Fatty acid-monoglyceride micelles

A micellar phase is formed in the intestinal lumen when the bile salt concentration exceeds the critical micellar concentration (approximately 3-4 mM). This concentration of bile salts is usually exceeded during normal digestion. Mixed micelles contain bile salts, fatty acids, monoglycerides, cholesterol, and other lipid-soluble molecules (including fat-soluble vitamins) and are considered to be the major route of delivery of the products of fat digestion to the absorptive mucosal cell. Other nonmicellar phases may coexist in the intestinal lumen with the micellar phase these include an oil phase and a viscous isotropic phase. 

Within the small intestine, bile-acid binding interferes with micelle formation. Nauss et al. [268] reported that, in vitro, chitosan binds bile acid micelles in toto, with consequent reduced assimilation of all micelle components, i.e., bile acids, cholesterol, monoglycerides and fatty acids. Moreover, in vitro, chitosan inhibits pancreatic lipase activity [269]. Dissolved chitosan may further depress the activity of lipases by acting as an alternative substrate [270]. 

Fatty acids [25], monoglycerides [25], fatty acid-bile salt micelles [26], and surfactants [27] have all been shown to increase epithelial membrane permeability by affecting the membrane proteins or lipids [28]. 

Q9 Lipid in the diet is present mostly in the form of triglycerides, which are digested by pancreatic lipase to yield fatty acids and monoglycerides bile salts are also required for digestion and absorption of the dietary lipids. Bile salts interact with the fatty acids and monoglycerides in the gut lumen to form micelles, which can be absorbed by the epithelial cells. In the epithelial cell the triglyceride is resynthesized to form droplets, or chylomicrons, which enter the lacteals and are carried by the lymphatic system into the general circulation. 

The possible use of mixed micelles (e.g., made of unsaturated fatty acids and monoglycerides) has been shown for the enhanced rectal absorption of several compounds, including a and p interferon and insulin. 

The 2-monoglycerides and fatty acids are packaged into micelles (solubilized by bile salts) and absorbed into intestinal epithelial cells, where they are reconverted to triacylglycerols. 

In response to a meal, cholecystokinin is released from the intestine and causes relaxation of the sphincter of Oddi and contraction of the gallbladder (see Chapter 48). This allows a concentrated solution of micelles (consisting of bile salts, lecithin, and cholesterol) to enter the intestine. In the intestinal lumen, dietary cholesterol and the products of triglyceride digestion (predominantly free fatty acids and monoglycerides) are incorporated into mixed micelles. Micelles deliver lipolytic products to the mucosal surface. To carry out these functions, a critical micellar bile acid concentration of 2ramoI/L is necessary. 

Hayes, D. G. and Gulari, E., 1-Monoglyceride production from lipase-catalyzed esterification of glycerol and fatty acid in reverse micelles, Biotechnol. Bioeng., 38, 507-517, 1991. 

In an earlier review [3], mixed micelles formed by bile salts were classified into those with (i) non-polar lipids (e.g., linear or cyclic hydrocarbons) (ii) insoluble amphiphiles (e.g., cholesterol, protonated fatty acids, etc.) (iii) insoluble swelling amphiphiles (e.g., phospholipids, monoglycerides, acid soaps ) and (iv) soluble amphiphiles (e.g., mixtures of bile salts with themselves, with soaps and with detergents) and the literature up to that date (1970) was critically summarized. Much recent work has appeared in all of these areas, but the most significant is the dramatic advances that have taken place in our understanding of the structure, size, shape, equilibria, and thermodynamics of bile salt-lecithin [16,18,28,29,99-102,127, 144,218,223,231-238] and bile salt-lecithin-cholesterol [238,239] micelles which are of crucial importance to the solubihty of cholesterol in bile [1]. This section briefly surveys recent results on the above subclasses. Information on solubilization, solubilization capacities or phase equilibria of binary, ternary or quaternary systems or structures of liquid crystalline phases can be found in several excellent reviews [5,85,207,208,210,211,213,216,217] and, where relevant, have been referred to earlier. 

Fat-soluble vitamins such as retinol and )3-carotene are readily dissolved in mixed lipid-bile salt micelles in vitro. Retinol is approximately 10 times more readily dissolved in such micelles than /3-carotene [105]. It is likely that these two substances occupy different regions of the micelle. The difference in solubility, therefore, may reflect the limited capacity of the nonpolar core of the micelle for the relatively bulky /3-carotene molecule. Retinol, on the other hand, may occupy a more hydrophilic region of the micelle. In a mixed oil/micellar system, a-tocopherol distributes between the two phases, its concentration in the micellar phase being enhanced by expansion of the micelles with monoglycerides and lecithin of long-chain fatty acids. However, lipids containing medium-chain fatty acids do not expand the micelles as effectively as their long-chain counterparts such that there is less solubilization of a-tocopherol in the micellar phase [106]. 

Stages of lipid digestion in the intestinal tract. Step 1 is the emulsification of fat droplets by bile salts. Step 2 is the hydrolysis of triglycerides in emulsified fat droplets into fatty acids and monoglycerides. Step 3 involves dissolving fatty acids and monoglycerides into micelles to produce "mixed micelles."... 

Through the detergent action of the bile salts, the monoglycerides and fatty acids produced hy lipase action are incorporated in micelles (Chemistry VIII), which are able to cross the brush border of the intestine into the mucosal cells. 

The available data indicate that the hypocholesterolemic and hypolipidemic activity of chitosan is probably due to disruption and/or inhibition of micelle formation. At pH 6.0-6.5 chitosan begins to precipitate and as the linear chains of the polysaccharide start to aggregate, they can entrap the whole micelles. The entrapped cholesterol, fatty acids and monoglycerides thus escape absorption. Such "polar entrapment," shown in Figure 2, can occur in the duodenum. Another mode of action could be the "disintegration" of mixed micelles, which can start before the precipitation of chitosan, and in which the free fatty acids and bile acids are selec-... 

In the small intestine, pancreozymin causes the gallbladder to contract, and bile, a micellar solution of bile acids, lecithin, and cholesterol, is secreted into the duodenum. Pancreozymin also causes discharge and continued synthesis of pancreatic lipase which adsorbs to the oil-water interface, liberating 2-monoglycerides and fatty acids (76). Whether bile acids adsorb to the interface and if so how they spatially orient with respect to lipolytic products and lipase is unknown. At concentrations below the CMC, bile acids will adsorb to monolayers of lipolytic products (77), but no information is available on the interaction of bile acid solutions above their CMC with monolayers of lipolytic products. Somehow, the lipolytic products are transferred to the bulk phase, where they form mixed micelles with bile acid molecules (Fig. 14). 

Fig. 14. Schematic depiction of selected physical and chemical events during fat digestion. The 1- and 3-ester linkages of triglyceride (upper left) are cleaved by lipase, forming 2-monoglyceride and fatty acid. These lipolytic products leave the oil-water interface and are dispersed in the aqueous phase as mixed bile acids-lipolytic product micelles. A proposed molecular arrangement of the bile acid-lipolytic product micelle is shown in cross-section this model is based on studies of the bile acid-lecithin micelle (65). In this model, the hydrophobic back of the bile acid molecule apposes the paraffinic chains of the lipolytic products, and the hydroxy groups of the bile acid molecule are toward the aqueous phase. The paraffin chains of the interior of the micelle are liquid, thus permitting other water-insoluble molecules such as cholesterol and fat-soluble vitamins to dissolve in the micelle. Indeed, the solvent capacity of the bile acid-lipolytic product micelle is contributed chiefly by the paraffin chains of the lipolytic products.

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