Bile salt micelles structure

This paper reports the systematic study of the apparent anhydrous micellar weights of the three principal bile salts found in man and their glycine and taurine conjugates in respect to bile salt concentration, counterion concentration, temperature, pH, and urea concentration. On the basis of these studies, model structures of bile salt micelles are proposed. Sodium dehydrocholate, a triketo bile salt, was also studied but was not found to form micelles. 

Many studies have been carried out on the micellar size of bile salt micelles (3, 4,12,13,17, 20, 25). The experimental conditions and results have been tabulated in a recent review 15). Because these studies were carried out with different bile salts in different laboratories using different techniques at different temperatures, pH, and salt concentrations, values have ranged from monomers (4) to aggregates having nearly 1000 associated molecules (12). This has tended to confuse investigators interested in biological and biochemical aspects of bile salts, who wanted to know the size of the bile salt micelle. The emphasis here is that the type of bile salt, the pH, the temperature, and the counterion concentration all can affect the size and probably the structure of bile salt micelles. 

The effect of low concentrations of urea (2M) on the large dihydroxy bile salt micelles is striking, while similar concentrations have no effect on the small trihydroxy or dihydroxy micelles. The effects of urea on micelle formation and aggregate size are undoubtedly complicated (10) and involve changes in solvent structure and thus hydrophobic bonding and hydration of polar groups. For large micelles of dihydroxy bile salt... 

An alternative proposal might be that bile salts elongate in ribbonlike structures with increased counterion concentration. These micelles would be very asymmetric. However, in all previous studies where the shape of the bile salt micelles has been studied (11) it appeared to be almost spherical. This tends to rule out an elongated ribbon-like structure. 

In hPL Winkler et al. (1990) originally suggested that the amides of Leu-154 (structurally equivalent to 145 in RmL) and Phe-78 may make up the oxyanion hole, van Tilbeurgh et al. (1993) succeeded in the structural characterization of a complex of hPL with bovine procolipase (see Section III,C for the description of this cofactor and its function) crystallized in the presence of mixed phospholipid/bile salt micelles. In this complex hPL assumes the active conformation, and it is clear that after the accompanying conformational change the amides of Leu-154 and Phe-78 can indeed serve as electrophiles for the oxyanion. 

G. Bile Salt Micelle Size and Shape — Effects of Structure, Concentration, Counterion, pH, Temperature, Urea, and Other Solvents... 

Fig. 47. Comparison of proposed structure of primary and secondary bile salt micelles and a classical detergent micelle (43). (A, C) Longitudinal and cross sections of primary and secondary bile salt micelles, respectively. (B) Ordinary detergent micelles. Top— Orientation of molecules at oil-water interface (refer to Section V). Wavy line—Hydrocarbon chains of detergent molecules. Shaded area—Lipidsoluble cyclic hydrocarbon part of bile salt molecule. Polar head of detergent molecule. OH or ester groups. Negatively charged ionic group of bile salt.

Fig. 56. Cholesterol-sodium cholate-water ternary phase diagram. The structure of the bile salt micelles is indicated in the inset. These micelles remain small in the presence of cholesterol (Section IX. E). It will be noted that the micellar zone is smalt and that no liquid crystalline phases are formed in this system (2, 6, 47).

Based on experimental data and theoretical considerations[25-27], the suggested role of the bile salt micelle is to overcome the "resistance" of the UWL to lipid diffusion across the microvillar membrane. There is, however, little evidence to suggest that this "resistance" is differentially affected by trihydroxy bile salt-containing micelles, as opposed to micelles containing dihydroxy bile salts. Thus, although an (UWL) may limit sterol diffusion at the mucosal cell surface, there does not appear to be a major specifictiy of a unique bile salt structure in modifying the resistance of this barrier. 

Figure 4.33 Model for the structure of bile salt micelles. From Small [82] with permission.

Ekwall and Baltcheffsky [265] have discussed the formation of cholesterol mesomorphous phases in the presence of protein-surfactant complexes. In some cases when cholesterol is added to these solutions a mesomorphous phase forms, e.g. in serum albumin-sodium dodecyl sulphate systems, but this does not occur in serum albumin-sodium taurocholate solutions [266]. Cholesterol solubility in bile salt solutions is increased by the addition of lecithin [236]. The bile salt micelle is said to be swollen by the lecithin until the micellar structure breaks down and lamellar aggregates form in solution the solution is anisotropic. Bile salt-cholesterol-lecithin systems have been studied in detail by Small and coworkers [267-269]. The system sodium cholate-lecithin-water studied by these workers gives three paracrystalline phases I, II, and III shown in Fig. 4.37. Phase I is equivalent to a neat-soap phase, phase II is isotropic and is probably made up of dodecahedrally shaped lecithin micelles and bile salts. Phase III is of middle soap form. The isotropic micellar solution is represented by phase IV. The addition of cholesterol in increasing quantities reduces the extent of the isotropic... 

The structure of cholic acid helps us understand how bile salts such as sodium tauro cholate promote the transport of lipids through a water rich environment The bot tom face of the molecule bears all of the polar groups and the top face is exclusively hydrocarbon like Bile salts emulsify fats by forming micelles m which the fats are on the inside and the bile salts are on the outside The hydrophobic face of the bile salt associates with the fat that is inside the micelle the hydrophilic face is m contact with water on the outside... 

McKenna et al. (1977) found that a bis steroid [10] can bind perylene without micellization. Interestingly, the corresponding monosteroid did not bind perylene in the absence of micellization. The bis-steroid may assume a conformation which is related to the aggregate structure of bile salts. An... 

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