welcome back to dirty medicines dirty biochemistry series in this video we're going to cover the third and final part of lipid transport if you've been watching the first two parts of lipid transport and I hope that you have because we're building upon each previous video then you probably already have a great understanding of how lipid transport progresses through the body where we left off was on this slide to briefly summarize the chylomicron had moved from the intestine into the lymph it had then moved from the lymph into the systemic circulation HDL came along and loaded the chylomicron with a PO c2 and a bowi the Carlow micron already had a PO b48 on it and in the previous video we discussed the role of each of those Apryl lipoproteins individually and I gave you guys a really awesome pneumonic for each of them to help you remember their high-yield function then the chylomicron left the systemic circulation and went in to the liver in the form of a chylomicron remnant depicted on this slide the big purple chylomicron turns into the small chylomicron remnant own here with that small purple circle in the liver that is a very quick and very rough summary of where we've left off so far in lipid transport we're gonna pick up the pathway from this point onward part three in this video we'll discuss the important high-yield two remaining Apryl lipoproteins as well as where lipid transport goes once the chylomicron remnants into the liver now as the chylomicrons turn into their remnants and go into the liver there's this dynamic process since that this dynamic process that's taking place where additional lipoproteins are actually secreted by the liver the first piece that's going to come out of the liver is called very low density lipoprotein this is referred to in question banks and review textbooks as VLDL on this slide and in this series VLDL will be depicted as a pink square now inside a VLDL you have triglycerides and cholesterol so this is another lipoprotein that just carrying lipids the VLDL has a unique April lipoprotein that sits on its shell if you will and that April lipoprotein is a poby 100 now I'm not gonna tell you right now what April b100 does because I need to continue to show you the biochemical pathway here and then we'll come back to April b100 and discuss its function and of course I'll give you an awesome mnemonic to help you memorize its high-yield function so if I can sort of take the liver and the VLDL we're gonna start from this part of the pathway so forget everything that happened in the first two parts with the chylomicrons what I want you to focus on now are the details of what happens when the liver secretes VLDL so again VLDL comes out it's got triglycerides and cholesterol inside of it and it has a Polly 100 on its shell now as VLDL progresses through this pathway HDL comes along once again in the previous video we saw that HDL is an extremely important part of this pathway and the reason that it is so important and the reason that it's referred to as the quote good fat is because it's loading different pieces of this lipid biochemistry with a PO e and a PO see - I've discussed all of this in the previous video so watch that again if you need a refresher but just like it did this in the previous video HDL is also going to load these April lipoproteins onto the VLDL so as you see here on this slide a pony show Ninh our mucus color and a plus c2 shown in the reddish color are going to be loaded by HDL on to VLDL so they're gonna appear on VLDL now at this point the VLDL has three april lipoproteins on it right it has the April be 100 which I'm going to tell you about in a little bit and it has a PO II and April c2 and recall from the previous video that the role of a possi 2 is to activate LPL to hydrolyze and convert triglycerides to fatty acids for absorption so that's going to be happening here just like other pieces in this pathway that we've seen the a possi 2 on the VLDL carries the same exact function now once that's happening VLDL is going to is going to convert itself into something IDL's so this is an intermediate density lipoprotein so we had very low density lipoprotein VLDL and now we have the intermediate density lipoprotein so the only thing that's really changing in terms of the naming convention is the density of these different lipoproteins so now we have ideal an IDL retains the a PO a that was put on to its predecessor VLDL and it retains the APO b100 that was already on its predecessor the LDL and April c2 is doing its job by activating LPL and converting the triglycerides into fatty acids so for the purposes of this discussion and to simplify this pathway VLDL turns into IDL and now it has a PO e and April be 100 on its shell now at this point the IDL can enter the liver and what doesn't enter the liver will be converted into the next lipoprotein which is known as LDL this is low-density lipoprotein now LDL is also known as the bad cholesterol or the bad fat and you'll soon see why in the dirty medicine biochemistry dirty biochemistry series LDL will