Chylomicrons diameters

The triacylglycerols are incorporated into a heterogeneous population of spherical lipoprotein particles known as chylomicrons (diameter, 75-600 nm) that contain about 89% triacylglycerol, 8% phospholipid, 2% cholesterol, and 1 % protein. Phospholipids of the chylomicron arise by de novo synthesis (Chapter 19) or from reacylation of absorbed lysolecithin. Cholesterol is supplied by de novo synthesis (Chapter 19) or is absorbed. The protein apolipoprotein B-48 (apo B-48) forms a characteristic protein complement of chylomicrons and is synthesized in the enterocyte. Synthesis of apo B-48 is an obligatory step in chylomicron formation. Absence of apo B-48 synthesis, as in the rare hereditary disease abetalipoproteinemia,... 

Four main classes of Upoproteins are present in normal human plasma (for reviews, see refs. 1-3). The largest of these, the chylomicrons (diameter 800-5000 A, density < 0.95 g/ml they remain at the origin during electrophoresis. Fig. 1), contain predominantly dietary triglycerides and a spectrum of apoUpoproteins (Fig. 2). Chylomicrons are manufactured in the intestines from dietary Upids, secreted into the lymph, and subsequently enter the blood circulation. Since chylomicrons are too large to cross the vascular endothelium, they are degraded in plasma by the enzyme Upoprotein lipase which is present on the surface of endotheUal cells that... 

Lipoproteins lipid-protein conjugates found in cellular membranes, blood plasma, cell cytoplasm and egg yolk. Blood plasma L. are responsible for the transport and distribution of Upids (hormones, dietary lipids from the intestine, fat-soluble vitamins) via the blood and lymph systems. The largest L. are the microscopically visible chylomicrons (diameter 500 nm) these are responsible for the lipemia (milky turbidity) of the blood, which follows the digestion of a fatty meal, and which disappears after about 5 hours. The other L. are always present in the blood the apoproteins in them are produced in the liver. 

Reaction with lipoprotein lipase results in the loss of approximately 90% of the triacylglycerol of chylomicrons and in the loss of apo C (which remrns to HDL) but not apo E, which is retained. The resulting chy-lotnicron remnant is about half the diameter of the parent chylomicron and is relatively enriched in cholesterol and cholesteryl esters because of the loss of triacylglycerol (Figure 25-3). Similar changes occur to VLDL, with the formation of VLDL remnants or IDL (intermediate-density lipoprotein) (Figure 25-4). 

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. 

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. 

RGURE 17-2 Molecular structure of a chylomicron. The surface is a layer of phospholipids, with head groups facing the aqueous phase. Triacylglycerolssequestered in theinterior (yellow) make up more than 80% of the mass. Several apolipoproteins that protrude from the surface (B-48, C-lll, C-ll) act as signals in the uptake and metabolism of chylomicron contents. The diameter of chylomicrons ranges from about 100 to 500 nm. 

If the remarkable rapidity and specificity of uptake of the chylomicron remnant particles by these two different endocytic pathways reflects a similar uptake pattern for LCM as proposed, then one would probably expect a large portion of the LCM size distribution to be in the same diameter range as found with chylomicron remnants. The remnant particles are of particular interest because their size distribution is known (cf. below) to display both a wider range (i.e., more polydispersity) and larger sizes than either LDL or modified LDL particles accordingly, this polydispersity provides more information about the size constraints or limits imposed by the endocytic pathways involved in the active uptake of chylomicron remnant particles and probably also of LCM. The diameter range for the native chylomicron remnants has already been determined by other investigators, from in vivo and in... 

In the intestinal mucosal cells, the triacylglycerols are resynthesized from fatty acids and monoacylglycerols and then packaged into lipoprotein transport particles called chylomicrons, stable particles ranging from approximately 180 to 500 nm in diameter (Figure 22.5). These particles are composed mainly of triacylglycerols, with apoprotein B-48 as the main protein component. Protein constituents of lipoprotein particles are called apolipoproteins. Chylomicrons also function in the transport of fat-soluble vitamins and cholesterol. 

