Blood lipoproteins chylomicrons

Lipoprotein (LPLase) is required for the metabolism of both chylomicrons and VLDL. This enzyme is induced by insulin and transported to the luminal surface of capillary endothelium where it is in direct contact with the blood. Lipoprotein lipase hydrolyzes the fiitty adds from triglycerides carried by ch)4oinicrons and VLDL and is activated by apoC-II. 

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. 

As precursors for the biosynthesis of fats (lipogenesis), the adipocytes use triacylglycerols from lipoproteins (VLDLs and chylomicrons see p. 278), which are formed in the liver and intestines and delivered by the blood. Lipoprotein lipase [1], which is located on the inner surface of the blood capillaries, cleaves these triacylglycerols into glycerol and fatty acids, which are taken up by the adipocytes and converted back into fats. 

In blood, lipids exist as lipoprotein particles, the main function of which is to transport lipids to and from various tissues and organs of the body. There is considerable interest in blood lipoproteins from the viewpoint of human health, especially obesity and cardiovascular diseases. Lipoproteins are classified into four groups on the basis of density, which is essentially a function of their triglyceride content, i.e. chylomicrons, very low density lipoprotein particles (VLDL), low density lipoprotein (LDL) particles and high density lipoprotein (HDL) particles, containing c. 98, 90, 77 and 45% total lipid, respectively (Figure 3.11). 

Blood plasma contains a number of soluble lipoproteins, which are classified, according to their densities, into four major types. These lipid-protein complexes function as a lipid transport system. Isolated lipids are insoluble in blood, but they are rendered soluble, and therefore transportable, by combination with specific proteins, the so-called lipoproteins. There are four basic types in human blood (1) chylomicrons, (2) very low density lipoproteins (VLDL), (3) low-density lipoproteins (LDL). and (4) high-density lipoproteins (HDL). Their properties are summarized in Table 6.2. 

Lipoproteins transport hydrophobic fats in plasma (Fig. 13-2). The major lipoproteins (Chap. 6) circulating in the blood are chylomicrons, VLDLs (very low density lipoproteins), LDLs (low-density lipoproteins), and HDLs (high-density lipoproteins). IDLs (intermediate density lipoproteins) are derived from VLDLs in the formation of LDLs. Fatty acids are important cellular... 

The major classes of blood lipoproteins include chylomicrons, VLDL, IDL, LDL, and HDL. 

Chylomicrons are the least dense of the blood lipoproteins because they have the most triacylglycerol and the least protein. 

B. Because chylomicrons contain the most triacylglycerol, they are the least dense of the blood lipoproteins. VLDL is more dense than chylomicrons. Because LDL is produced by degradation of the triacylglycerols of VLDL, LDL is more dense them VLDL. HDL is the most dense of the blood lipoproteins. 

D. Chylomicrons are blood lipoproteins produced from dietary fat. VLDL are produced mainly from dietary carbohydrate. IDL and LDL are produced from VLDL. 

Two types of lipoproteins, chylomicrons and VLDL, are produced in the fed state. The major function of these lipoproteins is to provide a blood transport system for triacylglycerols, which are very insoluble in water. However, these lipoproteins also contain the lipid cholesterol, which is also somewhat insoluble in water. The triacylglycerols of chylomicrons are formed in intestinal epithelial cells from the products of digestion of dietary triacylglycerols. The triacylglycerols of VLDL are synthesized in the liver. 

Triacylglycerols, the major dietary lipids, are digested in the lumen of the intestine (Fig. VI.4). The initial digestive products, free fatty acids and 2-monoacylglyc-erol, are reconverted to triacylglycerols in intestinal epithelial cells, packaged in lipoproteins known as chylomicrons (so they can safely enter the circulation), and secreted into the lymph. Ultimately, chylomicrons enter the blood, serving as one of the major blood lipoproteins. 

Because of their high triacylglyc-erol content, chylomicrons are the least dense of the blood lipoproteins. When blood is collected from patients with certain types of hyperlipoproteinemias (high concentrations of lipoproteins in the blood) in which chylomicron levels are elevated, and the blood is allowed to stand in the refrigerator overnight, the chylomicrons float to the top of the liquid and coalesce, forming a creamy layer. 

Cholesterol is packaged in chylomicrons in the intestine and in very-low-den-sity lipoprotein (VLDL) in the liver. It is transported in the blood in these lipoprotein particles, which also transport triacylglycerols. the triacylglycerols of the blood lipoproteins are digested by lipoprotein lipase, chylomicrons are converted to chylomicron remnants, and VTDT is converted to intermediate-density lipoprotein (IDL) and subsequently to low-density lipoprotein (LDL). These products return to the liver, where they bind to receptors in cell membranes and are taken up by endocytosis and digested by lysosomal enzymes. LDL is also endocy-tosed by nonhepatic (peripheral) tissues. Cholesterol and other products of lysosomal digestion are released into the cellular pools. The liver uses this recycled cholesterol, and the cholesterol that is synthesized from acetyl CoA, to produce VLDL and to synthesize bile salts. 

