Lipids in chylomicrons

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]). 

Chylomicrons are lipoprotein complexes that carry dietary lipids (including cholesterol) from the lymph through the bloodstream. Lipids in chylomicrons are partly removed in the capillaries, yielding chylomicron remnants. Apoproteins making up chylomicrons include Apo A-I, Apo A-II, Apo B-48, Apo C-I, Apo C-II, Apo C-III (Table 18,1). 

When carbohydrates are absorbed from the intestine, they pass directly into the blood that drains via the portal vein to the liver, so it is the first major organ to gain access to these nutrients. The delivery of chylomicrons into the bloodstream in the subclavian vein, rather than into the portal vein, means that the first tissues to encounter chylomicrons are not the liver. Lipids in chylomicrons first encounter the other tissues such as the heart, skeletal muscle, and adipose tissue and these interact with other chylomicrons and lipoproteins in their/fraf pass through the blood circulation. This competition with the liver for first grab at the food supply, however, is unlikely to be a major factor in the overall distribution of fuel to cells. As the mean circulation time of blood in the human is only 1 min the chylomicron pool is rapidly distributed throughout the body. 

Classically, to measure absolute absorption the plasma area imder the curve from an intravenous dose would be compared to that caused by the feeding of an oral dose. However, the carotenoids are lipid-soluble and are normally incorporated in chylomicrons synthesised in the enterocytes, a situation that cannot be replicated and applied to studies in humans because an intravenous preparation that would behave naturally is not possible. 

Lipoprotein metabolism. Entero-cytes release absorbed lipids in the form of triglyceride-rich chylomicrons. Bypassing the liver, these enter the circulation mainly via the lymph and are hydrolyzed by extrahepatic endothelial lipoprotein lipases to liberate fatty acids. The remnant particles move on into liver cells and supply these with cholesterol of dietary origin. 

Lipoproteins are classified into five groups. In order of decreasing size and increasing density, these are chylomicrons, VLDLs (very-low-density lipoproteins), IDLs (inter-mediate-density lipoproteins), LDLs (low-density lipoproteins), and HDLs (high-density lipoproteins). The proportions of apoproteins range from 1 % in chylomicrons to over 50% in HDLs. These proteins serve less for solubility purposes, but rather function as recognition molecules for the membrane receptors and enzymes that are involved in lipid exchange. 

Apolipoproteins ( apo designates the protein in its lipid-free form) combine with lipids to form several classes of lipoprotein particles, spherical complexes with hydrophobic lipids in the core and hydrophilic amino acid side chains at the surface (Fig. 21-39a). Different combinations of lipids and proteins produce particles of different densities, ranging from chylomicrons to high-density lipoproteins. These particles can be separated by ultracentrifugation (Table 21-2) and visualized by electron microscopy (Fig. 21-39b). 

HDL may be taken up in the liver by receptor-mediated endocytosis, but at least some of the cholesterol in HDL is delivered to other tissues by a novel mechanism. HDL can bind to plasma membrane receptor proteins called SR-BI in hepatic and steroidogenic tissues such as the adrenal gland. These receptors mediate not endocytosis but a partial and selective transfer of cholesterol and other lipids in HDL into the cell. Depleted HDL then dissociates to recirculate in the bloodstream and extract more lipids from chylomicron and VLDL remnants. Depleted HDL can also pick up cholesterol stored in extrahepatic tissues and carry it to the liver, in reverse cholesterol transport pathways (Fig. 21-40). In one reverse transport path, interaction of nascent HDL with SR-BI receptors in cholesterol-rich cells triggers passive movement of cholesterol from the cell surface into HDL, which then carries it back to the liver. In a second pathway, apoA-I in depleted HDL in-... 

Correct answer = E. Chylomicrons contain a lipid core that is composed of dietary lipid and lipid synthesized in the intestinal mucosal cells. Free fatty acids are esterified primarily to 2-monoacylglycerol. forming triacylglycerol, prior to export from the intestinal mucosal cells in chylomicrons. Mixed micelles are found only in the lumen of the small intestine. 

Assembly of chylomicrons The enzymes involved in triacylglycerol, cholesterol, and phospholipid synthesis are located in Ihe smooth ER. Assembly of the apolipoproteins and lipid into chylomicrons requires microsomal triacylglycerol transfer protein (see p. 229), which loads apo B-48 with lipid. This occurs during transition from the ER to the Golgi, where the particles are packaged in secretory vesicles. These fuse with the plasma membrane releasing the lipoproteins, which then enter the lymphatic system and, ultimately, the blood. 

