the slide, here's where we are so far.
Now, we already talked about the mnemonic for what ApoB-48 does. Remember that B-48 should remind you of the famous aircraft, the B-48 bomber, which drops the chylomicron bomb on the lymphatic system. But I need to talk to you first about what ApoC-II does, as well as ApoE. And then, after I go over the normal pathophysiology, I will tell you exactly how you're going to remember this with an awesome Dirty Medicine mnemonic.
Okay, so ApoC-II is going to activate what's known as lipoprotein lipase, which is commonly referred to in biochemistry as LPL. So ApoC-II mediates the activation of LPL. Now, what LPL does is it actually hydrolyzes the conversion of triglycerides into fatty acids. So ApoC-II on this chylomicron activates LPL, and then LPL will hydrolyze and cut those triglycerides into fatty acids for absorption.
So, how do you remember what ApoC-II does? Well, I think about C-II, right? The two C's. So ApoC-II cuts and cleaves. ApoC-II, the two C's, ApoC-II cuts and cleaves. Okay, not only does it rhyme, but it makes sense. C-II, which means to seize, to seize, cuts, and cleaves. Okay? So ApoC-II cuts and cleaves the triglycerides into the fatty acids by activating lipoprotein lipase.
Now, something that's incredibly high-yield that you should absolutely know at this point in the biochemistry is that lipoprotein lipase, in addition to being activated by ApoC-II, is also activated by insulin. So if you think about this, insulin activates LPL, lipoprotein lipase, and that cuts the triglycerides into fatty acids to be absorbed into the body.
Now, if you have any clinical exposure so far, I want you to imagine in your head what a really uncontrolled diabetic looks like. And I'm talking about someone whose blood sugars are so high that they're always in diabetic ketoacidosis. These people are oftentimes really, really frail, right? They're really thin. And often, when someone is diagnosed with type 1 diabetes early in their life, in that first week where their blood sugar is in the six or seven hundreds, they're losing a ton of weight. And that makes sense, right? Because if insulin activates LPL and cuts triglycerides to fatty acids so that fatty acids can be absorbed, if you're diabetic, which is to say you don't have insulin, then you can't store those fatty acids in your body. So you lose weight very rapidly. So that's why early on in the diagnosis of type 1 diabetes, you're not going to have weight gain, you're going to have an incredible amount of weight loss.
So now we've got two awesome mnemonics that tell us what two apolipoproteins do. ApoB-48, the B-48 bomber that drops the chylomicron bomb. So again, ApoB-48 mediates the secretion of the chylomicrons from the intestine/GI tract into the lymphatic system. ApoC-II turns on lipoprotein lipase, which hydrolyzes and cuts triglycerides into fatty acids to be absorbed by the body. So ApoC-II, to seize, cuts, and cleaves.
Now let's talk about ApoE. So the other piece, the other apolipoprotein that came from HDL was ApoE. Now, ApoE has an incredibly important role in this system that cannot be understated. I'm going to simplify what I'm about to say to the best of my ability, but this is a very complex topic in terms of how ApoE works in this pathway. So far, we've talked about chylomicrons, but ultimately, what happens is that chylomicrons and all of the other cholesterol pieces here, which are known as LDL, VLDL, IDL, these are all different ways of depicting cholesterol. But all of those parts, all of the things that end in DL and chylomicrons, ultimately have to be broken down into what is referred to as remnants.
Now, these remnants, which can be chylomicron remnants, VLDL, IDL, LDL, all of the stuff, everything that in your brain you associate with lipid transport, has to be broken down into remnants so that the system can recycle it. Now, ApoE is the receptor that does that recycling. So ApoE is sort of like the gatekeeper that lets all of these remnants in to the hepatocytes, so they get re-uptaken by the liver so that they can be recycled throughout this system.
Now, how are you going to remember that? Because it's very, very important. Well, I say that ApoE, ApoE eats the remnants. So it eats up the remnants, it takes them back up, recycles them through the system.
So here's a chart where we're going to talk and summarize quickly about the different apolipoproteins, their function, and the Dirty Medicine mnemonic. So we spoke on ApoB-48, that mediates the secretion of chylomicrons from the GI system into the lymphatic system. We talked about ApoC-II, that hydrolyzes the conversion of triglycerides into fatty acids for absorption by activating LPL. As an aside, we also said that insulin activates LPL. And ApoE mediates the reuptake of all of the different remnants. The mnemonics are shown here. Remember your B-48 chylomicron bomber, ApoC-II, two C's, cuts and cleaves, and ApoE, ApoE eats the remnants.
So here's where we are in summary so far. We're going to close out part two of lipid transport by talking about one more step. So the chylomicron, at this point, has everything that it needs, and now it's going to convert itself into a chylomicron remnant to be taken into the liver. Remember, ApoE, ApoE eats the remnants. So the gatekeeper in that process is ApoE. So our big purple chylomicron goes to our little baby chylomicron remnant, and that remnant goes into the hepatocyte, into the liver, to be recycled.
For this process to continue, we're going to stop part two here because I don't want to give you too much information at once. But remember our summary slide of the different apolipoproteins. And in part three of lipid transport, we'll wrap up by talking about the other two really high-yield apo-lipoproteins that are involved in lipid transport.