Liver chylomicron

B-48 2152 241 Intestine Chylomicron formation ligand for liver chylomicron receptor... 

Plasma Lipoproteins. The plasma lipids are transported by four major lipoprotein classes. The plasma lipoproteins are synthesized and secreted only in the intestine and liver. Chylomicrons, the richest in triglyceride, are synthesized in the small intestine and transport dietary (exogenous) triglyceride and cholesterol. Very low density (prebeta) lipoproteins (VLDL)... 

Apo-E (chylomicron remnant) Liver Chylomicron remnants HDL-with apo-E (HDL ) Apo-E Not subject to marked down-regulation Uptake of chylomicron remnants and cholesterol-loaded HDL-with-apo-E Delivery of cholesterol to the liver for excretion... 

FIGURE 35-1 The miyor pathwi s involved in the metabolism of chylomicrons synthesized by the intestine and VLDL synthesized by the liver. Chylomicrons are converted to chylomicron remnants by the hydrolysis of their triglycerides by LPL. Chylomicron remnants are rapidly cleared from the plasma by the liver. Remnant receptors include die LDL receptor-related protein (LRP), LDL, and perhaps other receptors. FFA released by LPL is used by muscle tissue as an energy source or taken up and stored by adipose tissue. FFA, free fatty acid HL, hepatic lipase IDL, intermediate-density lipoproteins LDL, low-density lipoproteins LPL, lipoprotein lipase VLDL, very-low-density lipoproteins. 

HDL and VLDL are assembled primarily in the endoplasmic reticulum of the liver (with smaller amounts produced in the intestine), whereas chylomicrons form in the intestine. LDL is not synthesized directly, but is made from VLDL. LDL appears to be the major circulatory complex for cholesterol and cholesterol esters. The primary task of chylomicrons is to transport triacylglycerols. Despite all this, it is extremely important to note that each of these lipoprotein classes contains some of each type of lipid. The relative amounts of HDL and LDL are important in the disposition of cholesterol in the body and in the development of arterial plaques (Figure 25.36). The structures of the various... 

The livers and intestines of animals are the primary sources of circulating lipids. Chylomicrons carry triacylglycerol and cholesterol esters from the intestines to other tissues, and VLDLs carry lipid from liver, as shown in Figure 25.38. At... 

TRIACYLGLYCEROL IS TRANSPORTED FROM THE INTESTINES IN CHYLOMICRONS FROM THE LIVER IN VERY LOW DENSITY LIPOPROTEINS... 

There are striking similarities in the mechanisms of formation of chylomicrons by intestinal cells and of VLDL by hepatic parenchymal cells (Figure 25—2), perhaps because—apart from the mammary gland—the intestine and liver are the only tissues from which particulate lipid is secreted. Newly secreted or nascent chylomicrons and VLDL contain only a small amount of apolipoproteins C and E, and the frill complement is acquired from HDL in the circulation (Figures 25—3 and 25-4). Apo B is essential for chylomicron and VLDL formation. In abetalipoproteinemia (a rare disease), lipoproteins containing apo B are not formed and lipid droplets accumulate in the intestine and liver. 

The clearance of labeled chylomicrons from the blood is rapid, the half-time of disappearance being under 1 hour in humans. Larger particles are catabolized more quickly than smaller ones. Fatty acids originating from chylomicron triacylglycerol are delivered mainly to adipose tissue, heart, and muscle (80%), while about 20% goes to the liver. However, the liver does not metabolize native chylomicrons or VLDL significantly thus, the fatty acids in the liver must be secondary to their metabolism in extrahepatic tissues. 

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)... 

HDL is synthesized and secreted from both liver and intestine (Figure 25—5). However, apo C and apo E are synthesized in the liver and transferred from fiver HDL to intestinal HDL when the latter enters the plasma. A major function of HDL is to act as a repository for the apo C and apo E required in the metabohsm of chylomicrons and VLDL. Nascent HDL consists of discoid phosphohpid bilayers containing apo A and free cholesterol. These hpoproteins are similar to the particles found in the plasma of patients with a deficiency of the plasma enzyme lecithimcholesterol acyltransferase (LCAT) and in the plasma of patients with obstructive jaundice. LCAT—and the LCAT activator apo A-I— bind to the disk, and the surface phosphohpid and free cholesterol are converted into cholesteryl esters and... 

Four major groups of lipoproteins are recognized Chylomicrons transport lipids resulting from digestion and absorption. Very low density lipoproteins (VLDL) transport triacylglycerol from the liver. Low-density lipoproteins (LDL) deliver cholesterol to the tissues, and high-density lipoproteins (HDL) remove cholesterol from the tissues in the process known as reverse cholesterol transport. 

Chylomicrons and VLDL are metabolized by hydrolysis of their triacylglycerol, and lipoprotein remnants are left in the circulation. These are taken up by liver, but some of the remnants (IDL) resulting from VLDL form LDL which is taken up by the liver and other tissues via the LDL receptor. 

Hypolipoproteinemias Abetaiipoproteinemia No chylomicrons, VLDL, or LDL are formed because of defect in the loading of apo B with lipid. Rare blood acylglycerols low intestine and liver accumulate acylglycerols. Intestinal malabsorption. Early death avoidable by administration of large doses of fat-soluble vitamins, particularly vitamin E. 

Familial type III hyperlipoproteinemia (broad beta disease, remnant removal disease, familial dysbetalipoproteinemia) Deficiency in remnant clearance by the liver is due to abnormality in apo E. Patients lack isoforms E3 and E4 and have only E2, which does not react with the E receptor. Increase in chylomicron and VLDL remnants of density < 1.019 (P-VLDL). Causes hypercholesterolemia, xanthomas, and atherosclerosis. 

This approach can be used only for fat-soluble compounds that follow the same lymphatic route to be transported to the liver as carotenoids. The bioavailability of the compound of interest is determined by monitoring the appearance of the compound and its newly formed intestinal metabolites in the postprandial chylomicron fraction of plasma [also called the density < 1.006 kg/L fraction or triglyceride-rich lipoprotein (TRL) fraction because it is generally a mixture of chylomicrons (CMs) and very low density lipoproteins (VLDLs)] as a function of the time after ingestion. 

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... 

Chylomicrons leave the absorptive cell by way of exocytosis. Because they are unable to cross the basement membrane of the blood capillaries, the chylomicrons enter the lacteals, which are part of the lymphatic system. The vessels of the lymphatic system converge to form the thoracic duct that drains into the venous system near the heart. Therefore, unlike products of carbohydrate and protein digestion that are transported directly to the liver by way of the hepatic portal vein, absorbed lipids are diluted in the blood... 

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