Chylomicrons Lipoproteins

Fat-emulgated preparations for parenteral administration have been elaborated for clinical applications. Since these are administered to the patients intravenously, the size of fat emulsion particles should not exceed the size of the largest naturally occurring lipoproteins-chylomicrons, i.e. about I fiin. Fat emulsions on the basis of com oil (preparation lipomaize), cottonseed oil (lipofundin, lipomol). 

Dietary cholesterol, together with triacylglycerols, is absorbed from the intestinal tract and enters the large lipoprotein chylomicrons (see Fig. 21-1). Absorption of cholesterol is incomplete, usually amounting to less than 40% of that in the diet. Absorption requires bile salts and is influenced by other factors.186 As it is needed cholesterol is taken from the plasma lipoproteins into cells by endocytosis. Much of the newly absorbed cholesterol is taken up by the liver. The liver also secretes cholesterol, in the form of esters with fatty acids, into the bloodstream. 

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. 

FIG. 2 Transport of cholesterol (CHOL) and plant sterols (PS) in the enterocyte. CHOL, PS, and other lipids are solubilized in micelles that deliver the lipids to the brush border membrane. CHOL and PS are transported into the enterocyte by NPC1L1. Nearly all of the PS are redirected back to the intestinal lumen by the transporters ABCG5 and ABCG8. The extent to which CHOL is transported by ABCG5 and ABCG8 is not known. CHOL within the enterocyte is packaged into lipoproteins (chylomicrons) and secreted into lymph and eventually the bloodstream for transport to the liver. 

Primary chylomicronemia (familial lipoprotein Chylomicrons, VLDL Dietary management Niacin plus fibrate... 

Abetalipoproteinemia (ABL) is a rare, autosomal recessive disease first described by Bassen and Kornsweig in 1950. It is characterized by the absence of plasma apoB lipoproteins, fat-soluble vitamin deficiencies (A, E, and K), and the presence of acanthocytosis (Table 27-1). Other signs include fat malabsorption presenting as steatorrhea, flatus, abdominal discomfort, and progressive ataxic neuropathy. The key diagnostic feature is an extremely low plasma total cholesterol and absence of all apoB lipoproteins (chylomicrons, VLDL, and LDL). 

Absence of plasma apoB lipoproteins (chylomicrons, VLDL, and LDL)... 

ABL) recessive lipoproteins particle fat-soluble vitamin deficiencies, spinocerebellar disease, retinitis pigmentosa, acanthocytosis, galee blanche intestine, fatty liver apoB lipoproteins (chylomicrons, VLDL, and LDL)... 

Although apoE was recognized first as a component of VLDLs (Shore and Shore, 1973 Shelburne and Quarfordt, 1974 Utermann, 1975 Kane et al., 1975), it has been demonstrated to be present in most other lipoprotein classes as well. In addition to occurring in the other triglyceride-rich lipoproteins, chylomicrons and their remnants, and the intermediate-density lipoproteins (IDEs), apoE is present in a subclass of the cholesterol-rich high-density lipoproteins (HDLs), referred to as HDL-with apoE (Mahley, 1978). By use of SDS-PAGE (Fig. 6), the Mr 34,200 apoE is easily distinguished from the other common apolipoproteins that also are present in the various human lipoprotein classes. 

Vertebrate, especially mammalian, lipoproteins have been extensively studied. In the invertebrate world, only insect lipoproteins have received serious attention. Whereas vertebrates rely on a battery of lipoproteins (chylomicrons, very low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins) to effect lipid transport, insects use primarily a single type of lipoprotein, lipophorin, for lipid transport. Lipophorin is both more versatile than vertebrate lipoproteins in terms of the diverse lipids it transports and more efficient than vertebrate lipoproteins in that, for the most part, it delivers lipids to tissues without being internalized and destroyed. We believe that new insights can be obtained from an understanding of insect lipoproteins, and in this article we review the current state of knowledge about the structure and metabolism of lipophorins. 

Given the very large size of LPL substrate lipoproteins (chylomicrons and VLDLs) and the complex series of events involved in their remodeling in the course of lipolysis, it is... 

ApoE plays a major role in the metabolism of triglyceride-rich lipoproteins (chylomicrons, chylomicron remnants, VLDL, and IDL) and in the local redistribution of lipids among cells. About half of the plasma apoE in fasting subjects is associated with triglyceride-rich lipoproteins the other half is a constituent of HDL. 

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. 

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. 

Apart from the predominant lymphatic drug absorption mechanism, other possible mechanisms of drug transport through intestinal barriers include transcellular and paracellular absorption of drug molecules, inhibition of P-gp and/or CYP450 to accumulate the intracellular drug concentration, and production of lipoprotein/ chylomicron. 

A specific type of interaction between lipids and proteins is found in lipoproteins which transport triglycerides and cholesteryl esters in the plasma of mammalians. The largest lipoproteins, chylomicrons with a diameter between 800 A and 5000 A, and very-low-density lipoproteins (VLDL), with a diameter of 300-800 A, resemble emulsion droplets with a core of non-polar lipid and a surface coat of phospholipids and proteins (cf. Brown et ai, 1981). A physical characterization of chylomicrons has been reported (Parks et al.y 1981). Most of the plasma cholesterol occurs in low-density lipoprotein (LDL) which is a particle with a diameter of 200 A. The core consists of almost pure cholesteryl esters and a surface coat of a phospholipid monolayer and four tetrahedrally arranged apoproteins (Gulik-Krzywicki et aly 1979). The smallest particle, high-density lipoprotein (HDL), is a kind of molecular lipid-protein complex. 

The enzymes for phosphatidate synthesis, acyl CoA synthetase, glycerol 3-phosphate acyltransferase and monoacylglycerol acyltransferase, are on both the outer mitochondrial membrane and the endoplasmic reticulum membrane. Diacylglycerol acyltransferase is only on the endoplasmic reticulum it may use either diacylglycerol phosphate synthesized on the endoplasmic reticulum or that synthesized on the mitochondrion. Triacylglycerol synthesized on the endoplasmic reticulum membrane may then enter lipid droplets either in the cytosol or, in the liver and intestinal mucosa, the lumen of the endoplasmic reticulum for assembly into lipoproteins - chylomicrons in the intestinal mucosa (section 4.3.2.2) and very low-density lipoprotein in the liver (section 5.6.2). 

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