Bile Salt-Lecithin Micelles

Using phase equilibrium techniques (discussed in Section X) it was shown that bile salts are extremely efficient solubilizers of lecithin (2, 4). 

Critical Micellar Concentration (CMC) of NaTC-Lecithin Micelles in Different NaCl Concentrations, pH 6.9, 20 °C 

Molar ratio NaTCilecithin CMC, mmoles bile salt per liter  

Increasing numbers of lecithin molecules give a disc of larger area having an increasing diameter (Z x). The perimeter of the disc will increase by JkDi, exposing an increased surface to be covered by bile salts. As the perimeter is increased by approximately 8 A two more bile salts (one each for upper and lower part of the bilayer) will be needed. The sum of the number of lecithin 

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MA Schwarz, K Raith, HH Ruettinger, G Dongowski, RHH Neubert. Investigations of interactions between drugs and mixed bile salt/lecithin micelles—a characterization by micellar affinity capillary electrophoresis. Part III. J Chro-matogr A 781 377-389, 1997. 

The electrophoretic mobilities of C-labeled cholic, deoxycholic, and chenodeoxycholic acid and their corresponding taurine and glycine conjugates were determined by Norman (42). The paper electrophoresis was performed in barbiturate buffer of ionic strength 0.1, pH 8.6, in an electric field of 7.5 V/cm for 3 hr. When 1 pg of each acid, as the sodium salt dissolved in 25 pi of water, was applied to the paper strips, the isotope determination after electrophoresis showed broad peaks all with a mean mobility similar to that of albumin or slightly lower. The electrophoretic mobilities of all of the bile acids were influenced by the concentration in the solution applied and presented difficulties in identifying bile acids in natural extracts. The migration of bile salt-lecithin micelles on paper electrophoresis has been reported by Shimura (43). The micelles were prepared by addition of lecithin to mixed bile salts, which may have also contained cholesterol. 

NA Mazer, GB Benedeck, MC Carey. Quasielastic light-scattering studies of aqueous biliary lipid systems. Mixed micelles formation in bile salt-lecithin solutions. Biochemistry 19 601-615, 1980. 

K Muller. Structural aspects of bile salt-lecithin mixed micelles. Hepatology 4 134S-137S, 1984. 

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. 

Nichols JW and OzarowskiJ. Sizing of Lecithin-Bile Salt Mixed Micelles by Size-Exclusion High-Performance Liquid-Chromatography. Biochemistry 1990 29 4600-4606. 

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. 

Fig. 17. Longitudinal and cross-sectional views of the proposed molecular models for the structure of bile salt-lecithin (BS-L) mixed micelles. All recent experimental data for BS-swelling amphiphile micelles are consistent with model B. In this model, reverse BS aggregates are present in high concentrations within the hydrophobic domains of L or other swelling amphiphile bilayers. BS also coat the perimeter of the disks as a bilayered ribbon . (From ref. 102 with permission.)...

Bile is a mixed micellar solution of bile salt-lecithin-cholesterol which on dilution forms aggregates of much larger size than micelles indicating the formation at the phase limits of liposome-like bodies [9]. In intestinal content during lipid digestion in man, saturated mixed micelles and vesicles or liposomes containing the... 

In the lumen of the small intestine, dietary fat does not only meet bile salt but the much more complex bile in which bile salts are about half saturated with lecithin in a mixed micellar system of bile salt-lecithin-cholesterol. On dilution in the intestinal content, the micelles grow in size as the phase limit is approached and large disk-like micelles form which fold into vesicles [49]. These changes are due to the phase transition that occurs when the bile salt concentration is decreased and the solubility limit for lecithin in the mixed micelles is exceeded. The information is mostly derived from in vitro studies with model systems but most probably is applicable to the in vivo situation. What in fact takes place when the bile-derived lamellar bile salt-lecithin-cholesterol system meets the partly digested dietary fat can only be pictured. Most probably it involves an exchange of surface components, a continuous lipolysis at the interphase by pancreatic enzymes and the formation of amphiphilic products which go into different lamellar systems for further uptake by the enterocyte. Due to the relatively low bile salt concentration and the potentially high concentration of product phases in intestinal content early in fat digestion, the micellar and monomeric concentration of bile salt can be expected to be low but to increase towards the end of absorption. 