be depicted by this small green square so IDL can either enter the liver or be converted directly into LDL and a little bit of the LDL can actually come out of the liver itself in either scenario the a PO b100 will still be on the LDL now recall that that a PO be 100 was on the IDL before it and the VLDL before that so there's obviously an important role for this April be 100 because it's being you know retained as VLDL converts to ideal and it's ideal converts to LDL so what that will be 100 actually mediates is the attachment of LDL to the LDL receptor and that LDL receptor is what allows the LDL to undergo endocytosis into peripheral cells so if we can sort of clip LDL out of the slide and put it next to a peripheral cell this is what I'm referring to so you have LDL also known as the bad cholesterol or the bad fat and cholesterol is really not a problem until it gets into certain cells so if if on the right you have this circular peripheral sell the only way that LDL can get into that cell is for it to interact with the LDL receptor right there has to be a receptor on the surface of the cell that binds to the LDL hence the name LDL receptor now the way that the LDL receptor recognizes the LDL is by recognizing a PO be 100 so eight will be 100 is what is recognized by the LDL receptor so if these two parallel blue lines represent the LDL receptor then it's a PO be 100 that's sort of acting like the key that fits nicely into that LDL receptor and informs the peripheral cell hey my name is LDL I'm here to be inside of you sounds funny but that's exactly how it works so when this happens you have endocytosis of LDL into this peripheral cell and now LDL with its little a PO be 100 hat is sitting inside of the peripheral cell and this is the process whereby triglycerides and cholesterol arrive at peripheral cells from the liver so recall that the LDL came from the liver where it was converted from IDL which also went to the liver so really these triglycerides in these cholesterol are coming from the liver and they're going to peripheral cells because LDL the carrier is going undergoing endocytosis into the peripheral cells so that's the reason that LDL is the bad fat because it's taking triglycerides and cholesterol from the liver where they're stored and it's putting them into the peripheral cells and this is where LDL can be really harmful and caused disease okay so let's pause for a second and take a step back and appreciate the big picture we talked about that V LDL is converted to IDL IDL either enters the liver and then becomes LDL or is directly converted to LDL in either case as this whole transformation of VLDL to IDL to the liver to LDL takes place all of those products retain this april-b 100 hat so the high yield summary here is that if you see a PO be 100 you should know that it mediates the ultimate entry of LDL into peripheral cells so LDL comes from the liver and gets into peripheral cells and brings with it triglycerides cholesterol fat from the liver into peripheral cells because a PO b100 interacts with the LDL receptor that is the big takeaway point here that you absolutely need to know it's incredibly high yield so the way that you should remember this and the dirty medicine mnemonic is that a PO be 100 makes you gain 100 pounds right so April be 100 is what puts the fat from your liver into the peripheral cells and makes you fat right it puts cholesterol and triglycerides and lipids etc all those buzzwords that all mean fat it goes from the liver into your peripheral cells and that's what makes you gain 100 pounds so april-b 100 again just to really hammer this home is what interacts with the LDL receptor and causes endocytosis of LDL along with its stored lipid content in two peripheral cells so a PO be 100 makes you gain 100 pounds here's the slide that we had in the previous video we had already spoken about a PO b48 a PO c2 and apoE their function is listed on this slide as well as the dirty medicine daemonic see the previous video if you need more information or a brief refresher but now let's update this slide and add a PO be 100 so again the function of a PO be 100 is that it binds the LDL receptor for endocytosis into the peripheral cells and the mnemonic here are dirty medicine awesome mnemonic is that a PO be 100 makes you gain 100 pounds and the wheat the reason that it does this is because April be 100 is what interacts with the LDL receptor to allow LDL and all of its associated fat content to get in to the peripheral cells now there's one more April lipoprotein that we need to cover which we'll fill in the last row on this slide and in order to really appreciate the function of that next april lipoprotein we have to talk about the activation of HDL so recall from the previous video and even the beginning of this video that HDL is known as the good cholesterol the reason that it's the good cholesterol is because it has a po e and a PO si tu sitting on its shell and what it does is it carries a PO II in a possi too and loads it onto different players in this pathway allowing