Mixed micelles lipid transport

Solubilization of lipid digestion products in intestinal mixed micelles enhances their dissolution and dramatically increases the GI lumen-enterocyte concentration gradient that drives absorption by means of passive diffusion. Micelles, however, are not absorbed intact [8, 9], and lipids are thought to be absorbed from a monomolecular intermicellar phase in equilibrium with the intestinal micellar phase [10], The dissociation of monomolecular lipid from the micellar phase appears to be stimulated by the presence of an acidic microclimate associated with the enterocyte surface [11,12], In addition to passive diffusion, growing evidence suggests that active uptake processes mediated by transport systems located in the enterocyte membrane are also involved in the absorption of (in particular) fatty acids into the enterocyte [4],... 

The main advantage of paraceUular transport is the low proteolytic activity present in the paraceUular pathway. Lipid-surfactant mixed micelles enhance the... 

When taken orally, it follows the same route as that of other dietary lipids. It is part of the mixed micelles and ends up on the chylomicrons formed in the intestinal mucosa cells. It is then transported to the hver on the chylomicron remnants where, like the endogenously produced cholecalciferol from sunlight, it is hydroxylated to 25- OH-cholecalciferol. 

The enterocytes of the small intestine can be isolated and used for study of intracellular aspects of intestinal lipid transport like triglyceride synthesis [52]. The disappearance of the mucus barrier during isolation of the epithelial cells results in plasma membrane disintegration and loss of cellular integrity when the cells are exposed to bile salts. As is the case for brush border vesicles, the system of isolated cells does not allow study of interaction between enterocytes and lipids dispersed in a form that resembles physiological conditions, i.e. solubilized in mixed bile salt micelles. 

A detailed investigation of the effect of micellar solubilization on the transport of lipids has been made by Westergaard and Dietschy [59]. They studied in vitro uptake of lipids into rabbit intestinal disks by varying the proportions of lipid and bile salts in mixed micelles in 3 different ways. Either lipid concentration was increased with bile salts kept at a constant level, lipid concentration was unchanged while bile salt concentration was varied, or both lipid and bile salt concentration was increased with the molar ratio kept constant. Theoretical calculations of how the mass of the lipid probe was distributed between the aqueous and the micellar compartment showed that there was a good correlation between calculated aqueous monomer concentration and experimentally obtained values for lipid uptake. The rate of uptake is thus proportional to the aqueous monomer concentration of a particular lipid. The conclusion drawn was that diffusion of the lipid molecules in monomeric form through the aqueous phase is an obligatory step before uptake into the plasma membrane, and that the role of bile salt is therefore to overcome the resistance of the unstirred water layer by micellar solubilization. 

Data on absorption of non-micellar lipids in the presence of bile salts is available from the study )y Knoebel [79]. The lymphatic transport of absorbed oleic acid and site of uptake from the intestinal lumen was measured in bile fistula rats. It was found that the concentration of bile salts in a continuous intraduodenal infusion did not affect the steady-state level of lipid appearing in the lymph until the bile salt concentration was as low as 1 mM, which represented a molar ratio of 20 1 of lipid to bile salt. In the case of infusates with relatively low concentrations of bile salts it was found that a larger part of the available surface area of the small intestine was utilized. The main conclusion is that lipids are equally well absorbed in vivo from non-micellar dispersions of lipids and bile salts as from solutions where the lipids are completely solubilized by bile salt mixed micelles. However, a detailed analysis of kinetics of uptake from non-micellar phases in vitro with isolated intestinal segments has not yet been done. 

During the process of absorption, cholesterol dissolved in the lipid core of micelles is transported from the lumen of the small intestine across the intestinal wall and into the lymph. Because the solubility of cholesterol in aqueous systems is low, its absorption depends on the formation of detergent structures (mixed micelles) in the small intestine. These are composed mainly of bile salts, phospholipids, digestion products of fats such as fatty acids and monoacylglycerols, cholesterol (of which 90% is in free form), and fat-soluble micronutrients (Figure 6). 

Figure 7. Mixed micelles carry the solubilized hydrophobic lipids through the aqueous digest medium into close proximity with the intestinal mucosal cells (enterocytes). Micelles are not absorbed intact, but the various components are taken up by the enterocytes at independent rates. Intracellular esterification of cholesterol by acyl-coenzyme A prevents its transport back to the intestinal lumen. After esterification, cholesterol esters are assembled into chylomicrons and secreted into the lymjiiatic system and, finally, to the blood circulation.

Vitamin E, an apolar molecule that is the most important lipid-soluble antioxidant in humans, is not synthesized in our body, but it is acquired by nourishment. Vitamin E is emulsified together with the fat-soluble components of the food and transported in the body. Lipolysis and emulsification of the formed lipid droplets then lead to the spontaneous formation of mixed micelles [61]. 

Recent physical-chemical observations on native mammalian systems reveal that the proposed mixed micellar mechanism of lipid solubilization and transport in both bile and in upper small intestinal contents is incomplete [1,260-263]. Bile is predominantly a mixed micellar solution but, particularly when supersaturated with Ch, also contains small liquid-crystalline vesicles which, as suggested from model systems [239], are another vehicle for Ch and L transport. In dog bile which is markedly unsaturated with Ch [258], these vesicles exist in dilute concentrations and may be markers of the detergent properties of BS on the cells lining the biliary tree and/or related to the mode of bile formation at the level of the canaliculus. In human hepatic bile, which is generally dilute and markedly supersaturated with Ch, these vesicles may be the predominant form of Ch and L solubilization and transport [261]. If hepatic bile is extremely dilute, it is theoretically possible that no BS-L-Ch micelles may be present [268] all of the lipid content may be aggregated... 

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