Small intestine lipoproteins

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). 

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... 

The answer is a. (Katzung, p 590.) Bile acids are absorbed primarily in the ileum of the small intestine. Cholestyramine binds bile acids, preventing their reabsorption in the jejunum and ileum. Up to 10-fold greater excretion of bile acids occurs with the use of resins. The increased clearance leads to increased cholesterol turnover of bile acids. Low-density lipoprotein receptor upregulation results in increased uptake of LDL. This does not occur in homozygous familial hypercholesterolemia because of lack of functioning receptors. 

Hydrolysis of retinyl ester to retinol occurs in the lumen of the small intestine from where it is absorbed with the aid of bile salts, esterified to form retinyl ester and then released into lymph where it is incorporated into chylomicrons. The action of lipoprotein lipase converts chylomicrons to remnants and the retinyl ester remains in the remnants to be taken up by the Uver, where it is stored as the ester until required. On release from the liver, it is transported in blood bound to retinal binding-protein. 

The fourth major lipoprotein type, high-density lipoprotein (HDL), originates in the liver and small intestine as small, protein-rich particles that contain relatively little cholesterol and no cholesteryl esters (Fig. 21-40). HDLs contain apoA-I, apoC-I, apoC-II, and other apolipoproteins (Table 21-3), as well as the enzyme lecithin-cholesterol acyl transferase (LCAT), which catalyzes the formation of cholesteryl esters from lecithin (phosphatidylcholine) and cholesterol (Fig. 21-41). LCAT on the surface of nascent (newly forming) HDL particles converts the cholesterol and phosphatidylcholine of chylomicron and VLDL remnants to cholesteryl esters, which begin to form a core, transforming the disk-shaped nascent HDL to a mature, spherical HDL particle. This cholesterol-rich lipoprotein then returns to the liver, where the cholesterol is unloaded some of this cholesterol is converted to bile salts. 

Plasma Lipoproteins. The plasma lipids are transported by four major lipoprotein classes. The plasma lipoproteins are synthesized and secreted only in the intestine and liver. Chylomicrons, the richest in triglyceride, are synthesized in the small intestine and transport dietary (exogenous) triglyceride and cholesterol. Very low density (prebeta) lipoproteins (VLDL)... 

FIG. 1 Movement of cholesterol (CHOL) and bile acids (BA) between the liver and small intestine. CHOL and BA in the liver are secreted into the gallbladder where they are stored temporarily until a fat-containing meal causes their secretion into the intestinal lumen. BA are absorbed with high efficiency (95%) and are recycled back to the liver via the hepatic portal vein. CHOL is absorbed less efficiently (50-60%) and must be incorporated into lipoproteins (chylomicrons) for transport back to the fiver via the systemic circulation. Accumulation of CHOL in the liver can promote secretion of CHOL into plasma, thus increasing LDL-CHOL concentration. Loss of CHOL and BA in feces represents the primary route of CHOL elimination from the body. 

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 newly synthesized triacylglycerol becomes organized into chylomicrons (a type of lipoprotein see next section), which are secreted by the intestinal epithelial cell into the lacteals, small lymph vessels in the villi of the small intestine. Then from the lymphatics, the chylomicrons pass into the thoracic duct, from which they enter the blood and thus contribute to the transport of lipid fuel to various tissues. A feature of chylomicron metabolism is their ability to deliver lipid fuels to extrahepatic tissues. 

Chylomicrons are produced from dietary fat by the removal of resynthesised triglycerides from the mucosal cells of the small intestine into the intestinal lumen. These then enter the circulation via the thoracic dncts in the lymphatic system and enter into the subclavian veins, where triglyceride content is reduced by the action of lipoprotein lipases (LPL) on capillary endothelial surfaces in skeletal muscle and fat. The free fatty acids (FFA) from the triglycerides are used by the tissues as an energy source or stored as triglycerides. The chylomicron remnants, stripped of triglyceride and therefore denser, are then taken up by the liver by LDL receptor-mediated endocytosis, thereby delivering cholesterol to the liver. 

Phylloquinone is absorbed in the proximal small intestine, by an energy-dependent mechanism, and is incorporated into chylomicrons. Estrogens increase phylloquinone absorption in both male and female animals, and male animals are more susceptible to dietary vitamin K deprivation than females (loUy et al., 1977). Even after an overnight fast, about half the plasma vitamin K is present in chylomicron remnants, and only a quarter in low-density lipoprotein. The plasma concentration of phylloquinone is associated with genetic variants of apoprotein E, which determines the binding of chylomicron remnants to the liver lipoprotein receptor (Kohlmeier et al., 1996). 

Lipoproteins are macromolecules comprising proteins (= apolipoproteins, apoproteins) and lipids. They transport water-insoluble lipids in the blood, with the exception of the albumin-bound free fatty acids. Only short-chain fatty acids are dissolved in plasma. The lipoproteins are formed in the liver and in the mucosa of the small intestine. (14)... 

Very low density lipoproteins (VLDL) are synthesized in the liver cell at the contact area of the smooth and rough endoplasmic reticulum and, to a very minor degree, in the mucosa of the small intestine. They have a particle size of 30-80 nm and consist of 90% lipids and 8 — 13% proteins. Their density is <1.006 g/ml. The predominant apohpoproteins are B, C III, and E. They are designated as pre-beta lipoproteins on the basis of their electrophoretic migration. The main function of VLDL is the transport of triglycerides of endogenous origin, (s. fig. 3.8)... 

