Chylomicrons composition

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

D. The lipoproteins include chylomicrons, HDLs, intermediate-density lipoproteins (IDLs), LDLs, and VLDLs, which differ by size, density, and composition of proteins and lipids. 

The plasma lipoproteins are spherical macromolecular complexes of lipids and specific proteins (apolipoproteins or apoproteins). The lipoprotein particles include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They differ in lipid and protein composition, size, and density (Figure 18.13). Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma, and also to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. In humans, the transport system is less perfect than in other animals and, as a result, humans experience a yradual deposition of lipid—especially cholesterol—in tissues. This is a potentially life-threat-en ng occurrence when the lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). 

The chylomicron remnant particles themselves, derived from lipolysis of the larger chylomicrons (cf. above), contain the residual triglyceride and all of the cholesterol and cholesterol ester from the original chylomicrons. This lipid composition of the chylomicron remnant particles is similar to the above-described lipid composition of both LDL particles (cf. Section 14.1) and LCM (cf. Section 12.1). Based upon this molecular similarity, it appears reasonable to expect that injected LCM could also readily bind apo E (i.e., as an alternative to apo B) in the bloodstream. In this case, the proposed LCM binding of apo E should influence the subsequent biodistribution of those LCM via two endocytic pathways specifically, one pathway mediated by the LDL receptor (a.k.a. apo B,E receptor ) (cf. Section 14.1) and the other pathway mediated by the LRP, since both receptor types have a high affinity for apo E (cf. above). 

Imaizumi, K., Fainaru, M., and Havel, R. J., Composition of proteins of mesenteric lymph chylomicrons in the rat and alterations produced upon exposure of chylomicrons to blood serum and serum proteins. J. Lipid Res. 19, 712-722 (1978). 

The different compositions of the plasma lipoproteins give a clue to their function. Essentially, those lipoproteins rich in TAGs are synthesized by the liver (VLDL) and small intestine (chylomicrons) and deliver the neutral fat to extrahepatic tissues (particularly adipose tissue). The fat-depleted lipoproteins have a higher density, and are involved in essential cholesterol transfers. 

The effects of Caprenin, another structured lipid, on chylomicron fatty acid composition and postprandial semm lipid concentrations have also been studied (178). It was found that there is a very low uptake of C8 0, C10 0, and C22 0 into chylomicrons. Moreover, a postprandial lipemia after caprenin is comparable with that produced by other dietary fats as opposed to a fat-free meal. There is considerable... 

Table 6.6 gives compositions for several of the lipoprotein types that have been discussed in this chapter. The high TG contents of chylomicrons 80-95%) and VLDLs 55-65%) are consistent with their function in distributing this eneigy-rich nutrient to various tissues. The low TG content of HDLs implies that these parti cles arc not used to supply energy to cells. 

Fig. 1. General oil-droplet model of lipoproteins is presented for chylomicron, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) structures. Apolipoproteins in the outer phospholipid membrane, designated by letters, are defined in Table II. The major differences between the lipoproteins are the size of the neutral lipid (triglyceride and esterified cholesterol) core, liquid composition in the core, and apolipoprotein composition. (E) Triglycerides, ( Q ) phospholipids, and ( -) esterified cholesterol are shown. Although not shown, unesterified cholesterol is found predominantly in the phospholipid monolayer.

Vitamins K and Kj are absorbed by an active process in the proximal small intestines. Bile of normal composition is necessary to facilitate the absorption. The bile component principally concerned in the absorption and transport of fat-soluble vitamin K from the digestive tract is thought to be Jcoxycholic acid. The molecular compound of vitamin K with deoxycholic acid was effective on oral administration to rats with biliary fistula. Vitamin K is absorbed through the lymph in chylomicrons. It is tran.sportcd to the liver, where it is concentrated, but no significant storage occurs. 