them to be re up taken that's a bowie does and through a possi to to cleave triglycerides into fatty acids for absorption now these functions are crucial to the normal physiology of our human bodies and without them we would have a ton of disease so HDL is very important now what happens here is that before HDL is formed in its final form that you see here on this slide it's actually first secreted from the liver and the small intestine in what is called nascent HDL form so but this basically means is that it's like baby HDL right it's the precursor to HDL that's not yet activated into full-blown mature HDL and when I use the word mature HDL I'm really just referring to the HDL that we've already talked about right the final product that has the apoE in a possi to on it donating those April lipoproteins to players in this lipid transport pathway so when you see this slide and you see the small HDL what that really means is mature HDL but before you get mature HDL you get nascent HDL so immature or baby HDL and there's a very high yield enzyme that activates or converts nascent HDL into mature regular HDL and that enzyme is called lecithin cholesterol acyl transferase also known as lkl see a tea now the final lipoprotein April lipoprotein that we need to talk about is what is known as a PO a 1 and the reason that April a 1 is so high yield and so important to understand is because it is actually the April lipoprotein that activates l cat so April a 1 comes along and activates lecithin cholesterol acyl transferase also known as L cat which is to say that April a 1 is what mediates the conversion of immature HDL into mature HDL so without April a 1 you never get HDL so you never get the good cholesterol that loads a po e and a possi 2 onto the various players in this lipid transport pathway so as I'm sure you can see by looking at this slide April a 1 is really freakin important right without it you cannot get the good cholesterol you use a Bowie and a possi too because without April a one you would never form the mature HDL so what is the dirty medicine mnemonic for remembering this important pathway well the way that you should remember this is by looking at the letter A because April a1 is the only a PO that has a in the name so the way that I remember this is that a PO a1 activates awesome fat which activates awesome fat awesome because HDL is that awesome or the good fat so a4 activates a for awesome remember that eighth or a one activates awesome fat so it activates the fat that is the good fat which is to say that it activates HDL by working on the L cat okay so that's what a PO a1 does and if we fill in this chart for completeness sake we've now touched on the five high-yield April lipoproteins again remember that April a 1 activates L cat to convert nascent HDL into mature HDL in the dirty medicine mnemonic is that April a 1 activates awesome fat a PO be 100 we already talked about in this video a PO be 100 makes you gained 100 pounds because April be 100 is what mediates the endocytosis of LDL or the bad cholesterol into peripheral cells so it makes you fatter the last thing that I want to touch on before we conclude this video is one really high-yield differentiating point that's really easy for medical students to mix up so it's incredibly important to understand that LDL is taking the cholesterol from the liver to the periphery which is to say that it goes from the liver to the peripheral cells in the body but HDL is taking the cholesterol from the peripheral cells and bringing it back to the liver so the HDL in addition to loading a pony in a possi to under various players in this pathway is actually sucking up some of the fat some of the cholesterol that is existing in your peripheral cells and putting it in the liver so that it doesn't damage your cells so that's why HDL in addition to all the reasons that we've already talked about is the good fat and LDL is the bad fat because it's taking the fat out of the liver and putting it in the periphery where it really should not build up too much the way that I remember this is that HDL is hepatic delivery so H delivers those fats to the liver so hepatic delivery H and hepatic D and L and delivery so HDL is where the fat undergoes hepatic delivery so make sure you understand that LDL is from periphery to liver and that LDL is from liver to periphery that point can be confused very easily if you overlook some details here but guys and gals that's it for lipid transport we've now touched on a very high yield pathway that's very complex and it's very confusing because it's got all these different Apryl lipoproteins it's got all of these different pieces that all sound the same right VLDL sounds like IDL sounds like LDL sounds like HDL there's a lot of D's a lot of LS you know you have to understand the fine points here but if you conclude each video by looking at my summary slides understanding some differences keeping the big picture in mind and remembering my dirty medicine mnemonics I think that you'll get most of your points correct on test day