The best-characterized lipoprotein receptor, the LDL receptor, specifically recognizes apoB-100 and apo E. Therefore, this receptor binds VLDL, IDL, and chylomicron remnants in addition to LDL. The binding reaction is characterized by its saturability and occurs with high affinity and a narrow range of specificity. Other receptors, such as the LDL receptor-related proteins (LRP) and the macrophage scavenger receptor (notably types SR-Al and SR-A2, which are located primarily near the endothelial surface of vascular endothelial cells), have broad specificity and bind many other ligands in addition to the blood lipoproteins. 

The lipoprotein triacylglycerols in chylomicrons and VLDL are hydrolyzed to fatty acids and glycerol by lipoprotein lipase (LPL), an enzyme attached to endothelial cells of capillaries in muscle and adipose tissue. The enzyme found in muscle, particularly heart muscle, has a low for these blood lipoproteins. Therefore, it acts even when these lipoproteins are present at very low concentrations in the blood. The fatty acids enter muscle cells and are oxidized for energy. The enzyme found in adipose tissue has a higher and is most active after a meal when blood lipoprotein levels are elevated. 

The free FA and MAG are absorbed by the enterocytes of the intestinal wall and absorbed Upids are transported in water-soluble form to other tissues. FA with chain lengths shorter than 14 carbon atoms are bound to albumin and preferentially transported directly to the liver via the portal vein. Only a smaU proportion of MCFA undergoes a conversion to LCFA and esterified to TAG. A very small fraction of LCFA is transported via the portal route. This fraction increases when long-chain TAGs are fed in combination with medium-chain TAGs. The absorbed hpid fractions consist of FA, 2-MAG, some 1-MAG, lyso PL, some PL, fat-soluble vitamins, and small amounts of glycerol and cholesterol. The first step in mucosal transport is reesterification, and the second step is the synthesis of transport particles the so-called lipoprotein (chylomicron) and very low-density lipoproteins (VLDL). They enter the bloodstream via the lymph vessels. Lipoprotein hpase located on the interior walls of the capillary blood vessels hydrolyzes the TAG, releasing FA. These enter... 

The apolipoproteins, along with the lipids which are bonded over hydrophilic interactions, form the. so-called lipoproteins. Chylomicrons are responsible for the uptake in the blood and tran.spori of the fat contained in food. In the blood apolipoprolein Cll is taken up from high-density lipoproteins (HDLsl which are activated by the lipoprotein lipase. With their help the fats are hydrolyzed in the chylomicrons. The free fatty acids are now available for the body cells or bind with the albumins of the blood. The remaining particles are completely degraded in the liver. 

Figure 25-2. The formation and secretion of (A) chylomicrons by an intestinal cell and (B) very low density lipoproteins by a hepatic cell. (RER, rough endoplasmic reticulum SER, smooth endoplasmic reticulum G, Golgi apparatus N, nucleus C, chylomicrons VLDL, very low density lipoproteins E, endothelium SD, space of Disse, containing blood plasma.) Apolipoprotein B, synthesized in the RER, is incorporated into lipoproteins in the SER, the main site of synthesis of triacylglycerol. After addition of carbohydrate residues in G, they are released from the cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system. VLDL are secreted into the space of Disse and then into the hepatic sinusoids through fenestrae in the endothelial lining.

Heart Pumping of blood Aerobic pathways, eg, P-oxidation and citric acid cycle Free fatty acids, lactate, ketone bodies, VLDL and chylomicron triacylglycerol, some glucose Lipoprotein lipase. Respiratory chain well developed. 

A schematic representation of the metabolism of lipoproteins is shown in Fig. 12 [170]. Chylomicrons are synthesized and secreted by the small intestine. They are hydrolyzed in blood by the enzyme lipoprotein lipase... 

Hyperlipoproteinemia, Type V. This pathology is manifested by increased con-tents of chylomicrons, pre-P-lipoproteins, triglycerides, and cholesterol in the patients blood plasma. 

Figure 7.4 Fate of triacylglycerol that is present in fuel blood after secretion by the intestine. The dietary triacylglycerol in the intestine is hydrolysed to long-chain fatty acids and monoacyl-glycerol, both of which are taken up by the enterocytes in which they are then re-esterified. The triacylglycerol is released in the form of chylomicrons into the blood, from where it is hydrolysed to fatty acids and glycerol by the enzyme lipoprotein lipase in specific tissues (Figure 7.3). The fatty acids are taken up by adipocytes, muscle fibres and secretory cells in the mammary gland.

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