Bile salts crystalline structures

Biochemically, a change in structure relating to the mucopolysaccharides (neuraminic add ) and monohydroxy bile acids probably accounts for the formation of biliary thrombi. Some of the under-hydroxylated bile salts appear in crystalline form the bile becomes increasingly viscous and its flow is impeded. This defect in the excretion of bile salts culminates in dysfunctions in the secretion of bilirubin, which is why bilirubin is regurgitated into the blood. The bile which accmnulates in the bile ducts ultimately becomes mucous and white because of the reabsorption of bile pigments by the epitheha of the small bile ducts. 

This hitherto neglected area is now receiving major attention and the crystalline structures of many common and uncommon bile acids [43,44,48,49], their alkaline and alkaline metal salts [7,51,53] have been defined. Choleic acids have been the subject of much activity in this field. A summary of the earlier work on choleic acids can be found in Sobotka [42] and Small [5]. 

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. 

The crystalline structure of cholanic acids and their alkaline metal salts has unfortunately been neglected. The major crystallographic work was carried oUt by Kratky, Giacomello, and co-workers (76-79) 30 years ago and was oriented toward solving the structure of the choleic acids. These substances, isolated by Wieland and Sorge (80), are mixed crystals of deoxy-cholic acids (or certain other bile acids such as a and apocholic acids) obtained on crystallization from organic solvents. A summary of the work on choleic acid appears in Sobotka (28). 

The structures of certain uncommon bile acids and their ethyl esters have abo been studied (79, 81), and incomplete crystal data of certain bile acid derivatives given in a brief note (72). The crystalline structures of most of the common bile acids and their alkaline salts have not yet been defined. 

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).

Fig. 60. Sodium oleate-sodium cholate-water ternary-phase diagram. Expressed as wt%. The various phases have been numbered I-V. The lamellar liquid crystalline phase can incorporate little bile salt into the lattice. The micellar phase is large and includes all possible combinations of sodium oleate and sodium cholate, provided the amount of water is sufficient. The structure of these micelles is not yet known, but see Section IX.C (42). 37 C, pH 9.0.

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