Apo C-II activates lipoprotein lipase. A diagram of a chylomicron particle and a VLDL particle about to pass through a capillary is shown below. Chylomicrons are relatively large, having a diameter of 500 nm, while VLDLs are smaller, with a diameter of 100 nm. Lipoprotein lipase is shown as small dots adhering to the lumen of the capillary, and the chylomicron is shown contacting one of the lipases (Goldberg, 1996), The released free fatty aeids (FFA) are taken up and used by cells that reside near the capillary ... 

Synthesis and secretion of chylomicrons are directly linked to the rate of dietary fat absorption. When fat is absent from the diet, small chylomicrons with a diameter of about 50 nm are secreted at a rate of approximately 4 g of triacylglycerol per day. On a high-fat diet, the mass of lymphatic triacylglycerol transport may increase 75-fold, owing partly to greater production of chylomicrons but primarily to a dramatic increase in size of the particles, which may have diameters of 1200 nm, and a 16-fold increase in the amount of triacylglycerol within their core. 

As the core triacylglycerols of a chylomicron are depleted, often reducing its diameter by a factor of 2 or more, the surface components are also modified. A substantial portion of the phospholipids and of apo A and C is transferred to HDL. The C apoproteins thus cycle repeatedly between newly produced chylomicrons and HDL. The chylomicron remnant is consequently rich in cholesteryl esters and apo B-48 and E. 

Chylomicrons are the largest plasma lipoproteins because they contain the largest percentage of lipid molecules. In contrast, HDL have a relatively small diameter because their high protein content makes them dense. 

The classification into chylomicrons (CM), very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins is based on their relative contents of protein and lipid that determine the densities of these lipoprotein classes. CM have only 1-2% protein while HDL have about 50% protein by weight. The diameters of lipoproteins are inversely correlated with their densities and range from about 6000 A for CM to 70 A for the smallest HDL (Fig. 1). 

Fig. 2. Negative-staining electron micrographs of human plasma lipoproteins (diameters 10-1(KX) nm). The laigest particles [chylomicrons (Chylo) and VLDLs] contain a higher ratio of lipid to protein, and are therefore less dense, than low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs) that contain relatively more protein. Photograph courtesy of Dr. R. Hamilton, University of California at San Francisco, with permission.

A specific type of interaction between lipids and proteins is found in lipoproteins which transport triglycerides and cholesteryl esters in the plasma of mammalians. The largest lipoproteins, chylomicrons with a diameter between 800 A and 5000 A, and very-low-density lipoproteins (VLDL), with a diameter of 300-800 A, resemble emulsion droplets with a core of non-polar lipid and a surface coat of phospholipids and proteins (cf. Brown et ai, 1981). A physical characterization of chylomicrons has been reported (Parks et al.y 1981). Most of the plasma cholesterol occurs in low-density lipoprotein (LDL) which is a particle with a diameter of 200 A. The core consists of almost pure cholesteryl esters and a surface coat of a phospholipid monolayer and four tetrahedrally arranged apoproteins (Gulik-Krzywicki et aly 1979). The smallest particle, high-density lipoprotein (HDL), is a kind of molecular lipid-protein complex. 

Determined from the calibration of the column obtained for the standard samples of known particle diameter (24). C chylomicrons, VLDL very low density lipoproteins, LDL low. density lipoproteins, HDL high density lipoproteins, HDLsub HDL subfractions. 

Electron microscopic studies have shown that in the liver of the rat the sinusoids are lined by a discontinuous endothelium. The cells have no well defined basement membrane and may be separated from each other by gaps of several thousand Angstrom units. When particles of smaller diameter than these gaps are introduced into the circulation they can enter the subendothelial space of Disse and come into direct contact with the microvilli on the surface of the hepatic parenchymal cells (Bennet et al. 1959). Following the intravenous injection of chyle, chylomicrons could be seen within the lumen of hepatic sinusoids, within gaps of their endothelial lining and within the subendothelial space (French 1963). 

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