Approximately 95% of total lipids of LD from bovine heart are constituted by TAG. The amount of protein present in these LD is about 5% of total mass, and the amount of phospholipids varies from 3 to 7% of total lipid. The major phospholipids forming the monolayer of these LD are phosphatidylcholine (ca. 50%) and phosphatidylethanolamine (30-40%). The NEFA content is very low. The chemical composition of LD in beef heart with their high TAG content and the rather small amount of phospholipids resembles the composition of chylomicrons. A striking difference, however, is the lack of cholesterol and cholesteryles-ters in LD from beef heart whereas these lipid species occur at approximately 1-2% of total lipid in chylomicrons. Furthermore, the protein content of LD is two to three times higher than of chylomicrons. In contrast to bovine heart LD, those of stellate cells from the rat liver consist of retinylesters, TAG, free cholesterol and a small amount of phospholipids [142]. A general characteristic of LD regardless of the cell type appears to be the content of approximately 5% phospholipids of the total mass (reviewed in Ref. [143]). 

The laws of mass action govern the interactions of lipids and most apoproteins in lipoproteins, so that as the affinities between surface components change dining lipoprotein metabolism, apoproteins may dissociate from one particle and bind to another. In fact, all of the apoproteins, with the possible exception of apoprotein B (apo B), can change their lipoprotein associations. The reason for the unique behavior of apo B remains a mystery. On the basis of their principal transport function, lipoproteins may be divided into two classes according to the composition of their major core lipids. The principal triacylglycerol carriers are chylomicrons and very-low-density lipoproteins (VLDLs), whereas most cholesterol transport occurs via LDLs and HDLs. 

A chylomicron or VLDL whose composition is optimized for lipolysis by LPL contains 10-20 molecules of apo C2/molecule of apo B. Titration of apo C2 levels against the rate of lipolysis has shown that no more than two or three apo C2 molecules per particle are needed for maximal TG hydrolysis rates. As lipolysis begins, and the surface area of the VLDL or chylomicron decreases, apo C proteins are displaced. This feature was probably developed to ensure that constant lipolysis rates of TG-rich lipoproteins are maintained until only small amounts of substrate remain, along with its apo B, apo E, and a few apo C proteins. The end-products of chylomicron and VLDL lipolysis ( remnants ) are removed by the liver via LDL receptors and other receptors (Chapter 20). 

The lipoproteins are macromolecules with varying complexes of lipids where the hydrophobic lipid portions—cholesterol esters and triglycerides—are localized at the core of the molecules. The amphipathic surface layers surrounding the core contain the apolipoproteins and phospholipids. The lipoproteins vary in size, density, lipid composition, and apolipoprotein constituents, and they ean be classihed by size, the flotation rate determined by ultracentrifugation, or their electrophoretic mobilities. Put simply, the density of a lipoprotein particle is determined by the relative amounts of lipid and protein contained in the particle. Chylomicrons and very low density lipoproteins have the highest lipid content and the lowest protein content thus, very excessive amounts of chylomicrons float on the surface of plasma. In descending order of size, the broad lipoprotein fractions (with their electrophoretic mobility) are... 

Fat constitutes approximately 38% of the calories in the average North American diet. Of this, more than 95% of the calories are present as triacylglycerols (3 fatty acids esterified to a glycerol backbone). During ingestion and absorption, dietary triacylglycerols are broken down into their constituents and then reassembled for transport to adipose tissue in chylomicrons (see Chapter 2). Thus, the fatty acid composition of adipose triacylglycerols varies with the type of food consumed. 

Fig. 32.9. Composition of a typical chylomicron. Although the composition varies to some extent, the major component is triacylglycerol (TG). C = cholesterol CE = cholesterol ester PL = phospholipid.

It is now accepted that increased postprandial lipemia is directly related to an increased rate of progression of atherosclerosis and increased risk of CHD (50,51). The degree of postprandial hypertriglyceridemia in patients with CHD is due to impaired TG clearance after a standardized fatty meal (52). Exaggerated lipemia is common in patients with CHD, and peak lipemia may occur 8 h after the fatty meal instead of the usual 3 h. Postprandial lipemia promotes the formation of chylomicron remnants (52,53). Indeed, a diet low in fat, in particular saturated fat, reduces the levels of chylomicron remnants in humans (54). The composition of the fatty meal is also important, and fish oil fatty acids may be less Upemic (54,55). 

Murata, M., Hara, K., and Ide, T. (1994) Alteration by Diacyl-glycerols of the Transport and Fatty Acid Composition of Lymph Chylomicrons in Rats, Biosci. Biotech. Biochem. 58, 1416 1419. 

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