welcome back to dirty medicines 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 entero sites in the small intestine that's where we left off so with part 2 of lipid transport we're gonna 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 ok 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 april lipoprotein receptor act on it and that's depicted here with an orange triangle this is a po b48 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 that is that there are what is referred to as a po lipoproteins that act on various players in this biochemical pathway now if you're overwhelmed by the different ways that these aprile lipoproteins are written for example AVO b48 a bo c2 a po e etc etc don't worry because for each of the aprile lipoproteins 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 in April lipoprotein come into play so the way that you're going to remember what the a po b48 April lipoprotein does is b48 should make you think of the b48 bomber of famous aircraft the b48 bomber now instead of this airplane dropping bombs I want you to amass that it drops chylomicrons or kylo mike bombs if you will so instead of regular bombs the b48 bomber is gonna drop chylomicrons from the intestine or from the GI system into the lymphatic system and that's just the role that a po b48 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 no downstream where they're supposed to end up so if on test day you have a question about what a po b48 role in biochemistry is you need to think the b48 bomber dropping bombs are dropping the chylomicron bomb on the lymphatic system so that is the role of a PO e 48 so here's where we are the chylomicrons were formed in the intestines and then a po b 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 gonna 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 a po b48 Apryl lipoprotein on it but it's about to get some more Apryl lipoproteins 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 Apryl lipoproteins on a chylomicron and those Apryl lipoproteins 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 April lipoproteins 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 chillin enjoying life with its little a PO b48 hat it's going to donate HDL that is is going to donate a possi to end a PO a3 to the chylomicrons shown here so the chylomicron is still in the systemic circulation it's just gonna 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 a possi two and a bowi now when this happens the chylomicron now has three right three different April lipoproteins sitting on its shell if you will it's got a PO b48 shown here in orange it's got a po e shown here and that sort of mustard mucus color and it's got a PO si tu shown here and that's sort of maroonish color okay so here's where we are our purple chylomicron has three aple lipoproteins on it it's got a PO b48 which came from the GI system and sort of helped the chylomicron reach the lymphatic system and then it was donated a po e and a PO si to 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 a PO b48 does remember that b48 should remind you of the famous aircraft the b48 bomber which drops the chylomicron bomb on the lymphatic system but I need to talk to you first about what a PO si tu does as well as a PO e 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 pneumonic okay so a possi 2 is going to activate what's known as lipoprotein lipase which is commonly referred to in biochemistry as LPL so a bo c 2 mediates the activation of LPL now what LPL does is it actually hydrolyzes the conversion of triglycerides into fatty acids so April c2 on this chylomicron activates LPL and then LPL will hydrolyze and cut those triglycerides into fatty acids for absorption okay so how do you remember what a possi two does well I think about c2 right the two c''s so a possi two cuts and Cleaves a possi to the two c''s a possi two cuts and Cleaves okay not only does it rhyme but it makes sense c2 which means to seize to seize cuts and cleaves okay so a possi two 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 a possi two 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 one diabetes you're not gonna have weight gain you're gonna have an incredible amount of weight loss so now we've got two awesome mnemonics that tell us what - April lipoproteins do a PO b48 the b48 bomber that drops the chylomicron bomb so again AVO be 48 media it's the secretion of the chylomicrons from the intestine / the GI tract into the lymphatic system a possi - turns on lipoprotein lipase which hydrolyzes and cuts triglycerides into fatty acids to be absorbed by the body so a possi - to seize cuts and cleaves now let's talk about a PO e so the other piece the other April lipoprotein that came from HDL was a bowi now a bowi has an incredibly important role in this system that cannot be understated I'm going to simplify what I'm about to say it's the best of my ability but this is a very complex topic in terms of how a PO e 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 a PO E is the receptor that does that recycling so a bowi is sort of like the gatekeeper that lets all of these remnants in to the hepatocytes so they get re up taken 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 a po e a po 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 dipper different April lipoproteins their function and the dirty medicine mnemonic so we spoke on April be 48 that mediates the secretion of chylomicrons from the GI system into the lymphatic system we talked about a possi - 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 a po e mediates the reuptake of all of the different remnants the mnemonics are shown here remember your b48 chylomicron bomber april c22 sees cuts and cleaves and a po e a po eats the remnants so here's where we are in summary so far we're gonna 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 now remember a po e a po eats the remnants so the gatekeeper in that process is a po y 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 gonna 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 April lipoproteins and in part three of lipid transport we'll wrap up by talking about the other two really high yield a pole I po proteins that are involved in lipid transport