Chylomicrons remnants

Chylomicron remnants Chylomicrons 45-150 <1.006 6-8 92-94 Triacylglycerol, phospholipids, cholesterol B-48, E... 

The main apohpoprotein of LDL (P-lipopro-tein) is apohpoprotein B (B-lOO) and is found also in VLDL. Chylomicrons contain a truncated form of apo B (B-48) that is synthesized in the intestine, while B-lOO is synthesized in the hver. Apo B-lOO is one of the longest single polypeptide chains known, having 4536 amino acids and a molecular mass of 550,000 Da. Apo B-48 (48% of B-lOO) is formed from the same mRNA as apo B-lOO after the introduction of a stop signal by an RNA editing enzyme. Apo C-1, C-11, and C-111 are smaller polypeptides (molecular mass 7000— 9000 Da) freely transferable between several different hpoproteins. Apo E is foimd in VLDL, HDL, chylomicrons, and chylomicron remnants it accounts for 5— 10% of total VLDL apohpoproteins in normal subjects. 

Chylomicron remnants are taken up by the liver by receptor-mediated endocytosis, and the cholesteryl esters and triacylglycerols are hydrolyzed and metabolized. Uptake is mediated by a receptor specific for apo E (Figure 25-3), and both the LDL (apo B-lOO, E) receptor and the LRP (LDL receptor-related protein)... 

LPL found on the endothelial surfaces of the blood capillaries) to produce chylomicron remnants, which are then removed from the circulation by specific remnant receptors located on parenchymal liver cells. VLDLs are secreted by the liver. Following their secretion in blood, VLDLs undergo metabolism in a way... 

The use of LDL and other lipoproteins in drug targeting has been reviewed [170,172], Damle et al. [173] have shown that radiopharmaceuticals, such as iopanoic acid, a cholecystographic agent, could be incorporated in chylomicron remnants by esterification with cholesterol and used for liver imaging. About 87% of the chylomicron remnant-loaded iopanoic acid accumulated in the liver within 0.5 hour after administration, compared with 31% accumulated using a... 

In the enterocyte, provitamin A carotenoids are immediately converted to vitamin A esters. Carotenoids, vitamin A esters, and other lipophilic compounds are packaged into chylomicrons, which are secreted into lymph and then into the bloodstream. Chylomicrons are attacked by endothelial lipoprotein lipases in the bloodstream, leading to chylomicron remnants, which are taken up by the liver (van den Berg and others 2000). Carotenoids are exported from liver to various tissues by lipoproteins. Carotenes (such as (3-carotene and lycopene) are transported by low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), whereas xanthophylls (such as lutein, zeax-anthin, and (3-cryptoxanthin) are transported by high-density lipoproteins (HDL) and LDL (Furr and Clark 1997). 

In capillaries of adipose tissue (and muscle), apoC-II activates lipoprotein lipase, the fetty adds released enter the tissue for storage, and the glycerol is retrieved by the liver, which has glycerol kinase. The chylomicron remnant is picked up by hepatocytes through the apoE receptor thus, dietary cholesterol, as well as any remaining triglyceride, is released in the hepatocyte. 

The metabolism of VLDL is very similar to that of chylomicrons, the major difference being that VLDL are assembled in hepatocytes to transport triglyceride containing fatty acids newly synthesized from excess glucose, or retrieved from the chylomicron remnants, to adipose tissue and musde. ApoB-100 is added in the hepatocytes to mediate release into the blood. Like chylomicrons, VLDL acquire apoC-II and apoE from HDL in the blood, and are metabolized by lipoprotein lipase in adipose tissue and musde. 

Endocytosis of chylomicron remnants with residual dietary cholesterol... 

Cholesterol mobilised in this way, as well as that absorbed from the intestine, is taken up by the liver from LDL and chylomicron remnants, via receptors on... 

The rationale for this type of contrast agent is to use the endogenous metabolic pathway of lipid metabolism in the liver for the transport of iodinated substances. Chylomicron remnants are naturally occurring lipoproteins in the blood that are responsible for the transport of lipids into the liver. Three different mechanisms for this transport are discussed direct uptake by the low-density lipoprotein receptor transport to the low-density lipoprotein receptor-related protein (LRP) mediated by heparan sulfate proteoglycan (HSPG) or direct HSPG-LRP uptake and direct HSPG uptake. One of the prerequisites for particles to be transported by these mechanisms is a mean diameter of less than 100-300 run. 

Longino MA, Bakan DA, Weichert JP, Counsell RE (1996) Eormulation of polyiodinated triglyceride analogues in a chylomicron remnant-like liver selective delivery vehicle. Pharm Res 13 875... 

Familial dyslipo-proteinemia III IDL 0-VLDL) Chol,TG Decreased plasma clearance of VLDL and chylomicron remnants due to abnormal Apo E (E2 for normal E3). CHD, stroke... 

Triglycerides are removed in extrahepatic tissues through a pathway shared with VLDL that involves hydrolysis by the lipoprotein lipase (LPL) system. Decrease in particle diameter occurs as triglycerides are depleted. Surface lipids and small apoproteins are transferred to HDL. The resultant chylomicron remnants are taken up by receptor-mediated endocytosis into hepatocytes. 

The cholesteryl esters are transferred to VLDL, IDL, LDL, and chylomicron remnants with the aid of cholesteryl ester transfer protein (CETP). Much of the cholesteryl ester thus transferred is ultimately delivered to the liver by endocytosis of the acceptor lipoproteins. HDL can also deliver cholesteryl esters directly to the liver via a docking receptor (scavenger receptor, SR-BI) that does not cause endocytosis of the lipoproteins. 

Familial dysbetalipoproteinemia VLDL remnants, chylomicron remnants increased Fibrate, niacin Fibrate plus niacin, or either, plus reductase inhibitor... 

Plasma lipoproteins can be divided into six major classes (see Fig. 5.2.1). Four of these classes derive from the liver and are present in the plasma of fasted subjects very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). The other two classes of lipoproteins derive from the intestine and are found in the plasma of nor-molipidemic individuals only after a fatty meal (postprandially) chylomicrons and chylomicron remnants. 

Lee SJ, Grosskopf I, Choi SY, Cooper AD (2004) Chylomicron remnant uptake in the livers of mice expressing human apolipoproteins , E2 (Argl58->Cys), and E3-Leiden. J Lipid Res 45 2199-2210... 

ApoE 34,145 Chylomicrons, VLDL, HDL Triggers clearance of VLDL and chylomicron remnants... 

Fate of the remaining chylomicron components After most of tt triacylglycerol has been removed, the chylomicron remnan (which contain cholesteryl esters, phospholipids, apolipoprotein and some triacylglycerol) bind to receptors on the liver (seej 228) and are then endocytosed. The remnants are the hydrolyzed to their component parts. Cholesterol and the nitrogf nous bases of phopholipids (for example, choline) can be req cled by the body. [Note If removal of chylomicron remnants by th liver is defective, they accumulate in the plasma. This is seen i type III hyperlipoproteinemia (also called familial dysbetalipopro teinemia, see p. 229). 

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