Bile salts physical properties

Carey, M. C. 1983. Measurement of the physical-chemical properties of bile salt soluticBite brads in bastroenterology, edited by Barbara, L., et al., 19 Boston MTP Press. 

Numerous surface-active molecules have been studied as GI absorption promoters in a wide variety of testing conditions, including model membranes, everted intestinal sacs, tissue cultures, intestinal epithelia in diffusion chambers, intact animals, and humans. The physical properties of a chemical enhancer may be strongly dependent on the interactions with the endogenous GI components such as bile salts, pH, and bacteria. Thus the in vitro experiments on enhancing GI absorption are not necessarily predictive of the behavior of the promoter in animals or humans, and we will mainly focus on summarizing results from in vivo studies. 

G. F. Martin, C. Marriott, and L W. Keiiaway. Direct effect of bile salts and phospholipids on the physical properties of mucus. Cut /9 103-110 (1978). 

Over 50 methods have been employed in the literature to determine CMC values of bile salt solutions (reviewed in [6]). These can be divided into two broad categories (a) methods requiring no physical or chemical additive in the bulk solution and (b) methods involving the use of an additive in the bulk solution. The former methods, also called non-invasive, include surface tension and the measurements of a variety of colligative bulk properties (conductivity, turbidimetry, osmometry, self-diffusion, refractive index, modal volumes, electrometric force) or electromagnetic bulk properties (NMR, sound velocity and adsorption, etc.), all as functions of bile salt concentration. The second set of methods, also called invasive, depends upon a change in some physical or chemical property of an additive which occurs with the formation of micelles. These include the spectral change of a water-soluble dye, micellar solubilization of a water-insoluble dye, interfacial tension at liquid-liquid interfaces, and partition coefficients between aqueous and immiscible non-polar phases. Whereas a detailed discussion of the merits and demerits of both approaches can be found elsewhere [6], non-invasive methods which are correctly utilized provide the most reliable CMC values. 

The relative content of the dietary fat components varies with different sources but generally the physico-chemical properties are rather similar. For absorption to take place the physico-chemical properties of the fat have to be changed. This takes place as a consequence of the lipolytic activity in the intestinal tract and the addition of bile to chyme. Through lipolytic enzymes the dietary lipids are converted to more polar products. Bile contributes bile salt-phospholipid-cholesterol aggregates to the intestinal content (cf. Chapter 13). The concerted action of these agents is the formation of lipid products in a physical state which allows them to be transported into the enterocyte membrane and onwards for further metabolism in the cell. Bile salts are involved in the proper function of some of these enzymatic reactions and in the formation of product phases on which a normal uptake process is based. Little is known at present of the importance of bile salts for the intracellular reactions following uptake of fat into the enterocyte. Different aspects of intestinal lipid absorption have been reviewed in recent years by Patton [7], Thomson and Dietschy [8], Carey [9], Carey et al. [10], Wells and Direnzo [11], and Grundy [12]. The role of bile acids in fat absorption has been discussed by Holt [13]. 

Noninvasive delivery of insulin via most mucosal membranes requires the use of chemical enhancement for notable insulin absorption (see Section 3.3 and Table II). However, most permeation enhancers have, in addition to their effect on the mucosal membrane, an often pronounced influence on insulin three-dimensional structures. Thus, sodium salicylate (Touitou et al, 1987) as well as bile salts (Gordon etal, 1985) have been shown to dissociate insulin oligomers into monomers. This effect improves membrane permeability, but it may also reduce the physical stability and increase the susceptibility of insulin to enzymatic degradation. The exposure of new epitopes may also influence the immunological properties of the insulin formulation. 

Therefore, I shall concentrate on only those bile acids that have been reasonably well studied from a physicochemical point of view and which have some relation to physiology and biochemistry of living things. Because the specific physical characteristics of the bile acids and their alkaline metal salts vary considerably with the number of hydroxyl groups present on the steroid nucleus, I will present a fairly detailed description of the physicochemical properties of cholanic acid (no hydroxyl groups), monohydroxy, dihydroxy, and trihydroxy bile acids. Since the triketo bile acid (dehydrocholic acid) has been used widely as a choleretic, its properties will also be discussed. Unfortunately, many interesting bile acids and bile alcohols isolated from a variety of vertebrates (29-32) have not been studied physicochemical ly. However, knowing their molecular structure, many of the properties of these compounds can be deduced by comparison with the known properties of bile acids discussed in this chapter. 

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