The plasma lipoproteins contain eight major apoproteins, the structure and function of which have recently been reviewed (5). Briefly, the primary amino acid sequence is known for five of these apoproteins. ApoB, a highly hydrophobic protein, is found in chylomicrons, VLDL and LDL. It is the major polypeptide in LDL and has been shown to be responsible, in part, for the recognition of LDL by its receptor in cultured human fibroblasts (7,10). The major polypeptides of HDL are apoA-I and apoA-II apoA-l activates lecithin cholesterol acyl transferase. In addition, studies on the cellular level suggest that apoA-I may regulate the content of the lipids in the cell membrane (8). 

A. Vost and A. Maclean, Hydrocarbon transport in chylomicrons and high density lipoproteins in rat, Lipids 79 423-435 (1984). 

The triacylglycerols in chylomicrons and LDLs circulate through the blood system the former carries dietary lipids while the latter carries... 

Apolipoprotein C-II can also be isolated from VLDL or HDL (H20, L5, N3). It contains 78 residues (J3) and has been shown by Chou-Fasman analysis to bind phospholipids (M26, M40), with three predicted helical sequences (M26). ApoC-II has attracted a great deal of attention because it activates one of the most important enzymes in plasma lipid metabolism, lipoprotein lipase, responsible for the hydrolysis of triglyceride in chylomicrons and VLDL. Sparrow and Gotto have summarized a number of studies on structure-function relationships (S52). These, taken together, indicate that there are separate functional domains in apoC-II, in that lipoprotein lipase activation is mediated by residues 55-78 and phospholipid binding by... 

Q9 Lipid in the diet is present mostly in the form of triglycerides, which are digested by pancreatic lipase to yield fatty acids and monoglycerides bile salts are also required for digestion and absorption of the dietary lipids. Bile salts interact with the fatty acids and monoglycerides in the gut lumen to form micelles, which can be absorbed by the epithelial cells. In the epithelial cell the triglyceride is resynthesized to form droplets, or chylomicrons, which enter the lacteals and are carried by the lymphatic system into the general circulation. 

Within the enterocyte, retinol is bound to cellular retinol binding protein (CRBP 11) and is esterified by lecithin retinol acyltransferase (LRAT), which uses phosphatidylcholine as the fatty acid donor, mainly yielding retinyl palmitate, although small amounts of stearate and oleate are also formed. At unphysiologically high levels of retinol, when CRBP 11 is saturated, acyl coenzyme A (CoA) retinol acyltransferase (ARAT) esterifies the free retinol that accumulates in intracellular membranes. Then the retinyl esters enter the lymphatic circulation and then the bloodstream (in chylomicrons), together with dietary lipid and carotenoids (Norum et al., 1986 Olson, 1986 Blomhoff et al., 1991 Green et al., 1993 Harrison and Hussain, 2001). 

Because vitamin E is transported in lipoproteins secreted hy the liver, the plasma concentration depends to a great extent on total plasma lipids. Erythrocytes may also he important in transport, because there is a relatively large amount of the vitamin in erythrocyte membranes, and this is in rapid equilibrium with plasma vitamin E. There are two mechanisms for tissue uptake of the vitamin. Lipoprotein lipase releases the vitamin by hydrolyzing the tri-acylglycerol in chylomicrons and VLDL, whereas separately there is receptor-mediated uptake of LDL-bound vitamin E. Studies in knockout mice suggest that the main mechanism for tissue uptake of vitamin E from plasma lipoproteins is byway of the class B scavenger receptor (Mardones et al., 2002). 

The major lipid components of chylomicrons and VLDL are triacylglycerol, whereas the predominant lipids in LDL and HDL are cholesterol and phospholipids respectively. The protein part of lipoprotein is known as apoprotein. Lipoproteins occur in milk, egg-yolk and also as components of cell membranes. 

Some drugs may be absorbed into the lymphatic circulation through the lacteal or lymphatic vessels under the microvilli. Absorption of drugs through the lymphatic system bypasses the first-pass effect due to liver metabolism, because drug absorption through the hepatic portal vein is avoided. The lymphatics are important in the absorption of dietary lipids and may be partially responsible for the absorption for some lipophilic drugs such as bleomycin or aclarubicin which may dissolve in chylomicrons and be systemi-cally absorbed via the lymphatic system. 

Figure 4.44 depicts the relationship between lipoprotein lipase and the FFAs liberated from TGs in chylomicrons and VLDLs in the plasma. The enzyme is represented by black squares. The FFAs are packaged into TGs within the cell which are deposited in a lipid droplet. 

Conversion of VLDLs to VLDL Remnants in the Bloodstream HDLs and the Cycling of Cholesterol Lipids in Lipoproteins Studies on the Behavior of Lipoproteins Appearance of Chylomicrons in the Bloodstream Following a Meal of Fat or Oil... 

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