Bile acids physical properties

Nonmodified silica gel is used most commonly for the separation of substances of medical interest. The separation is based on the interactions (hydrogen bonding, van der Waals forces, and ionic bonding) between the molecules of drugs, lipids, bile acids, etc., and the silica gel. Alumina has similar properties but is rarely used. Successful separation of endogenous substances, drugs, or their metabolites can also be achieved using physically or chemically modified silica gel. 

Quantitatively, the most important bile acid microbial transformation of cholic and chenodeoxycholic acid is the 7a-dehydroxylation yielding the secondary bile acids deoxycholic acid and lithocholic acid, respectively. The 7 -dehydroxylation alters markedly the physical properties and physiological effects of the bile acid molecule. There is a decrease in the solubility of secondary bile acids in aqueous solutions and an alteration of the critical micellar concentration (Chapter 13). 

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]. 

Publication of a book devoted entirely to the chemistry, physiology, and metabolism of bile acids indicates a renascence in interest in these poly-functional detergents. Here we will summarize present views on the physical and physiological properties of bile acids in relation to their chemical structure which bear on their participation in the intestinal absorption of fat, their enterohepatic circulation, and their influence on electrolyte and water absorption by the colon. Several of these topics are considered in detail elsewhere in this book, as well as in recent reviews (1-4). This chapter will focus on our own studies but will also emphasize areas in which information is needed. 

In addition to changing the physical properties of bile acids, conjugation also alters their physiological properties. On the basis of extremely limited evidence, it seems likely that the bile acid pool of animals with exclusively taurine conjugates is maintained chiefly by active absorption from the ileum. 

In this section, we shall consider the last three items, i.e., the surface and bulk interactions of lipolytic products with bile acids. We shall concentrate on the dispersion of lipolytic products in micellar form by bile acid solutions. This subject is complex and difficult to present clearly because it involves the physical chemistry of surface and bulk properties, which has received relatively little attention from physical chemists. We have termed the events occurring during fat digestion as physicochemical events because the chemical events influence and are influenced by the physical properties of the participating molecules. 

Several other atypical acids were eventually isolated from various species. Ursodeoxycholic acid, first isolated in crystalline form from bear bile in 1927 (58), was identified as the 7/S-epimer of chenodeoxycholic acid. The so-called /3-hyodeoxycholic acid (3 3,6a), which Kimura obtained in small amounts from pig bile (59), was structurally identified in the course of a thorough investigation of the four possible 3,6-dihydroxycholanic acids (60). The lagodeoxycholic acids isolated from rabbit bile by Kishi (61) were not characterized until the recent studies of Danielsson et al. (62) identified one of these compounds as allodeoxycholic acid. The contention that one of them may have been the 12 -epimer of deoxycholic acid was placed in doubt by Koechlin and Reichstein (63), who prepared that acid and found that it did not exhibit the physical properties of the natural material. 

A. Some Physical Properties of Bile Acids and Their Amino Acid Conjugates... 

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. 

The finding that water-soluble flavonoids could exert their beneficial properties at the hydrophobic portion of the membrane was also observed in in vivo studies and in cells in culture. For example, erythrocytes obtained from animals fed a flavanol- and procyanidin-rich meal showed reduced susceptibility to free-radical-mediated hemolysis [Zhu et al., 2002]. Consistently, we demonstrated that procyanidin hexamers, which interact with membranes but would not be internalized, protected Caco-2 cells from AMVN- and bile-induced oxidation [Erlejman et al., 2006]. When liposomes were preincubated with a series of flavonoids with diverse hydrophobicity, not only hydrophobic flavonoids prevented AMVN-mediated lipid oxidation but also the more hydrophilic ones [Erlejman et al., 2004]. Similarly to what was previously found in liposomes, the protective effects of flavonoids against AMVN-supported oxidation was strongly associated with their capacity to prevent membrane disruption by detergents, supporting the hypothesis of a physical protection of membranes by preventing oxidants to reach fatty acids. 

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