High density lipoproteins (HDL2.3) are formed in the liver and small intestine. A minor proportion of the HDL appears to derive from triglyceride-rich lipoproteins in the plasma. HDL have a particle size of 5-15 nm and appear initially as disk-shaped bodies which, after uptake of lipids and lipoproteins, develop in the blood to spherically shaped molecules. They comprise ca. 50% hpids and 45-55% proteins. Their density is <1.21 g/ml. They are designated... 

Special proteins, called apoLipoproteins, are required for handling and traruv port of lipid droplets. These proteins are synthesized on the ER and enter the lumen of the ER, where they are assembled into large macromolecular structures. The relevant proteins include apolipoprotein A apo A) and apo lipoprotein B (apo B), Apo A and apo B combine with lipid droplets to form structures called chylomicrons, microscopic particles with large cores of lipid coated with a thin shell of protein. The chylomicrons are transferred to secretory vesicles, which migrate through the cytoplasm to the basal membrane of the cell. Here the vesicles fuse with the membrane, resulhng in the expulsion of chylomicrons from the cell. (If the vesicles fused with the apical membrane of the enterocyte, the effect would be a futile transfer of the dietary lipids back to the lumen of the small intestine.)... 

Lipoproteins are assembled in two organs, the small intestine and the liver. The lipoproteins assembled in the intestine contain the lipids assimilated from the diet. These lipoproteins, called chylomicrons, leave the enterocyte and enter the bloodstream via the Lymphatic system. The lipoproteins assembled in the liver contain lipids originating from the bloodstream and from de novo synthesis in the liver. The term de novo simply means "newly made from simple components" as opposed to "acquired from the diet" or "recycled from preexisting complex components." These lipoproteins, called very-low-dcnslty lipoproteins (VLDLs), are secreted from the liver into the bloodstream. The liver also synthesizes and secretes other Lipoproteins called high-density Lipoproteins (HDLs), which interact with the chylomicrons and VLDLs in the bloodstream and promote their maturation and function. The data in Table 6-4 show that chylomicrons contain a small proportion of protein, whereas HDLs have a relatively high protein content. Of greater interest is the identity and function of the proteins that constitute these particles. These proteins confer specific properties to lipoprotein particles, as detailed later in this chapter. 

FIGURE 6.19 The llpopiotetn map illustrates the fact that tissues can derive energy from lipoproteins formed by cells of the gut as well as by cells of the liver (hepatocytes). The chylomicrons and VLDLs are mixed together thmu out the circulatory system. Not shown is the contribution of apo C-IJ and apo E to these particles by the HDLs, The map shows that cholesterol is taken up by the peripheral tissues from the LDl, but not to a large extent from the chylomicrons or the chylomicron remnants. The map also shows that TGs are removed from lipoproteins by lipoprotein lipase, w hereas cholesterol is removed after endocytosis of the particle. Also shown is the delivery of bile, which contains bile salts, cholesterol, and phospholipids, to the small intestine, The drawmg is stylixed and does not closely represent the anatomy,... 

The rate at which cholesterol and triglycerides enter the circulation from the liver and small intestine depends on the supply of the lipid and proteins necessary to form the lipoprotein complexes. Although the protein component must he synthesized, the lipids can be obtained either from de novo biosynthesis in the ti.ssucs or from the diet. Reduction of plasma lipids by diet can delay the development of atherosclerosis. Furthermore, the u.sc of drugs that decrease assimilation of lipids into the body plus diet decreases mortality from cardiovascular disca.se. ... 

Tocopherols and tocotrienols are believed to be absorbed to the same extent, but a tocopherol transfer protein with a specific affinity for a-tocopherol is considered responsible for the discrimination between the different E-vitamers and the selective incorporation of a-tocopherol into nascent, very-low-density lipoprotein (Hosomi et at., 1997). Other forms of vitamin E, which are discriminated during this process, are most likely excreted via the bile after shortening and carboxylation of their phytyl tails (Traber et al., 1998 Swanson et al., 1999). Recently, the biological importance of y-tocopherol has gained more attention. Because it is preferentially secreted from the liver into the small intestine via the bile duct, it may be superior to a-tocopherol in increasing the antioxidant status of digesta (Stone and Papas, 1997). When tissues are saturated with a-tocopherol, this E-vitamer is excreted via the bile to the same extent as the other vitamers (Kayden and Traber, 1993). 

The absorption of natural vitamin K from-the small intestine into the lymphatic system is facilitated by bile, as is true for other fat-soluble materials. Efibciency of absorption varies from 15% to 65% as reflected by recovery in lymph within 24 hours. Vitamins Ki and K2 are bound to chylomicrons for transport from mucosal cells to the liver. Menadione (Ks) is more rapidly and completely absorbed from the gut before entering the portal blood. In liver, intraceUular distribution is mostly in the microsomal fraction, where phenylation of menadione to form K2 occurs. Release of vitamin K to the blood stream allows association with circulating P-lipoproteins for transport to other tissue. Significant levels of vitamin K have been noted in the spleen and skeletal muscle. 

After partial hydrolysis in the gut, dietary fatty acids, monoacylglycerols, phospholipids, and cholesterol are absorbed into the mucosal enterocytes lining the small intestine (Chapter 12). Once within the cell, the lipids are reesterified and form a lipid droplet within the lumen of the smooth endoplasmic reticulum. These droplets consists of triacylglycerol and small amounts of cholesteryl esters and are stabilized by a surface film of phospholipid. At the junction of the smooth and the rough endoplasmic reticulum, the droplet acquires apoproteins B-48, A-I, A-II, and A-IV, which are produced in the lumen of the rough endoplasmic reticulum in the same way as other proteins bound for export. The lipoprotein particle is then transported to the Golgi stacks where further processing yields chylomicrons, which are secreted into the lymph and then enter the blood circulation at the thoracic duct. 

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