The aggregation behavior of C21-DA salt in dilute electrolyte medium appears to resemble that of certain polyhydroxy bile salts (25,16). That C21-DA, with a structure quite different from bile acids, should possess solution properties similar to, e.g., cholic acid is not entirely surprising in light of recent conductivity and surface tension measurements on purified (i.e., essentially monocarboxylate free) disodium salt aqueous solutions, and of film balance studies on acidic substrates (IX) The data in Figure 3 suggest that C21-DA salt micelles Incorporate detergents - up to an approximate weight fraction of 0.5 -much like cholate Incorporates lecithin or soluble... 

P Schurtenberger, NA Mazer, W Kanzig. Micelle-to-vesicle transition in aqueous solution of bile salt and lecithin. J Phys Chem 89 1042-1049, 1985. 

Miller et al have reported that in bile salt solutions in the presence of EL, if the EL concentration is less thcin half of that of the bile salts, the mixed micelle shape beccmes spherical, but, otherwise, the shape is a disk as shown in Figure 2. All solutions used here inclixie 32 mM lecithin and 100 mM total bile salts, therefore the micelle shape in all systems here must be spherical. Edward et al... 

Figure 2 The mixed micelles consisting of Bile salts and Lecithin. Disk Excess Lecithin. Sphere Excess Bile salts.

Vahouny, G.V., Tombes, R., Cassidy, M.M., Kritchevsky, D., and Gallo, L.L. 1981. Dietary fibres. VI. Binding of fatty acids and monolein from mixed micelles containing bile salts and lecithin. 

The possible reasons for the different behavior of natural surfactants could include the following. Natural surfactants lead to surface tension values higher than those corresponding to the same concentration of a synthetic surfactant. The ability to nullify the aqueous layer resistance could be related with the surface tension values. However, the micelles of bile salts are smaller and more rigid than the micelles of synthetic surfactants. The solubilization potential of bile salts is increased in the presence of lecithins and fatty acids. For instance, the absorption rate constants obtained in the presence of sodium taurocholate and glycocholate mixed-micelles with lecithin for a series of acids were significantly lower than those obtained in the presence of simple micelles of the same bile salts [29, 30]. 

Bile salts are produced in the liver and secreted into the intestinal lumen forming mixed micelles with lecithin, monoglycerides, fatty adds and cholesterol. Because... 

Bile salts readily form mixed micelles with lipid-like molecules such as lecithins or fatty acids. These mixed micelles are structurally very different from the simple micelles and generally have a much greater solubilizing capacity for hydrophobic molecules, both biological and synthetic. The solubility of DDT, a non-polar, water insoluble molecule, for example, in bile salt micellar solution can be increased to a far greater extent by the addition of unsaturated long chain fatty acids, probably because of mixed micelle formation. 

Fic. 2. Schematic diagrams of bile salt micelles (A) or mixed micelles (B), showing die molecular arrangement of bile salts and lecithin. The closed circles represent nonionic polar groups, and the open circles represent ionic polar groups of the molecules. [Redrawn from ref. (M20) with permission from Biochemistry 19. Copyri t (1980) American Chemical Society.]... 

The classic X-ray diffraction work of Small et al. [5,207,208] pointed out the existence of inverted (reverse) bile salt micelles within mixed bile salt-phospholipid liquid crystalline bilayers. The aggregates were considered to consist of 2-4 molecules (of cholate) with their hydrophilic sides facing inwards bound by hydrogen bonds between the hydroxyl groups, leaving their hydrophobic sides facing outwards to interact with the acyl chains of the phospholipid. At saturation, about 1 molecule of cholate was present for every 2 molecules of lecithin. Appreciably more bile salts... 

The classic biological example of these systems is bile salt (BS)-lecithin (L)-cholesterol (Ch) micelles which have been studied in detail by QLS [239], In TC-L-Ch systems, particle size and polydispersity were studied as functions of Ch mole fraction (= 0-15%), L/TC molar ratio (0-1.6), temperature (5-85°C), and total lipid concentration (3 and 10 g/dl) in 0.15 M NaCl. For values below the established solubilization limits (A )> added Ch has little influence on the size of simple TC micelles, on the coexistence of simple and mixed TC-L micelles, or on the growth of mixed disk TC-L micelles. For supersaturated systems >1), 10 g/dl simple micellar systems (L/TC = 0) exist as metastable micellar solutions even at = 5.3. Metastability is decreased in coexisting systems... 

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