Triacylglycerols chylomicron

FIGURE 24.3 (a) A duct at the junction of the pancreas and duodenum secretes pancreatic juice into the duodenum, the first portion of the small intestine, (b) Hydrolysis of triacylglycerols by pancreatic and intestinal lipases. Pancreatic lipases cleave fatty acids at the C-1 and C-3 positions. Resulting monoacylglycerols with fatty acids at C-2 are hydrolyzed by intestinal lipases. Fatty acids and monoacylglycerols are absorbed through the intestinal wall and assembled into lipoprotein aggregates termed chylomicrons (discussed in Chapter 25). 

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... 

The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules (Figure 25-1). These are oriented so that their polar groups face outward to the aqueous medium, as in the cell membrane (Chapter 14). The protein moiety of a lipoprotein is known as an apo-lipoprotein or apoprotein, constituting nearly 70% of some HDL and as litde as 1% of chylomicrons. Some apolipoproteins are integral and cannot be removed, whereas others are free to transfer to other hpoproteins. 

Chylomicron remnants Chylomicrons 45-150 <1.006 6-8 92-94 Triacylglycerol, phospholipids, cholesterol B-48, E... 

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

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. 

Triacylglycerols of Chylomicrons VLDL Are Hydrolyzed by Lipoprotein Lipase... 

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.

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). 

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 concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

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. 

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. 

TAG-CH3 and TAG-CH2-, acyl chain terminal-CH3 and bulk (-CH2-)n groups, respectively, of fatty acids (predominantly triacylglycerols) associated with chylomicron- and very low-density lipoprotein (VLDL) Thr, threonine-CHs Val, valine-CHs. The asterisk In spectrum (b) denotes a radiolytically-generated 2.74 p.p.m. 

Chylomicron 99 80-95 2-6 3-9 1 Transport of fat absorbed in the intestine to the liver and adipose tissues (exogenous triacylglycerol)... 

Figure 4.10 Monoacylglycerol pathway for synthesis of triacylglycerol and formation of chylomicrons within the enterocyte.

Figure 4.11 Detaib of the formation of a chylomicron and its structure. Triacylglycerol is synthesised upon the smooth endoplasmic reticulum, chylomicrons are synthesised in the cytosol and then secreted into the lacteal via the Golgi.

Triacylglycerol (i) chylomicrons (ii) very low density lipoproteins intestine (diet) liver adipose tissue, muscle, lactating mammary gland... 

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.

The packaging of triacylglycerol into chylomicrons or VLDL provides an effective mass-transport system for fat. On a normal Western diet, approximately 400 g of triacylglycerol is transported through the blood each day. Since these two particles cannot cross the capillaries, their triacylglycerol is hydrolysed by lipoprotein lipase on the luminal surface of the capillaries (see above). Most of the fatty acids released by the lipase are taken up by the cells in which the lipase is catalytically active. Thus the fate of the fatty acid in the triacylglycerol in the blood depends upon which tissue possesses a catalytically active lipoprotein lipase. Three conditions are described (Figure 7.23) ... 

Figure 7.23 Fate of blood triacylglycerol (in the chylomicrons and VLDL) in three conditions role of changes in activity of lipoprotein lipase in directing the uptake of fatty acids. It is primarily the activity of Lipoprotein lipase that directs which tissue/organ takes up the fatty acids from the blood triacylglycerol. The abbreviation LPLT indicates a change to a higher activity of lipoprotein lipase LPL-i indicates a change to a lower activity of lipoprotein lipase. The broadness of the arrow indicates the dominant direction of the fate of the fatty acid.

Triacylglycerol in the forms of chylomicrons or very low density lipoproteins constitutes the mass transport system of fat in the blood. Excessive levels, particularly of VLDL, can give rise to various pathological problems which are grouped together under the title lipoproteinaemias and are discussed in Chapter 11 (Appendix 11.9). 

Cholesterol ester transfer protein catalyses the transfer of triacylglycerol from VLDL or chylomicrons to LDL and to HDL. However, it is the removal of this triacylglycerol from LDL and HDL, which occurs in the liver, via hepatic lipase, that causes problems small and dense LDL particles, which are more atherogenic than normal... 

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 the mucosal cells, long-chain fatty acids are resynthesized by an ATP-dependent ligase [5] to form acyl-CoA and then triacylglycerols (fats see p. 170). The fats are released into the lymph in the form of chylomicrons (see p. 278) and, bypassing the liver, are deposited in the thoracic duct—i. e., the blood system. Cholesterol also follows this route. 

The chylomicrons take care of the transport of triacylglycerols from the intestine to the tissues. They are formed in the intestinal mu-... 

VLDLs, IDLs, and LDLs are closely related to one another. VLDLs formed in the liver (see p. 312) transport triacylglycerols, cholesterol, and phospholipids to other tissues. Like chylomicrons, they are gradually converted into IDL and LDL under the influence of lipoprotein lipase [1]. This process is also stimulated by HDL. Cells that have a demand for cholesterol bind LDL through an interaction between their LDL receptor and ApoB-100, and then take up the complete particle through receptor-mediated endocytosis. This type of transport is mediated by depressions in the membrane ( coated pits"), the interior of which is lined with the protein clathrin. After LDL binding, clathrin promotes invagination of the pits and pinching off of vesicles ( coated vesicles"). The clathrin then dissociates off and is reused. After fusion of the vesicle with ly-sosomes, the LDL particles are broken down (see p. 234), and cholesterol and other lipids are used by the cells. 

This enzyme [EC 3.1.1.34] (also called clearing factor lipase, diglyceride lipase, and diacylglycerol lipase) catalyzes the hydrolysis of a triacylglycerol to produce a diacylglycerol and a fatty acid anion. This enzyme hydrolyzes triacylglycerols in chylomicrons and in low-density lipoproteins and also acts on diacylglycerols. See also Lipases... 

The triacylglycerols and cholesteryl esters form the hydrophobic core of the chylomicrons, which are coated with surface phospholipids, free cholesterol, and apolipoprotein B-48. 

B. The triacylglycerols of chylomicrons are degraded to FFAs and glycerol in many tissues, but especially in skeletal muscle and adipose tissue. 

Triacylglycerols are incorporated, with cholesterol and apolipoproteins, into chylomicrons. 

The fatty acids of triacylglycerols furnish a large fraction of the oxidative energy in animals. Dietary triacylglycerols are emulsified in the small intestine by bile salts, hydrolyzed by intestinal lipases, absorbed by intestinal epithelial cells, reconverted into triacylglycerols, then formed into chylomicrons by combination with specific apolipoproteins. 

Chylomicrons deliver tiiacylglycerols to tissues, where lipoprotein lipase releases free fatty acids for entry into cells. Triacylglycerols stored in adipose tissue are mobilized by a hormone-sensitive triacylglycerol lipase. The released fatty acids bind to serum albumin and are carried in the blood to the heart, skeletal muscle, and other tissues that use fatty acids for fuel. 

Chylomicrons, discussed in Chapter 17 in connection with the movement of dietary triacylglycerols from the intestine to other tissues, are the largest of the lipoproteins and the least dense, containing a high... 

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