Biochemistry 401 Lecture 30 Today we re going to talk about cholesterol transport We re going to talk about the origin function and fate of lipoprotein particles good cholesterol versus bad cholesterol and then we re going to talk about lipoprotein particles and disease including atherosclerosis and metabolic disorder So let s get started Lipoprotein particles are comprised of both lipids and proteins just as the name suggests The lipids include phospholipids triacylglycerols cholesterols and cholesterol esters and other lipids such as lipid soluble vitamins The proteins are called apolipoproteins and sometimes they re called apoproteins Apolipoproteins serve many purposes They help to organize the lipoprotein particle and they help to target it to the right place Some apolipoproteins also act as enzyme cofactors Lipoprotein particles have a polar exterior that faces the aqueous solution and a hydrophobic interior Lipoprotein particles are constructed such that the polar groups are situated facing the outside toward the aqueous solution and the hydrophobic portions face the inside of the lipoprotein particle and that s as you would expect Cholesterol is oriented with the hydroxyl facing the outside and the ring structure and long hydrocarbon tail pointing toward the inside Here we see phosphatidylethanolamine The long hydrocarbon tails are facing inward and the ester linkage and phosphate alcohol head group are pointing toward the outside The same thing is true for triacylglycerols The fatty acids are pointing toward the inside of lipoprotein particle and the ester linkages are pointing toward the outside This makes the ester linkages accessible to lipases and this is important in the hydrolysis of triacylglycerols Lipoprotein particles also contain apolipoproteins and these are also found toward the outside And packed in the center of lipoprotein particles we find cholesterol esters This is cholesterol that has been acylated A fatty acid has been added at the hydroxyl so that it can pack more tightly into the center of the lipoprotein particle Plasma lipoproteins we re originally isolated and characterized based on their relative densities Plasma lipoproteins are shown in the figure below and are listed in this chart The name of the plasma lipoprotein is shown first then its density its diameter the type of apolipoprotein it contains its physiologic role in the body and its percent composition of triacylglycerols cholesterol esters 1 cholesterol phospholipids and protein We re going to start with chylomicrons These are the least dense and they have the highest diameter They contain the apolipoprotein B48 and C and E Chylomicrons primarily contain triacylglycerols of dietary origin and therefore the physiological role of chylomicrons is to transport fats The rest of these plasma lipoproteins are constructed in the liver They range from very low density lipoprotein which is the least dense of those that are generated the liver all the way down to high density lipoprotein particles They vary not only in their density and diameter but also in their physiological role For instance high density lipoprotein is what you may have heard referred to as good cholesterol This is a lipoprotein particle that is engaged in reverse cholesterol transport High density lipoproteins take cholesterol from the tissues and bring it back to the liver The rest of these the very low density lipoproteins intermediate density lipoproteins and low density lipoproteins all carry endogenous lipids from the liver to the tissues Very low density lipoproteins are constructed in the liver and like chylomicrons they primarily contain triacylglycerols Their role is to carry endogenous fat in the body and to transport it to the tissues primarily the muscles and the adipose tissue and as more and more triacylglycerols are given off very low density lipoproteins become intermediate density lipoprotein particles As they give off more of their lipids they become smaller and therefore more dense Intermediate density lipoproteins are then turned into low density lipoprotein particles and these are primarily involved in cholesterol transport They primarily contain cholesterol esters and so low density lipoprotein is known as the bad cholesterol It is involved in transport of cholesterol originally from the liver to the tissues Now the apolipoproteins that are found in chylomicrons differ from those that are found in lipoprotein particles that arise in the liver Chylomicrons contain B48 for instance Those lipoprotein particles that contain endogenous lipids contain B100 apolipoprotein And so what you need to know about this chart There s a lot of inflammation Well you need to know the names of the plasma lipoproteins and whether they re larger or smaller in comparison to one another and whether they re more dense or less dense in comparison with each other You also need to know what sort of B apolipoprotein they contain and which component has the highest percentage composition in each lipoprotein particle For instance in chylomicrons and in very low density lipoproteins the component with the highest percentage are triacylglycerols In intermediate density lipoprotein it s about a 50 50 split between triacylglycerol and cholesterol esters whereas in low density lipoprotein particles this is cholesterol ester and in high density lipoprotein it s protein and 2 that s it Please do not memorize these numbers You do not have to memorize the numbers I hope this helps So why is it that chylomicrons which are formed in the small intestines have a different apolipoprotein B than those lipoprotein particles that are constructed in the liver The small intestine contains an enzyme a deaminase that removes the amino group in cytosine to form uracil This introduces a stop codon into the messenger RNA Therefore the ribosome stops short and translates a shorter B apolipoprotein In fact it s only about half as long as apoB100 This is an intestinal specific apolipoprotein and it s only found in chylomicrons Now chylomicrons as we said are formed in the small intestines and they have three stages of development They start off as a nascent chylomicron They have all their lipids but they don t have all their proteins and we ll talk about that in just a minute and therefore they re not functional These nascent chylomicrons are found in the intestines and in the lymphatic vessels and are found early on in the bloodstream In the bloodstream
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