Chylomicrons secretion

VLDL assembly and secretion is similar to the corresponding pathway for chylomicrons. Triglycerides and cholesterol esters are packaged into the core of the lipoprotein particle. However, in contrast to intestinal chylomicron secretion, hepatocytes secrete VLDL directly into the bloodstream. In the bloodstream, VLDL is acted upon by lipoprotein lipase, delivering its triglyceride cargo to muscle and adipose tissue. The resulting VLDL remnant particle, also termed IDL (intermediate density lipoprotein), is further metabolized as discussed below. 

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). 

There are striking similarities in the mechanisms of formation of chylomicrons by intestinal cells and of VLDL by hepatic parenchymal cells (Figure 25—2), perhaps because—apart from the mammary gland—the intestine and liver are the only tissues from which particulate lipid is secreted. Newly secreted or nascent chylomicrons and VLDL contain only a small amount of apolipoproteins C and E, and the frill complement is acquired from HDL in the circulation (Figures 25—3 and 25-4). Apo B is essential for chylomicron and VLDL formation. In abetalipoproteinemia (a rare disease), lipoproteins containing apo B are not formed and lipid droplets accumulate in the intestine and 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.

HDL is synthesized and secreted from both liver and intestine (Figure 25—5). However, apo C and apo E are synthesized in the liver and transferred from fiver HDL to intestinal HDL when the latter enters the plasma. A major function of HDL is to act as a repository for the apo C and apo E required in the metabohsm of chylomicrons and VLDL. Nascent HDL consists of discoid phosphohpid bilayers containing apo A and free cholesterol. These hpoproteins are similar to the particles found in the plasma of patients with a deficiency of the plasma enzyme lecithimcholesterol acyltransferase (LCAT) and in the plasma of patients with obstructive jaundice. LCAT—and the LCAT activator apo A-I— bind to the disk, and the surface phosphohpid and free cholesterol are converted into cholesteryl esters and... 

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... 

LPL found on the endothelial surfaces of the blood capillaries) to produce chylomicron remnants, which are then removed from the circulation by specific remnant receptors located on parenchymal liver cells. VLDLs are secreted by the liver. Following their secretion in blood, VLDLs undergo metabolism in a way... 

J. Luchoomun and M. M. Hussain, Assembly and secretion of chylomicrons by differentiated Caco-2 cells. Nascent triglycerides and preformed phospholipids are preferentially used for lipoprotein assembly, J. Biol. Chem. 274 (1999) 19565-19572. 

MTP is responsible for the transfer of TGs and cholesteryl esters from the endoplasmic reticulum (ER) to lipoprotein particles (VLDL in hepatocytes in the liver and chylomicrons in endocytes in the intestine) for secretion [52]. It is a heterodimer consisting of a unique large subunit essential for lipid transfer encoded by the mttp gene and a smaller subunit, the ubiquitous ER enzyme protein disulfide isomerase [53]. 

In the enterocyte, provitamin A carotenoids are immediately converted to vitamin A esters. Carotenoids, vitamin A esters, and other lipophilic compounds are packaged into chylomicrons, which are secreted into lymph and then into the bloodstream. Chylomicrons are attacked by endothelial lipoprotein lipases in the bloodstream, leading to chylomicron remnants, which are taken up by the liver (van den Berg and others 2000). Carotenoids are exported from liver to various tissues by lipoproteins. Carotenes (such as (3-carotene and lycopene) are transported by low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), whereas xanthophylls (such as lutein, zeax-anthin, and (3-cryptoxanthin) are transported by high-density lipoproteins (HDL) and LDL (Furr and Clark 1997). 

Dietary fats are required for carotenoid uptake by intestinal cells. Fats have an important role in the continuation of the process of carotenoid absorption, because the human intestine is incapable of secreting significant quantities of chylomicrons into the bloodstream in the absence of fats (Ornelas-Paz and others 2008b). Some studies have suggested that at least 5 g/day of dietary fat are required for suitable (3-carotene absorption (West and Castenmiller 1998), whereas others suggested the consumption... 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

Chylomicrons Transport dietary triglyceride and cholesterol fiom intestine to tissues apoB-48 apoOn apoE Secreted by epithelial cells Activates lipoprotein lipase Lfptake by liver... 

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.

Figure 4.13 Uptake of bile acids in the jejunum. Bile adds (BA) and cholesterol (C) are secreted from the liver, via the bile, into the duodenum. Cholesterol is transported back into the blood, from the enterocyte, within chylomicrons. The latter enter the lymphatic system (i.e. the lacteals). Bile acids are absorbed from the jejunum into the hepatic portal vein for re-uptake into the liver.

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.

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

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