Bile salt mixed micelles with phospholipids

Although bile salts possess a polar head group, the hydrocarbon tail usually contains polar hydroxyl groups. Therefore the rigid ring system gives a tightly packed, almost solid, nonpolar phase rather than a liquid one. However, like cholesterol, bile salts can form mixed micelles with phospholipids. 

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. 

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... 

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. 

Taurocholate is able to form micelles infusion of TC has been shown [232] to increase output of phospholipid and cholesterol with which it forms mixed micelles. Dehydrocholate has a low tendency to micelle formation and has little influence on the biliary excretion of cholesterol and phospholipid. However, Hardison and Apter [233] have found that while micelle formation is an important factor in the biliary excretion of lipids, it cannot alone explain the results they have obtained. Dehydrocholate, a synthetic agent, is a potent choleretic presumably because its osmotic activity in bile is not diminished by micelle formation and it may therefore exert an osmotic force in biliary canaliculae approximately equal to its concentration. As a result, bile flow is increased more by this substance than by micelle-forming bile salts. Some metabolites of dehydrocholate are, however, capable of micelle formation [234,235]. 

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